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

ANGIOPLASTY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N...

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ANGIOPLASTY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Angioplasty: 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: 0-597-84334-1 1. Angioplasty-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on angioplasty. 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 ANGIOPLASTY ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Angioplasty................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND ANGIOPLASTY ............................................................................... 111 Overview.................................................................................................................................... 111 Finding Nutrition Studies on Angioplasty................................................................................ 111 Federal Resources on Nutrition ................................................................................................. 116 Additional Web Resources ......................................................................................................... 116 CHAPTER 3. ALTERNATIVE MEDICINE AND ANGIOPLASTY ......................................................... 119 Overview.................................................................................................................................... 119 National Center for Complementary and Alternative Medicine................................................ 119 Additional Web Resources ......................................................................................................... 126 General References ..................................................................................................................... 128 CHAPTER 4. DISSERTATIONS ON ANGIOPLASTY........................................................................... 129 Overview.................................................................................................................................... 129 Dissertations on Angioplasty..................................................................................................... 129 Keeping Current ........................................................................................................................ 130 CHAPTER 5. CLINICAL TRIALS AND ANGIOPLASTY ..................................................................... 131 Overview.................................................................................................................................... 131 Recent Trials on Angioplasty..................................................................................................... 131 Keeping Current on Clinical Trials ........................................................................................... 137 CHAPTER 6. PATENTS ON ANGIOPLASTY ..................................................................................... 139 Overview.................................................................................................................................... 139 Patents on Angioplasty.............................................................................................................. 139 Patent Applications on Angioplasty .......................................................................................... 167 Keeping Current ........................................................................................................................ 202 CHAPTER 7. BOOKS ON ANGIOPLASTY ......................................................................................... 203 Overview.................................................................................................................................... 203 Book Summaries: Federal Agencies............................................................................................ 203 Book Summaries: Online Booksellers......................................................................................... 204 Chapters on Angioplasty............................................................................................................ 208 CHAPTER 8. PERIODICALS AND NEWS ON ANGIOPLASTY ........................................................... 211 Overview.................................................................................................................................... 211 News Services and Press Releases.............................................................................................. 211 Newsletter Articles .................................................................................................................... 215 Academic Periodicals covering Angioplasty .............................................................................. 216 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 219 Overview.................................................................................................................................... 219 U.S. Pharmacopeia..................................................................................................................... 219 Commercial Databases ............................................................................................................... 220 Researching Orphan Drugs ....................................................................................................... 220 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 225 Overview.................................................................................................................................... 225 NIH Guidelines.......................................................................................................................... 225 NIH Databases........................................................................................................................... 227 Other Commercial Databases..................................................................................................... 229 APPENDIX B. PATIENT RESOURCES ............................................................................................... 231

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Overview.................................................................................................................................... 231 Patient Guideline Sources.......................................................................................................... 231 Finding Associations.................................................................................................................. 235 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 237 Overview.................................................................................................................................... 237 Preparation................................................................................................................................. 237 Finding a Local Medical Library................................................................................................ 237 Medical Libraries in the U.S. and Canada ................................................................................. 237 ONLINE GLOSSARIES................................................................................................................ 243 Online Dictionary Directories ................................................................................................... 244 ANGIOPLASTY DICTIONARY ................................................................................................. 245 INDEX .............................................................................................................................................. 325

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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 angioplasty 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 angioplasty, 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 angioplasty, 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 angioplasty. 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 angioplasty, 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 angioplasty. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON ANGIOPLASTY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on angioplasty.

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

Renal Vascular Disease: Medical Management, Angioplasty, and Stenting Source: Seminars in Nephrology. 20(5): 474-488. September 2000. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: In the absence of adequate research trials, there remains great debate concerning the best management of patients with renal (kidney) vascular disease. This debate is compounded by the fact that these patients do not represent a homogenous group; different causes and presentations of the disease each carry a different prognosis and potential response to therapy. Treatment options include medical management (including drug therapy), surgery, or percutaneous approaches (angioplasty or stenting). This review article examines the results of observational studies of medical

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and percutaneous therapies for blood pressure control and preservation of kidney function. Generally, in patients with fibromuscular disease, the results of percutaneous management are superior to medical therapy. Although these observational studies are difficult to compare, in patients with atheromatous disease, the results with interventional and medical therapy appear roughly similar. There have been three randomized prospective trials of routine angioplasty versus medical management. These trials show little advantage to interventional therapies in those patients whose blood pressure is well controlled with medication who do not show progression of renal insufficiency during medical management. Based on these data, this review outlines a potential management strategy that relies on an individualized risk benefit assessment. In most cases, there is ample time to consider all options, and hasty decisions should be avoided. Blood pressure can usually be at least partially controlled with medication in the short term, and even in the case of advanced renal insufficiency, a patient may benefit from a short course of hemodialysis before intervention. In each patient, the first task is to compare the likelihood of success with the risks of intervention. 1 figure. 2 tables. 106 references. •

Effect of Balloon Angioplasty on Hypertension in Atherosclerotic Renal-Artery Stenosis Source: New England Journal of Medicine. 342(14): 1007-1014. April 6, 2000. Summary: Patients with hypertension (high blood pressure) and renal artery stenosis (narrowing of the blood vessels to the kidney) are often treated with percutaneous transluminal renal angioplasty. However, the long term effects of this procedure on blood pressure are not well understood. This article reports on a study investigating the effect of balloon angioplasty on hypertension in these patients. The authors randomly assigned 106 patients with hypertension who had atherosclerotic renal artery stenosis and a serum creatinine concentration (a measure of kidney function) of 2.3 mg per deciliter or less, to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher, despite treatment with two antihypertensive drugs. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. At three months, the blood pressures were similar in the two groups; at that time, patients in the angioplasty group were taking 2.1 (plus or minus 1.3) defined daily doses of medication and those in the drug therapy groups were taking 3.2 (plus or minus 1.5) daily doses. In the drug therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. The authors conclude that, in the treatment of patients with hypertension and renal artery stenosis, angioplasty has little advantage over antihypertensive drug therapy. 1 figure. 3 tables. 24 references.

•

Periodontal Assessment of Patients Undergoing Angioplasty for Treatment of Coronary Artery Disease Source: Journal of Periodontology. 73(6): 631-636. June 2002. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225.

Studies

5

Summary: This article reports on a cross-sectional study undertaken to assess the periodontal condition of patients with coronary artery disease (CAD) in order to verify the association between CAD and certain periodontal parameters. The study include 80 patients (48 male, 32 female; aged 23 to 83 years, median age 54 years). Upon cardiac catheterization, 50 were diagnosed with severe CAD (experimental group) and 30 with no angiographic evidence of CAD (control group). Patients with CAD were divided into 3 subgroups according to the clinical diagnosis of acute infarction (AI, n = 20), stable angina (SA, n = 20), and unstable angina (UA, n = 10). The following dental, medical, and social histories were recorded: number of dental visits per year, frequency of brushing per day, and flossing per week, tobacco use, presence or absence of hypertension, diabetes, total cholesterol level, and the highest level of education completed. Periodontal parameters were also assessed for each subject. The significant confounding factors were found to be age and gender. The periodontal condition of the 80 subjects was clinically diagnosed as gingivitis or mild periodontitis, or both. Analysis of the data after adjusting for age and gender demonstrated a statistically significant association between bleeding on probing and gingival index and CAD in patients with AI; and facial or lingual clinical attachment level in patients with UA. No significant associations were found between probing depth, interproximal clinical attachment level, number of missing teeth, or dental and medical histories and CAD. The authors conclude that, based on these results, gingival inflammation may be considered a more significant risk factor for CAD than previously reported. 4 tables. 18 references. •

Renal Angioplasty for Lowering Blood Pressure (editorial) Source: New England Journal of Medicine. 342(14): 1042-1043. April 6, 2000. Contact: Available from New England Journal of Medicine. 860 Winter Street, Waltham, MA 02451-1413. (781) 893-3800. Website:www.nejm.org. Summary: This editorial comments on a study published in this same issue of the New England Journal of Medicine and offers a historical perspective on the use of renal angioplasty (the reconstruction of damaged blood vessels) for lowering blood pressure. The research study concluded that renal angioplasty is no more effective for control of blood pressure than antihypertensive drug therapy alone. The editorial authors comment that if this study had been performed two decades ago, when today's potent antihypertensive drugs were not available, the outcome might well have been different. The editorial reviews the strengths and weaknesses of the research. The authors conclude that the screening of all hypertensive patients for atherosclerotic renal artery stenosis (narrowing of the artery that supplies the kidney) in order to treat stenosis with renal angioplasty is no longer justified. However, renal angioplasty may still be advisable in some patients whose blood pressure is not controlled with drug therapy, or in those patients with renal artery stenosis in a single kidney. A separate issue is those patients in whom the need for preservation of renal function may be an indication for renal angioplasty.

Federally Funded Research on Angioplasty The U.S. Government supports a variety of research studies relating to angioplasty. These studies are tracked by the Office of Extramural Research at the National Institutes of

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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 angioplasty. 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 angioplasty. The following is typical of the type of information found when searching the CRISP database for angioplasty: •

Project Title: ADHESION DEVELOPMENT

SIGNALING

IN

VASCULAR

GROWTH

AND

Principal Investigator & Institution: Taylor, Joan M.; Pathology and Lab Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Proliferation and migration of smooth muscle cells (SMC) are critical processes during vasculogenesis and blood vessel maturation and are important in the pathophysiology of several prominent cardiovascular disease states such as atherosclerosis, restenosis following balloon angioplasty, and hypertension. Evidence suggests that the mitogenic responses of SMC during development and disease are modulated by extracellular matrix (ECM) proteins and signaling through the integrin-associated protein tyrosine kinase, focal adhesion kinase (FAK). Interestingly, we have shown that the expression of FRNK (FAK Related Non-Kinase), a dominantinhibitory form of FAK is restricted to SMC with particularly high levels observed in large blood vessels. We hypothesize that in SMC, FRNK regulates growth and development by modifying adhesion-dependent growth factor signaling. As such, FRNK may prove an effective therapeutic target for disregulated SMC growth following endovascular manipulation. We propose to employ biochemical and genetic approaches to characterize the role of FRNK in vascular growth and development. The specific aims of this proposal are as follows: 1) Define the mechanism by which FRNK attenuates growth factor and adhesion-dependent cell proliferation and migration in vascular SMC. We will characterize which SMC mitogens are regulated by FAK/FRNK signaling using DNA synthesis and chemotaxis assays and define the signaling pathways altered by FRNK overexpression. Particular emphasis will be placed on defining the mechanism by which FRNK attenuates growth factor signaling in SMC. 2) Study the in vivo regulation of FRNK expression during development. We will employ tissue-specific in situ approaches to characterize FRNK expression patterns in the developing mouse. 3) Evaluate a functional role for FAK/FRNK signaling in vascular growth and development. We will employ a transgenic gene targeting approach to determine the effect of SM-specific overexpression of FRNK on vascular development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

•

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Project Title: ALPHA ADRENOCEPTORS IN VASCULAR WALL GROWTH Principal Investigator & Institution: Faber, James E.; Professor; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAY-2003 Summary: This proposal will determine if local sympathetic activation of alpha1adrenergic receptors (AR) worsens the neointimal and adventitial growth responses to balloon angioplasty, as a model of vascular wall fibroproliferative disease. Evidence suggests that angioplasty augments local adrenergic neurotransmission. Furthermore, alpha1AR activation induces growth of smooth muscle cells (SMC) and adventitial fibroblasts (AFB). Although alpha1AR stimulation has been proposed to contribute to hypertensive wall hypertrophy and fibrosis, exacerbate atherosclerosis, and to worsen restenosis after angioplasty and stenting, no studies have directly examined these hypotheses because of absence of local drug delivery systems that prevent confounding systemic hemodynamic and humoral actions. We have devised a novel system that overcomes this problem. This, plus recently developed highly selective alpha1AR subtype antagonists, knockout mice and antisense strategies, will be used to investigate the hypothesis that stimulation of a specific alpha1AR subtype on SMCs and/or adventitial fibroblasts (AFB) may contribute importantly to intimal lesion growth and adventitial fibrosis. A possible key role for AFBs in vascular wall disease is just now emerging. We have developed a unique model system for study of these cells in vivo and in vitro, and have made the intriguing finding that AFBs cells differ from other fibroblasts in the array of cytoskeletal proteins that they express, and in their unexpected expression of multiple alphaAR subtypes. Moreover, AFBs undergo a remarkable phenotypic transformation that may be important in vascular wall disease. Aim 1 will determine if alpha1AR stimulation directly induces growth of the normal vascular wall, and importantly, if it worsens neointimal growth and adventitial fibrosis after injury. Aim 2 will determine how injury alters alphaAR expression in the intima, media and adventitia; and which alpha1-AR subtype(s) on SMCs and AFBs augments normal and injured wall growth. Aim 3 will examine if alpha1AR stimulation worsens neointimal or adventitial growth by augmenting SMC and/or AFB proliferation, migration, or matrix elaboration in vivo. Aim 4 will use cultured SMCs and AFBs to test our hypothesis that alpha1AR stimulation adds to-or synergizes with- a specific peptide growth factor(s) to promote SMC and AFB phenotypic transformation, proliferation, migration and/or matrix accumulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: AN INTRAVASCULAR X-RAY SOURCE FOR RESTENOSIS TREATMENT Principal Investigator & Institution: Shefer, Ruth E.; President; Newton Scientific, Inc. 245 Bent St Cambridge, Ma 02141 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-JAN-2004 Summary: (Applicant's abstract verbatim): The goal of this project is to develop a miniature, catheter-based X-ray source for radiation therapy to prevent restenosis after percutaneous transluminal angioplasty. Restenosis affects 30 percent to 50 percent of angioplasty patients within six months of the procedure. Intravascular radiation therapy has been shown to be effective in preventing or significantly delaying restenosis in both coronary and peripheral vessels. Ongoing clinical trials of intravascular brachytherapy for restenosis use gamma or beta-emitting radioisotopes delivered to the

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angioplasty site via a guide catheter and withdrawn when sufficient dose has been delivered to the arterial segment. These radioactive devices have significant drawbacks, including limited dose rates and fixed dose-depth profiles, safety hazards to patient and medical personnel, and restrictions on transportation, storage and disposal. In Phase I, we evaluated the feasibility of developing a disposable, electrically-powered X-ray source small enough to reach the angioplasty site through a standard guide catheter. Advantages of the proposed source include on-off capability, high radiation dose rate, user-controlled dose-depth profile, and elimination of the regulatory and safety issues that accompany the use of radioactive materials. The Phase I results demonstrate the feasibility of constructing an ultra-miniature X-ray source with the required radiation dose rate and dose-depth characteristics. A fully operational X-ray source and delivery catheter will be developed in Phase II and tested in phantoms. PROPOSED COMMERCIAL APPLICATION: Approximately 1,000,000 coronary angioplasty procedures are performed worldwide each year. If radiation therapy for restenosis is proven effective in clinical trials, this represents a large market for catheter-based radiation devices. A flexible, catheter-based X-ray source also has many potential applications in radiation oncology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANGIOGENIC MECHANISMS

BYPASS

&

GENE

THERAPY

RESPONSE

Principal Investigator & Institution: Rosengart, Todd K.; Evanston Northwestern Healthcare Evanston, Il 60201 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Atherosclerosis remains the leading cause of death in the Western world, despite the refinement of such life-saving techniques as angioplasty and bypass surgery, in part because the application of these therapies remains limited by the diffuse nature of this disease and the development of restenoses in many patients. The growth of new vasculature (neovascularization) is a critical but limited biologic response to ischemia that induces partial reperfusion of ischemic tissues. Therapeutic angiogenesis is a novel revascularization strategy whereby a growth factor polypeptide is administered for the purpose of augmenting the native neovascularization process. Gene therapy may be uniquely suitable for inducing therapeutic angiogenesis, especially in relatively inaccessible sites such as the heart, in that it provides sustained growth factor delivery after only a single dose of an appropriate vector. Despite data that vascular endothelial growth factor (VEGF) delivered via adenovirus (Ad) enhances angiogenesis and preserves tissue perfusion, the mechanisms underlying therapeutic angiogenesis remain poorly understood. Specifically, the role of ischemia and the necessary duration of expression of VEGF and other potential angiogenesis mediators in permitting induction and persistence of neovascularization are unknown. The aims of this proposal are therefore to determine, in established animal models, whether: 1) ischemia is requisite in inducing and allowing the persistence of physiologically relevant neovascularization, 2) neovascularization can be enhanced by angiogenesis "co-factors", such as the angiopoietins, which are thought to play a role in vascular sprouting and stabilization, and 3) transgene expression can be regulated with selected promoters, including cardiac specific and glucocorticoid response elements, to allow the expression of relevant transgenes at specified locations or times ("stealth" gene therapy), respectively. The successful accomplishment of these aims should provide significant insights into the mechanisms underlying therapeutic angiogenesis and thereby enhance our ability to optimally apply clinically this biologic approach to the treatment of atherosclerosis.

Studies

9

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

Project Title: ANTIPROLIFERATIVE HYPERPLASIA

RX

FOR

VENOUS

NEOINTIMAL

Principal Investigator & Institution: Roy-Chaudhury, Prabir; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Hemodialysis vascular access dysfunction is the single most important cause of hospitalization in hemodialysis patients and is responsible for a very significant morbidity within this patient population. Thrombosis of PTFE dialysis grafts due to venous stenosis as a result of venous neointimal hyperplasia (VNH), is the most common cause of vascular access dysfunction. Surprisingly, there are currently no effective therapeutic interventions for VNH despite its clinical importance. Analysis of cell types and cytokines in dialysis patients with venous stenosis due to VNH and data from a validated pig model of venous neointimal hyperplasia, that is very similar to the human lesion have been described. These studies clearly demonstrate that smooth muscle cell (SMC) proliferation and the formation of microvessels (endothelial cell proliferation), within the neointima and adventitia are critical features of VNH. In addition, it is likely that PTFE dialysis grafts are the ideal clinical model to test out novel local interventions, in view of their superficial location and easy accessibility. It is therefore proposed to test out novel locally delivered antiproliferative therapies in a validated pig model of VNH, in the hope of being able to rapidly translate positive findings into a clinical setting of great need. Three local interventions will be evaluated in this proposal for their anti-proliferative effects. (a) External radiation therapy: Initial studies in the pig model, have demonstrated a reduction in VNH (albeit less than in models of coronary angioplasty), with a single dose of l6Gy. We now plan to optimize a radiation schedule for VNH by testing out 3 different radiation regimens (b) Local polymeric delivery of paclitaxel and TNP-470: A local polymeric delivery system comprising ethylene-vinyl-acetate matrices loaded with paclitaxel and TNP-470 (both are potent anti-proliferative agents) will be developed and tested in vitro against SMC and endothelial cells. Polymeric matrices will then be wrapped around the graft vein anastomosis in a perivascular configuration in an attempt to reduce luminal stenosis and VNH. (c) Combination radiation therapy and local anti-proliferative therapy: The most effective radiation and anti-proliferative regimens from (a) and (b) will be combined in this final analysis, in the hope of achieving a synergistic effect. We believe that the results from this study could transform the clinical care of hemodialysis patients and at the same time result in the successful clinical application of local therapy for the treatment of neointimal hyperplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APOLIPOPROTEIN E--IMPACT ON VASCULAR CELL FUNCTIONS Principal Investigator & Institution: Hui, David Y.; Professor and Vice Chairman for Research; Pathology and Lab Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: The importance of apolipoprotein (apo) E level and function in protection against vascular diseases has clearly been established. However, most of the research on the role of apoE has focused on its role in cholesterol metabolism. In view of

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observations that apoE gene polymorphism also impact on the potential for restenosis after percutaneous transluminal coronary angioplasty, a process in which cholesterol deposition is a late event, we hypothesize that apoE may also confer protection against neointimal formation and arterial hyperplasia by mechanisms independent of its role in cholesterol and lipoprotein transport. The overall goal of this research project is to provide insights into additional mechanisms by which apoE confers protection against vascular disease. Based on strong Preliminary Results obtained in in vitro experiments, we hypothesize that apoE has cytostatic functions in vivo and that apoE attenuates vascular occlusive diseases after arterial injury. We postulate that this protective effect is mediated through signal transduction mechanisms subsequent to apoE interaction with one or more members of the LDL receptor gene family on smooth muscle cells. Specific Aim 1 will use apoE transgenic and knockout mice to test the hypothesis that apoE has cytostatic function in the arterial wall and protects against injury-induced lesion development by inhibiting proliferation and migration of vascular smooth muscle cells. Specific Aim 2 will use both in vitro cell culture experiments and in vivo studies with apoE transgenic mice to examine the effectiveness of various apoE isoforms in protecting against neointimal formation and arterial hyperplasia in response to injury. Specific Aim 3 is designed to explore mechanisms underlying the cytostatic function of apoE. In vitro studies with vascular smooth muscle cells in culture will be used to test the hypothesis that apoE inhibits the Ras signaling cascade that is essential for growth factor-induced migration and proliferation of vascular smooth muscle cells. Specific Aim 4 is designed to identify the receptor on smooth muscle cells that is responsible for mediating the cytostatic function of apoE. Initial attention will focus on the possible involvement of LRP or the VLDL receptor in this process. Transgenic mice overexpressing human apoE will be crossbred with receptor associated proteindefective knockout mice to obtain smooth muscle cells and animals for these experiments. Understanding the relationship between apoE function and vascular cell response to injury will help to identify subjects at risk for arterial diseases, especially those at risk for restenosis after balloon angioplasty. The results will also contribute valuable information for future studies aimed at using apoE as gene therapy for treatment of arterial occlusive diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ARTERIAL IRRADIATION

BIOLOGIC

RESPONSE

TO

ENDOVASCULAR

Principal Investigator & Institution: Robinson, Keith A.; Assistant Professor of Medicine; American Cardiovascular Research Inst 5665 Peachtree Dunwoody Rd, Ste 225 Atlanta, Ga 30342 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAR-2004 Summary: Low-dose (7 to 14 Gy) endovascular irradiation (brachytherapy) has been shown to be effective in animal models, for inhibiting the formation of proliferative neointimal lesions after vascular injury. At higher radiation doses (greater than or equal to 28 Gy) an inhibition of negative remodeling or chronic vessel constriction is also seen. Such findings have prompted several clinical trials of vascular brachytherapy for prevention of restenosis after balloon angioplasty and endovascular stenting; preliminary results available in some studies have documented a reduction in restenosis rate. While the suppression of vascular cell cycling has been suggested as one mechanism for the inhibition of neointima, the effects of radiation on arterial cellular functions and the response to vascular injury are still poorly understood. The purpose of the proposed investigation is to study effects of endovascular ionizing radiation on

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arterial cell, molecular, and physiologic mechanisms regulating: 1) potential changes in functional aspects of arterial biology consequent to ionizing radiation in the presence and absence of angioplasty injury, especially a) vasomotor reactivity and b) thrombogenicity of the luminal surface; and 2) alterations in extracellular matrix content which would influence vessel integrity and architecture. These studies will employ a relevant animal model system, with defined physiologic and pathologic outcomes. With respect to arterial healing events, influences of brachytherapy on thrombosis, reendothelialization, and extracellular matrix composition will be examined. Determinants of vasomotor function will also be assessed, including effects of brachytherapy on superoxide production, endothelium-dependent and -independent relaxation responses, and nitric oxide synthesis. These studies will therefore determine, using an established pig coronary artery model system, the role of endovascular irradiation in modifying key functional and structural components of the coronary arteries in the presence and absence of a balloon catheter- induced arterial injury and healing response analogous to restenosis. The investigations will thus help fill crucial missing gaps in our knowledge about the new technique of endovascular brachytherapy for restenosis prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BARI II - FIBRINOLYSIS AND COAGULATION CORE Principal Investigator & Institution: Sobel, Burton E.; Professor; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-MAY-2007 Summary: The revised Bypass Angioplasty Revascularization Investigation (BARI) II study proposes to evaluate treatments for Type 2 diabetic patients with angiographically proven coronary artery disease and stable angina or ischemia. For this rapidly growing patient population with very poor prognosis and quality of life, revascularization has been less beneficial than in nondiabetics. Using a factorial design, BARI II will compare revascularization combined with aggressive medical anti-ischemia treatment to aggressive medical anti-ischemia treatment alone; simultaneously, BARI II will compare two glycemic control strategies, insulin sensitization versus insulin provision. All patients will have target HbA1c values < 7.5%, and uniform control of hypertension, dyslipidemia and obesity following recommended guidelines. A total of 2,600 patients will be recruited, randomized, treated, and followed at 30 clinical centers. Five-year mortality will be the primary endpoint analyzed by intention-to-treat. The Coordinating Center (CC) will assume responsibility for overall trial operations including clinical site selection, data management using an Internet system, and statistical analysis. Within the CC will be operational units for the management of diabetes control, lipids and hypertension. Detailed data on potential mechanisms of macrovascular events will be collected with centralized evaluations of ECGs, lipids and HbA1c levels. A fibrinolysis core laboratory will explore the effect of glycemic control strategy on the progression and mechanism of vasculopathy, including changes in PAI-1 activity and gene expression. The investigators will evaluate the relative economic costs associated with revascularization approaches and diabetes control (Separate application for the ECG Core, the Fibrinolysis Core and the Economics Core complement this lead application). This 7-year application includes a 6-month protocol finalization phase, 2 years of patient recruitment and an additional 4.5 years of follow-up. BARI II aims to answer critical scientific questions regarding treatment efficacy in Type 2 diabetic patients with stable CAD. The investigators further expect that this collaborative effort will translate into a

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new practical clinical paradigm that will be used for treatment of Type II diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BARI II GRANT PROPOSAL FOR ECG CORE LABORATORY Principal Investigator & Institution: Chaitman, Bernard R.; Professor of Medicine and Director, Card; Internal Medicine; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-MAY-2007 Summary: The revised Bypass Angioplasty Revascularization Investigation (BARI) II study proposes to evaluate treatments for Type 2 diabetic patients with angiographically proven coronary artery disease and stable angina or ischemia. For this rapidly growing patient population with very poor prognosis and quality of life, revascularization has been less beneficial than in nondiabetics. Using a factorial design, BARI II will compare revascularization combined with aggressive medical anti-ischemia treatment to aggressive medical anti-ischemia treatment alone; simultaneously, BARI II will compare two glycemic control strategies, insulin sensitization versus insulin provision. All patients will have target HbA1c values < 7.5%, and uniform control of hypertension, dyslipidemia and obesity following recommended guidelines. A total of 2,600 patients will be recruited, randomized, treated, and followed at 30 clinical centers. Five-year mortality will be the primary endpoint analyzed by intention-to-treat. The Coordinating Center (CC) will assume responsibility for overall trial operations including clinical site selection, data management using an Internet system, and statistical analysis. Within the CC will be operational units for the management of diabetes control, lipids and hypertension. Detailed data on potential mechanisms of macrovascular events will be collected with centralized evaluations of ECGs, lipids and HbA1c levels. A fibrinolysis core laboratory will explore the effect of glycemic control strategy on the progression and mechanism of vasculopathy, including changes in PAI-1 activity and gene expression. The investigators will evaluate the relative economic costs associated with revascularization approaches and diabetes control (Separate application for the ECG Core, the Fibrinolysis Core and the Economics Core complement this lead application). This 7-year application includes a 6-month protocol finalization phase, 2 years of patient recruitment and an additional 4.5 years of follow-up. BARI II aims to answer critical scientific questions regarding treatment efficacy in Type 2 diabetic patients with stable CAD. The investigators further expect that this collaborative effort will translate into a new practical clinical paradigm that will be used for treatment of Type II diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: B-ARRESTINS FUNCTION/GROWTH

AND

GPCR

KINASES

IN

VASCULAR

Principal Investigator & Institution: Lefkowitz, Robert J.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by the applicant): G protein-coupled receptors (GPCRs) including those for catecholamines and angiotensin II regulate vascular reactivity, including vasoconstriction and vasodilation, as well as vascular smooth muscle (VSM) cell mitogenesis and migration. Vascular reactivity may be perturbed in hypertension, whereas altered VSM mitogenesis and migration characterize pathological intimal hyperplasia following surgical bypass or restenosis after arterial angioplasty. Following

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GPCR activation, GPCRs are phosphorylated by one of seven GPCR kinases (GRKs) and then one of two isoforms of b-arrestin is recruited to the receptor. b-arrestin binding sterically interdicts further signaling to G proteins, leading to receptor desensitization and attenuation of signaling. b-arrestins also play positive roles in signaling, serving as adapters and scaffolds to organize GPCR- mediated activation of MAP kinase cascades, such as the extracellular signal regulated kinases (ERK 1/2). These MAP kinases regulate mitogenesis and migration of VSM cells and other cell types. Our group has developed mice in which the GRKs and b-arrestins have been individually knocked out. We will utilize these animals, and VSM cells from them, to test the central hypothesis that regulation of GPCR signaling by b-arrestins and GRKs is critical for normal vascular homeostasis. Our specific aims are 1) To elucidate the vascular phenotype of barrestin and GRK knockout mice by analyzing conscious and anesthetized blood pressure responses and vascular reactivity using isolated aortic rings; 2) To elucidate the roles of b-arrestins and GRKs in signaling via endogenous GPCRs in isolated arterial and venous VSM cells from wild type and knockout mice by determining both A) the specificity of b-arrestins and GRKs in desensitizing second messenger signaling via endogenous GPCRs and B) the roles of b-arrestins and GRKs in GPCR stimulated ERK activation, proliferation, and migration of VSM cells; and 3) To determine if the loss of specific b-arrestins or GRKs alters in vivo proliferative intimal hyperplasia following mouse vein-graft surgery or arterial injury. These experiments have the potential to lead to the development of new strategies for limiting vein graft failure and restenosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BCR KINASE IN PDGF-MED EFFECTS IN VASCULAR SMOOTH MUSCLE Principal Investigator & Institution: Abe, Jun-Ichi; Assistant Professor; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Growth factors such as platelet-derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of growth factors to their receptors activates intrinsic receptor tyrosine kinases, resulting in tyrosine phosphorylation of receptors themselves and cellular substrate proteins. We determined that the development of intimal thickening after deendothelializing balloon catheterization of rat carotid artery was accompanied by transient 2- to 3- fold increases in the extent of tyrosine phosphorylation of platelet-derived growth factor (PDGF) alpha- and beta-receptors. The human Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene which is causative for leukemia. Bcr encodes a protein with serine/threonine kinase activity, CDC24/dbl homology, a GAP domain, an SH2binding region, and a 14-3-3 binding motif. However, the normal physiological function of Bcr remains unknown. Recent studies in our laboratory have identified that Bcr is expressed in cultured vascular smooth muscle cells (VSMC) and neointimal lesions in a balloon injury model. We also determined that Bcr kinase is rapidly activated by PDGF in VSMC and Bcr overexpression enhances ERK1/2 activity in CHO cells expressing PDGF receptor. Therefore, our main hypothesis is that Bcr, activated by PDGF, may increase the VSMC migration and proliferation and thereby contribute to atherosclerosis and restenosis. Thus understanding The regulatory mechanisms by which PDGF activates Bcr should provide valuable insights into pathways which may play a critical role in cardiovascular disease. To prove this hypothesis the following aims are proposed; Aim 1: Characterize the stream signal mechanisms by which PDGF activates

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Angioplasty

Bcr. Aim 2: Characterize the role of Bcr in regulating ERK1/2 in Bcr overexpression cells. Aim 3: Characterize the role of Bcr-Syp association in regulating PDGF betareceptor tyrosine phosphorylation. Aim 4: Define the role of Bcr in regulating neointimal formation in rat carotid balloon-injury model. To determine the relative importance of the Bcr 14-3-3 binding site and SH2 binding site for Bcr kinase activation and for the effect of Bcr overexpression on PDGF signal transduction, we will transfect deletion and site-directed Bcr mutants into CHO cells expressing PDGF b-receptors. To determine potential targets of Bcr in PDGF signal transduction, we will evaluate the effects of Bcr overexpression on the activity of several PDGF signal transduction molecules, including Syp, Grb2, Ras, and Raf-1. To understand the role of Bcr in injured arteries, we will measure the magnitude and time course of Bcr mRNA and protein expression after balloon injury. We will try to establish a causative link between Bcr and neointimal formation by performing carotid injury in the bcr knock-out mouse. We propose that Bcr is a novel downstream component of PDGF receptor signaling in vascular smooth muscle, and may be a candidate gene responsible for the atherosclerosis and restenosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIORAL AND IMMUNOLOGICAL FACTORS IN CORONARY DISEASE Principal Investigator & Institution: Kop, Willem J.; Assistant Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 06-JUL-2001; Project End 31-MAY-2006 Summary: adapted from Investigator's abstract) Recent studies demonstrate that the immune system plays an important role in coronary artery disease (CAD). Research also shows that psychological factors such as major depressive disorder and acute mental stress are involved in the clinical progression of CAD. Depression is associated with higher levels of immune parameters that play a role in CAD (cytokines, markers of low grade inflammation, infectious pathogen burden, and adhesion molecules), and most of these measures also increase in response to acute physical and mental stress. The pathophysiological mechanisms linking depression and mental stress with adverse cardiovascular outcomes may therefore be mediated by immunological factors. The proposed research will examine clinical outcomes in patients who undergo percutaneous coronary revascularization, because a major problem remains the frequent (20 percent-40 percent) occurrence of coronary restenosis and new cardiac events in the 6 months after the intervention. These adverse outcomes have substantial impact on the costs of medical care and patients' quality of life. Since previous research has not examined the role of behaviorally-induced changes in immune parameters in the prediction of CAD progression, the following immunological measures will be examined: cytokines (IL-1B, IL-4, IL-6, IFNy, TNFa), acute phase proteins (CRP, fibrinogen), lymphocyte counts and differential, adhesion molecules (ICAM-1, LFA, Lselectin), and a composite measure of pathogen burden (CNV, H. pylori, C. pneumoniae). Using a longitudinal design, this project will determine the time course of changes in depression and changes in immune parameters. Moreover, the present study will determine the contribution of behavioral and immunological factors in the clinical progression of coronary disease following coronary angioplasty. These data may therefore improve the identification of patients at risk for recurrent cardiac events and restenosis after coronary angioplasty, and provide further understanding of the pathophysiological mechanisms involved in coronary disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIOVASCULAR GENE THERAPY CENTER Principal Investigator & Institution: Glorioso, Joseph C.; Professor and Chairman; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 28-SEP-2000; Project End 31-AUG-2005 Summary: Despite the dramatic advances in prevention, diagnosis, and treatment made during the last half of the 20th century cardiovascular disease remains the number-one cause of morbidity and death in the United States. The success of angioplasty, vascular surgery procedures, and even heart transplantation (all approaches to treat vasoocclusive disease) is limited by intimal hyperplasia. The success of angioplasty, vascular surgery procedures, and even heart transplantation (all approaches to treat vasoocclusive constant infusions of inotropes or with left ventricular assist devices. However, in many instances these treatments only transiently postpone the inevitable death or transplantation. Clearly more effective and sustainable therapies are needed. Gene therapy offers perhaps the greatest opportunity to make the next major advance in preventing or treating cardiovascular disease. While pharmacologic methods typically require frequent closing, a single gene therapy application may be adequate to prevent, attenuate, or reverse even chronic disease. including useful vectors, methods of delivery and the molecular basis of many cardiovascular diseases in humans is the natural progression of ongoing research in cardiovascular gene therapy at the University of Pittsburgh. Two independent research programs, one aimed at developing gene therapy approaches to treat heart failure and the investigators in the Pittsburgh Human Gene Therapy Center (PHGTC). We now propose to further link these established research programs with the extensive resources of the PHGTC and other key resources in the Cores cardiovascular therapy programs from the bench to the bedside. Second, through our proposed preclinical projects, we will acquire the essential data needed to determine if other promising genes, gene targets and vectors projects, we will develop more effective vectors to target cardiovascular tissues. Fourth, through an organized and comprehensive training program, we will prepare clinician scientists for careers in gene therapy for cardiovascular disease. Fifth, through our coordinating data management core, we will provide communication mechanisms and data organization for our consortium centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CELL-SELECTIVE LIPOSOMAL DRUG DELIVERY IN RESTENOSIS Principal Investigator & Institution: Marchant, Roger E.; Professor of Biomedical Engineering; Biomedical Engineering; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: Clinically significant restenosis occurs in greater than 30 percent of patients receiving percutaneous transluminal coronary angioplasty, and remains prevalent despite efforts to inhibit neointima formation through pharmacological intervention and the use of surface-modified intracoronary stents. The overall goal of the proposed research is to bioengineer new liposome drug delivery systems that selectively bind, or target, cell surface molecules expressed at sites of chronic vascular injury and developing restenotic lesions. We propose to investigate surface modifications of liposomes that (i) target encapsulated drugs directly to the site of vascular injury, by exploiting differences in cell surface phenotypes characteristic of activated cells present in the lesion; and (ii) inhibit protein adsorption to the liposome, thereby increasing the

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Angioplasty

circulation half-life. The proposed targeting strategies are based on the central hypothesis that procoagulant and inflammatory phenotypes of stimulated vascular cells comprise unique cell surface receptors that will bind biomimetic constructs of endogenous ligands presented on the liposome surface. By utilizing these ligands to localize long-circulating liposomes to the lesion, local drug concentrations can be increased to therapeutic levels. Specifically, we shall focus on the design and development of targeting ligands to three cell surface molecules expressed in thrombosis and restenosis: (1) high affinity RGD peptides that bind integrin GPIIb-IIIa on activated platelets; (2) Factor VII-derived peptides that bind tissue factor on stimulated endothelial cells and smooth muscle cells, and (3) high affinity sialyl Lewis x and sialyl Lewis a - derived oligosaccharides that bind E- and/or P-selectins on EC and platelets. We shall examine how the ligand structures modulate binding affinity, and determine how these ligands affect binding and uptake of liposomes by target cells in vitro, and in a rat model of balloon-induced vascular injury in vivo. The physical properties of glycolipids designed to increase circulation lifetimes will be studied to determine the role of surface hydration and bilayer stability in altering liposomal clearance rates. The ability of long-circulating, targeted liposomes to affect neointima formation will be studied in vivo using rapamycin and enoxaparin as a model encapsulated therapeutic agents. By addressing targeting affinity and specificity, and prolonged circulation lifetime, an effective drug delivery vehicle for the management and prevention of thrombosis and restenosis can be achieved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINE RECEPTORS IN VASCULAR DISEASE Principal Investigator & Institution: Nelson, Jay A.; Director & Professor; Molecular Microbiology and Immunology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from Investigator's Abstract): The development of vascular diseases such as atherosclerosis, arterial restenosis following angioplasty, and solid organ transplant vascular sclerosis are chronic inflammatory disease processes that involve multiple factors. Infectious agents such as human cytomegalovirus (HCMV), which chronically persists in individuals following primary infection, have been implicated in the acceleration of these vascular diseases although the mechanism has remained elusive. Recently, we have reported that HCMV infection of arterial smooth muscle cells (SMC) results in cellular migration due to the expression of a virally encoded G protein coupled receptor (US28). Expression of US28 in the presence of CC chemokines including RANTES or MCP-1 was sufficient to promote SMC migration by both chemo kinesis and chemotaxis, which was inhibited by protein tyrosine kinase inhibitors. Therefore, the primary focus of this project is to elucidate the mechanism(s) involved in US28 induced SMC migration and develop an animal model to test the contribution of vitally encoded chemokines in this process. We plan to accomplish these goals in the following specific aims. First, we will identify the structural domains of US28 that mediate SMC migration by generating chimeras between the viral GPCR and CCR5, which cannot induce cell movement. We will also identify the protein tyrosine kinases (PTKs), which are stimulated during the US28 signaling process as a marker for SMC activation. Lastly, in this specific aim we will determine whether all chemokines, which bind US28 induce SMC migration and whether some of these ligands can act as antagonists of GPCR activity. In the second specific aim, we will characterize another Viral GPCR (m33), which is encoded within murine cytomegalovirus (MCMV) and

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induces mouse SMC movement. We will utilize an infectious MCMV BAC clone and shuffle mutagenesis system to identify m33 structural domains that are key to SMC migration. In addition we will identify the PTKs stimulated during m33 stimulation. In the last specific aim, we will examine the contribution of m33 induced SMC migration in the generation of atherosclerosis in ApoE and ApoE/CCR2 knockout mice. The wild type and mutant MCMV BAC clones derived above will be used to infect mice in this part of the project. These experiments will determine the role of m33 in the development of vascular disease and the structural domains of m33, which mediate this process. Completion of these experiments will provide a molecular basis for the role of HCMV in the acceleration of vascular disease as well as provide an animal model to test future intervention therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL TRIALS OF LOCAL PERCUTANEOUS DELIVERY OF BFGF IN CAD Principal Investigator & Institution: Laham, Roger J.; Associate Professor of Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Ischemic coronary disease is the leading cause of morbidity and mortality in the Western world. Most available therapeutic approaches aim either at relieving symptoms by reducing myocardial oxygen demand, preventing further disease progression by modifying risk factors, restoring flow to a localized segment of the arterial tree (PTCA or CABG). Therapeutic angiogenesis may restore flow to the ischemic myocardium by creating new venues for blood flow. The purpose of the present investigation will be to examine the therapeutic potential of basic fibroblast growth factor (bFGF) in human ischemic heart disease using percutaneous intrapericardial delivery, define optimal outcome measures for clinical angiogenesis studies using a novel magnetic resonance imaging technique and Biosense electromechanical mapping, and explore novel growth factor deliver methods in animal models of myocardial ischemia, including intramyocardial delivery and gene therapy. We will conduct a clinical trial of therapeutic angiogenesis in patients with ischemic heart disease who are suboptimal candidates for standard revascularization strategies. This trial will examine the angiogenic efficacy of bFGF administered using a novel percutaneous subxyphoid intrapericardial delivery technique. We will investigate the effects of bFGF treatment on clinical parameters, left ventricular function, coronary angiography, and on the size and extent of myocardial ischemia using stress nuclear perfusion scans. Biosense NOGA outcome variables in several ongoing clinical angiogenesis studies and laser myocardial revascularization studies comparing these two treatment strategies. In particular, we will validate two novel outcome measures: magnetic resonance imaging and Biosense NOGA mapping. Finally, we will develop novel delivery strategies in a porcine model of chronic myocardial ischemia and mouse matrigel and infarction models including intramyocardial delivery and gene therapy, and compare protein and gene therapy strategies for growth factor-induced angiogenesis. These novel delivery strategy, if successful, will be investigated clinically. These interrelated projects constitute a cohesive research program aimed at elucidating various aspects of therapeutic angiogenesis. Even though the problem, we wish to address, the techniques involved are necessarily broad, ranging from clinical trials, investigation of novel delivery strategies in animal models, and development of a standardized platforms for the conduction of future trials. This should lead to a novel

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Angioplasty

approach to the treatment of ischemic heart disease and a better understanding of the mechanisms of growth- factor and laser induced "angiogenesis". Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE CLINICAL TRIALS IN VASCULAR ACCESS Principal Investigator & Institution: Dixon, Bradley S.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: The Eastern Iowa Western Illinois Vascular Access Consortium (EIWIVAC) is a consortium of hemodialysis units surrounding the University of Iowa co-founded by a vascular biologist and an expert in clinical trials design to address the problem of vascular access failure. Hemodialysis vascular access failure is a frequent cause of morbidity and a major expense in caring for hemodialysis patients. The cause of access failure is neointimal hyperplasia leading to stenosis and thrombosis. This process occurs in both arteriovenous grafts (AVG) and native fistulas (AVF). The hypothesis underlying the present proposal is that pharmacological agents that inhibit vascular smooth muscle cell (vsmc) proliferation will decrease the neointimal hyperplasia and prolong vascular access survival. Both HMG CoA reductase inhibitors and dipyridamole have been shown to inhibit vascular smooth muscle cell proliferation. HMG CoA reductase inhibitors prevent the isoprenylation of small GTP binding proteins such as Ras that are needed for cell proliferation. Dipyridamole increases extracellular adenosine levels that can inhibit proliferation by unclear mechanisms. Studies from our lab have shown that combined treatment with these agents in low doses is additive or even synergistic at inhibiting vsmc proliferation. Therefore, we propose a randomized placebo controlled primary prevention trial using a factorial design to test whether treatment with either dipyridamole or an HMG CoA reductase inhibitor will increase primary survival of a newly created vascular access: either an AVG or an AVF. In addition, we briefly propose two additional trials. With access monitoring to detect stenosis before access failure, many prevalent accesses will require angioplasty. However, the restenosis rate after angioplasty is very high and resistant to many pharmacological agents. We propose in a second trial to test the hypothesis that the more potent antiproliferative effects of rapamycin in combination with an HMG CoA reductase inhibitor will inhibit the smooth muscle cell proliferation leading to restenosis. Finally, data shows that an upper arm native fistula (UAF) has superior survival to an AVG. However, the UAF appears to be underutilized in part because of concerns over high access flow rates and the possibility of increased heart failure and distal steal syndromes. While a randomized trial is not possible, we propose to establish a registry to examine the safety of a UAF compared to an AVG. If safety issues can be addressed, increased utilization of UAF may be the most cost-effective intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONTROL PROLIFERATION

OF

VASCULAR

SMOOTH

MUSCLE

CELL

Principal Investigator & Institution: Nugent, Matthew A.; Professor; Biochemistry; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-DEC-2004 Summary: Cardiovascular disease is the number one cause of death in the United States. The migration and growth of vascular smooth muscle cells within the arterial intima is a hallmark of atherosclerosis and is a major limiting factor in angioplasty, vascular bypass

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surgery and organ transplantation. Although heparin and heparan sulfate proteoglycans (HSPG) have been identified as potent inhibitors of vascular smooth muscle cell growth, these same molecules have also been shown to enhance the proliferative activity of heparin-binding growth factors such as basic fibroblast growth factor (FGF2). The mechanisms of vascular cell growth regulation by HSPG are complex and remain poorly defined. The dual function of HSPG as growth factor stimulators and inhibitors appears to relate to the specific HSPG structure and localization within cells and the extracellular matrix. Consequently, the overall goals of this proposal are 1) to determine how HSPGs control the activity of heparin-binding growth factors in vascular smooth muscle cells, and 2) to identify the factors that dictate the function of endothelial-derived HSPG, perlecan. We will conduct parallel studies on, 1) the regulation of intracellular trafficking and activity of FGF2 and heparin-binding EGF-like growth factor (HB-EGF) by HSPG in smooth muscle cells (SMC), and 2) the physical and chemical characteristics of endothelial cell perlecan that dictate its ability to regulate heparin-binding growth factor activity. The specific aims of this proposal are to identify mechanisms of intracellular processing of FGF2 and HB-EGF in SMC, define the relationship between HSPG and FGF2 activity in SMC, and establish the structure/function relationships for endothelial derived-perlecan. Our studies will provide critical information on the intracellular function of growth factors and HSPG and will potentially identify conditions where the homeostatic balance between vascular repair and disease can be manipulated by targeting the HSPGs involved. These studies will provide important insight into the rational design of new therapies aimed at intervening in the vascular disease process to facilitate repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFARCTION

CORONARY

MICROCIRCULATION-ACUTE

MYOCARDIAL

Principal Investigator & Institution: Kaul, Sanjiv; Professor of Cardiology; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-MAY-2005 Summary: (The applicant's description verbatim): Despite improved management strategies for AMI, proper selection of patients for these strategies is still in its infancy. One of the main reasons is the use of insensitive markers of acute coronary occlusion, reperfusion, and infarction in the clinical setting. Routine use of the EKG and cardiac enzymes in patients with AMI, although inexpensive and easy to perform, has limited our ability to select individual patients for customized treatment. For instance, we still use EKG to diagnose AMI despite the fact that only one-third to two-fifth of all AMI patients have a diagnostic EKG at the time of hospital presentation. We use cardiac enzymes for the confirmation of AMI, but these become positive several hours after coronary occlusion, and are of little value in determining immediate management strategies for patients with AMI. The infarct size can be no larger than the risk area (the region with hypoperfusion after a coronary artery is occluded). If the risk area is small, thrombolysis may not be worth the risk and angioplasty may not be worth the cost. If there is adequate collateral MBF within the risk area that will maintain myocardial viability, immediate intervention may not even be necessary. On the other hand, if thrombolysis fails to achieve tissue reperfusion, rescue angioplasty with or without a drug that limits microvascular injury may be indicated. Finally, the transmural extent of infarction may determine which patient will most benefit from an ACE inhibitor. At present, we do not stratify patients in a manner to optimize their treatment. We hypothesize that by imaging the myocardial microvasculature in patients with

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suspected AMI we can: 1) detect AMI and determine the ultimate infarct size despite persistent coronary occlusion. 2) Determine the success of tissue reperfusion and the effect of intravenous administration of adenosine on coronary microvascular perfusion and infarct size. 3) Determine the effect of the extent of microvascular abnormalities after AMI on LV remodeling and the effect of an ACE inhibitor that causes angiogenesis on this remodeling; and 4) Determine the long-term prognostic value of normal and abnormal microvascular perfusion patterns after the initial management of AMI. We will study the myocardial microvascular using myocardial contrast echocardiography, a newly developed technique that can provide a noninvasive assessment of the myocardial microvasculature in humans. The study aims will be to test the 4 abovementioned hypotheses in patients with suspected AMI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COUPLES INTERVENTION FOR CARDIAC RISK REDUCTION Principal Investigator & Institution: Sher, Tamara G.; Psychology; Illinois Institute of Technology Main Building, Room 301 Chicago, Il 606163793 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: Long-term maintenance of behavioral change to reduce health risk factors is essential to producing a positive effect on medical outcomes. The proposed study will determine whether an on going, long-term relationship can help patients with recent cardiac events or symptoms adhere to three risk-reduction behavioral interventions and to maintain healthy behavioral changes. The couples intervention is designed to (a) change the patient's physical and social environment to facilitate cardiac risk- reducing behavioral changes, (b) optimize social reinforcement and motivation for behavior change between the partners, and (c) decrease relationship stress related to patient's illness and other factors. The state-of-the-risk-reducing behavioral interventions will target three areas of change for cardiac patients in which long-term adherence is problematic: exercise, weight management, and adherence to lipid-lowering medication. Participants will be randomized to standard behavioral treatment or standard treatment plus the couples intervention. Following a pilot study to refine the couples intervention, 160 patients will be enrolled form Rush-Presbyterian-St.Luke's Medical Center and Cook County Hospital in Chicago. To enhance the salience of their health risks, participants will have had a cardiovascular event or acute symptoms (e.g., MI or angina) or a riskreducing medical or surgical procedure (e.g., CABG or angioplasty). Participants will be referred to the study when their physician or medical caregiver determines that they require all three behavioral interventions to reduce their health risks (estimated as 50 percent of all patients eligible for cardiac rehabilitation). They must also have a partner (spouse or live- in-partner) who is willing to participate in the program should the participant be assigned to the couples component. Referral sources have been developed to obtain patients from diverse economic and social backgrounds. Patients will be followed in the study for 18 months. Behavioral outcomes to be assessed include adherence cardiac rehabilitation exercise regimen; exercise capacity; achievement of weight loss goals, maintenance of weight loss, and adherence to recommended dietary recommendations; and changes to lipid values and adherence to lipid-lowering medication. Psychosocial outcomes to be assessed include patient mood, illness coping, and quality of life. Health outcomes will also be monitored, including occurrence of acute events, hospitalizations, and changes in symptom patterns and medications. The study is intended to determine whether a short-term intervention to alter a long-term relationship can result in sustained behavioral change, improved quality of life, and ongoing health benefits for heart patients.

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

Project Title: CYTOMEGALOVIRUS INFECTION OF BLOOD VESSELS Principal Investigator & Institution: Liu, Fenyong; Associate Professor; Infectious Diseases; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Human cytomegalovirus (HCMV) causes one of the most common opportunistic infections in immunocompromised individuals, including organ transplant recipients and AIDS patients. Moreover, HCMV has also been implicated as a possible etiologic factor in the pathogenesis of vascular diseases, including atherosclerosis, arterial restenosis following angioplasty, and solid organ transplant vascular sclerosis. CMV infection in the aorta plays a key role in the development of viral-associated vascular diseases. The great vessels can be the sites for both acute and latent viral infections. Ongoing infections in the vessels facilitate the development of vascular diseases by (a) generating local lesions and injury of the endothelium, (b) up-regulating the expression of cell adhesion molecules and chemokines that induce inflammatory response, and (c) enhancing proliferation and migration of smooth muscle cells. Protection of patients, especially those who are immunocompromised, from developing CMV-associated vascular diseases requires eliminating HCMV infection from the blood vessels and blocking viral replication in these tissues. Understanding the mechanism of CMV infections in the vessels will provide insight into treatment and prevention of CMV-associated vascular diseases. Using murine CMV (MCMV) as a model system, the proposed study is to identify the viral genes required for CMV replication in the aorta and to study the functions of these viral determinants in supporting CMV infections in the vascular wall. We have recently generated a pool of MCMV mutants that contain a transposon sequence. We have also isolated a viral mutant that is attenuated in replication in the aorta and is defective in inducing viral-associated vascular diseases including acute arteritis and atherosclerosis. In the proposed research, mice will be infected with viral mutants and those mutants that are defective in replicating in the aorta will be isolated. The pathogenecity of these mutants will be studied, and the genes that are mutated will be identified. Moreover, the mechanism of how the identified viral determinants function in supporting MCMV infections in the aorta and promoting vascular diseases will be investigated. These studies will lead to the identification of viral determinants for infection in the aorta and the investigation of the functions of these genes in the development of CMV-associated vascular diseases. Understanding the mechanism of CMV infection in blood vessels will facilitate the development of novel strategies for treatment and prevention of CMVassociated vascular diseases as well as viral systemic infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS OF PROCEDURE USE IN MYOCARDIAL INFARCTION Principal Investigator & Institution: Jollis, James G.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: A six-fold variation in the use of cardiac procedures by U.S. geographic region suggests that medical decisions are neither approached in a standard fashion, nor informed by medical evidence. The decision between a patient and their physician is key to efforts aimed at understanding this variation, and at translating medical evidence into

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clinical practice. In considering the factors that lead to treatment decisions, both patient and physician must be examined together. Lacking knowledge and experience, patients presented with treatment decisions must rely on their physicians to act as their advocate. How physicians frame information will strongly influence the patient's decision process. The objective of this research will be to examine the patient and physician factors involved in the selection of diagnostic and therapeutic procedures in the management of coronary artery disease, and to compare procedural strategies related to patient and physician influences to strategies suggested by clinical trials. The study will encompass two main approaches. The first approach will be to directly examine the patient decision process by administering the Shared Decision Program (SDP) to patients facing treatment decisions following cardiac catheterization. The SDP is a computer based interactive video device that provides patients with easily understood information about their disease and potential therapeutic options in a neutrally framed format. The program also provides viewers with individualized comparisons of survival according for angioplasty, bypass surgery, and medical therapy. If patients are given sufficient information about their disease process and treatment options, they have a greater potential to actively participate in decisions about procedures, possibly selecting those therapies most consistent with medical evidence. The second approach will involve an examination of the physician factors related to differences in cardiac procedure use following acute myocardial infarction. For this approach, we will take advantage of the data available at Duke to develop a longitudinal description of myocardial infarction care from hospital admission through long term follow up, including detailed patient descriptors, inpatient and outpatient cardiac procedures, daily records of physician care, rehospitalizations, and survival status. Using this information, we will examine procedural variation according to the characteristics of the admitting physician. We will also examine "which rate is right?" by comparing adjusted outcomes (mortality, resource use, and costs), and by comparing procedure use to approaches based on medical evidence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIGITAL OPTICAL IMAGING OF VASCULAR GENE THERAPY Principal Investigator & Institution: Yang, Xiaoming; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract): Atherosclerotic cardiovascular disease is the leading cause of mortality in the United States. Gene therapy is a rapidly expanding field with great potential for the treatment of atherosclerotic cardiovascular disease. Several specific genes, such as vascular endothelial growth factor (phVEGF'65), have been shown to be useful for preventing acute thrombosis, blocking postangioplasty restenosis, and stimulating growth of new blood vessels. However, currently, there is no in vivo method for precise monitoring of gene expression within targeted atherosclerotic plaques. The recent discovery of green fluorescent protein (GFP), a marker gene, makes possible the use of intact living cells and organisms as experimental systems. GFP has been widely used as a sensitive reporter and the fluorescence signal emitted from GFP can be detected by optical imaging. This proposal will investigate the use of an innovative digital optical camera, developed at the Center for Medical Optical Imaging at Johns Hopkins University, to detect light signals emitted from GFP. We will test the hypothesis that digital optical imaging can be used to monitor vascular gene therapy, and in vitro fluorescent microscopic imaging of vascular GFPs may be extended to in vivo digital optical imaging of vascular GFPs. To test this

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hypothesis, we will develop a novel VEGF-GFP-lentiviral construct that expresses simultaneously both VEGF (to treat restenosis) and GFP (to track VEGF expression) after vascular gene transfection. In addition, we will develop two novel, extemal and intravascular digital optical imagers as in vivo molecular imaging tools to monitor vascular gene therapy, and validate the results in animal models of atherosclerosis. Since current knowledge about the biodistribution and/or in vivo pharmacokinetics of gene therapy is incomplete and relies primarily on staining of biopsied or post-mortem tissues, this innovative imaging technique will provide a unique opportunity to monitor and control vascular gene therapy in vivo and thus improve the management of atherosclerotic cardiovascular disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOSIMETRY OF BRACHYTHERAPY SOURCES IN MILLIMETER RANGE Principal Investigator & Institution: Nath, Ravinder; Professor; Therapeutic Radiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 31-JUL-2004 Summary: (provided by applicant): Recently, radiotherapy has been shown to be an effective treatment for the prevention of restenosis following angioplasty. In catheterbased systems for intravascular brachytherapy (IVB) a radioactive source is placed in the lumen at a short distance from the target, typically 1 to 3 mm. Both gamma and beta emitters are currently in use for IVB. All sources produce dose distributions with a steep dose gradient in the target volume with dimensions of a few millimeters. However, high energy photon emitters (e.g. (192)Ir), low energy photon emitters (e.g. (103)Pd) or beta emitters (e.g. ((90)Sr/(90)Y) have very different dosimetric and physical characteristics in terms of depth dose penetration, attenuation effects and shielding requirements. IVB delivery devices based on (192)Ir and (90Sr/90Y) have become commercially available and one based on (103)Pd is under development. There is now a critical need to obtain dosimetry parameters for these systems for the determination of dose distributions in the target and surrounding volumes. There is a need to modify the dose calculation formalism of the AAPM Task Group No. 43, which is suited to point-like interstitial brachytherapy sources. We propose a calculation formalism based on cylindrical coordinates, which is better suited to the geometry of catheter-based P/B sources. Also, there is a critical need to validate the manufacturers' dosimetry data by independent investigations using both dosimetry measurements and calculations. We propose to use two independent dosimetry methods (radiochromic film and thermoluminescent [TL} sheet dosimetry) and Monte Carlo calculations (ITS, MCNP and EGS4 codes) to intercompare various results and obtain an accurate set of dosimetry parameters for IVB systems. Our hypothesis is that successful implementation of the various IYB systems requires a better understanding of dosimetry issues at millimeter distances. The principal objective is to determine the dosimetry parameters in the immediate vicinity (within mm) of the various radionuclides (both photon emitters and beta emitters) and to examine critically the dosimetry issues of importance in the clinical implementation of IVB for prevention of restenosis following angioplasty. The goals of the project are to develop tools for the optimization of dose distributions produced within a target volume and uniformity of dose along and around a blood vessel. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: E2F-MEDIATED CONTROL OF VASCULAR GROWTH AND REMODELING Principal Investigator & Institution: Sullenger, Bruce A.; Professor & Vice Chair; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Vascular smooth muscle cell (VSMC) proliferation and migration following by-pass grafting and arterial angioplasty can lead to graft failure and restenosis. This pathological process is known as intimal hyperplasia. Limiting intimal hyperplasia in grafted vessels or a vessel following angioplasty is a critically important therapeutic target. A number of recent studies have attempted to limit VSMC proliferation and intimal hyperplasia by delivering inhibitors of cell cycle proteins to by-pass grafts or sites of angioplasty. One of the most promising approaches, developed by Dzau and colleagues, targets the E2F family of transcription factors for inhibition. A number of studies have shown that the growth suppression action of the retinoblastoma tumor suppressor protein (Rb) and other Rb family members is dependent on their ability to regulate the E2F family of transcription factors. It has also become increasingly clear that the E2F family of transcription factors can be divided into 2 subclasses based upon sequence homology and functional properties. The first subclass, containing E2F1, E2F2 and E2F3, are transcriptional activators that induce quiescent cells to proliferate. The second subclass, E2F4, E2F5 and E2F6 are important in the repression of E2F responsive genes and cell proliferation. Consistent with the repressor role of E2F4, we have recently determined that mice lacking E2F4 undergo accelerated intimal hyperplasia following arterial injury. Our Overall Hypothesis is that inhibition of individual (or subsets of the) E2Fs can reduce or enhance intimal hyperplasia following vessel damage or grafting and that a detailed understanding of how the various E2Fs control vascular smooth muscle cell proliferation during intimal hyperplasia will facilitate the development of more specific and potent inhibitors of this pathological process. Our Specific Aims are 1.) To determine the E2F family members that promote intimal hyperplasia and those that repress this pathological process using genetically modified mice, 2) To explore how perturbations in multiple E2F activities affect intimal hyperplasia and restenosis using genetically modified mice and 3) To develop aptamers that specifically target those E2F family that promote intimal hyperplasia and to evaluate the ability of these aptamers to limit intimal hyperplasia in animal models of vein graft failure and arterial restenosis Thus these experiments will delineate the E2F family member(s) that should be targeted for inhibition to reduce the occurrence of restenosis and vein-graft failure in humans and yield novel therapeutic compounds that may be useful in the treatment of individuals undergoing by-pass surgery or angioplasty. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EARLY DIAGNOSIS AND TREATMENT OF DIALYSIS GRAFT STENOSIS Principal Investigator & Institution: Robbin, Michelle L.; Radiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The broad long-term objective of this proposal is to improve vascular access longevity in chronic renal failure patients on hemodialysis using ultrasound evaluation. Synthetic graft failure after the first month is primarily due to clotting (thrombosis). After the graft thromboses, an underlying graft or draining vein stenosis is found in

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greater than 85 percent of patients, despite aggressive clinical monitoring for stenosis. Patent grafts with stenoses treated with percutaneous transluminal angioplasty (PTA) or surgical revision techniques have longer patency than thrombosed grafts after thrombectomy. Therefore, early stenosis detection with treatment of the hemodynamically significant stenoses found (in patent grafts) should increase graft longevity, thereby decreasing the substantial costs associated with graft failure. We propose to actively test two graft surveillance strategies. This study will test the hypothesis that triannual ultrasound monitoring and percutaneous treatment of detected stenoses will improve hemodialysis graft longevity compared to aggressive clinical monitoring. Specific Aims: To test the hypothesis that: 1). Triannual color flow ultrasound (US) surveillance of hemodialysis grafts can diagnose stenoses that are not detected during aggressive clinical monitoring. 2). PTA of hemodynamically significant stenoses detected by ultrasound surveillance will approximately double graft longevity, from the current 16 months. 3). To determine the ultrasound and angiographic measurement parameters that most accurately predict the longevity of the PTA result. 4). To assess the cost-effectiveness of early color flow US graft stenoses detection and intervention versus aggressive clinical monitoring. Health Relatedness: If color flow US monitoring in addition to aggressive clinical monitoring increases graft longevity and is cost effective as compared to aggressive clinical monitoring alone, this would have important implications for patient management. Increased graft longevity should lead to improved patient quality of life, secondary to a decreased need for thrombectomies, temporary access catheters and surgical placement of new grafts. Research Design and Methods: A randomized, prospective clinical trial will compare triannual color flow US graft monitoring in addition to aggressive clinical monitoring, to aggressive clinical monitoring alone. PTA or surgical revision of hemodynamically significant stenoses detected will be performed. Access patency will be followed for at least 2 years, or until placement of a new access. All other aspects of the patients' medical and dialysis care will follow usual medical standards. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ECONOMIC OUTCOMES OF TREATMENT STRATEGIES IN BAR1-2 Principal Investigator & Institution: Hlatky, Mark A.; Professor of Health Research and Policy; Health Research and Policy; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-MAY-2007 Summary: The revised Bypass Angioplasty Revascularization Investigation (BARI) II study proposes to evaluate treatments for Type 2 diabetic patients with angiographically proven coronary artery disease and stable angina or ischemia. For this rapidly growing patient population with very poor prognosis and quality of life, revascularization has been less beneficial than in nondiabetics. Using a factorial design, BARI II will compare revascularization combined with aggressive medical anti-ischemia treatment to aggressive medical anti-ischemia treatment alone; simultaneously, BARI II will compare two glycemic control strategies, insulin sensitization versus insulin provision. All patients will have target HbA1c values < 7.5%, and uniform control of hypertension, dyslipidemia and obesity following recommended guidelines. A total of 2,600 patients will be recruited, randomized, treated, and followed at 30 clinical centers. Five-year mortality will be the primary endpoint analyzed by intention-to-treat. The Coordinating Center (CC) will assume responsibility for overall trial operations including clinical site selection, data management using an Internet system, and statistical analysis. Within the CC will be operational units for the management of diabetes control, lipids and hypertension. Detailed data on potential mechanisms of macrovascular events will be

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collected with centralized evaluations of ECGs, lipids and HbA1c levels. A fibrinolysis core laboratory will explore the effect of glycemic control strategy on the progression and mechanism of vasculopathy, including changes in PAI-1 activity and gene expression. The investigators will evaluate the relative economic costs associated with revascularization approaches and diabetes control (Separate application for the ECG Core, the Fibrinolysis Core and the Economics Core complement this lead application). This 7-year application includes a 6-month protocol finalization phase, 2 years of patient recruitment and an additional 4.5 years of follow-up. BARI II aims to answer critical scientific questions regarding treatment efficacy in Type 2 diabetic patients with stable CAD. The investigators further expect that this collaborative effort will translate into a new practical clinical paradigm that will be used for treatment of Type II diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF LIPID MODIFICATION ON PAD Principal Investigator & Institution: Lumsden, Alan B.; Associate Proffesor; Surgery; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The benefit of aggressive lipid modification on the prevention of progression of atherosclerosis and restenosis in the lower extremity is unknown. This field is severely hampered by the lack of quantitative measurement of vascular lesion pathology. Complete natural history of restenosis following surgical intervention is not clear. We will combine our expertise and resources at Baylor College of Medicine in a multidisciplinary approach to address these important questions. We hypothesize that an aggressive regimen of serum lipid modification will inhibit the progression of atherosclerosis in femoral arteries and reduce the incidence of restenosis of femoral arteries following endovascular stenting by decreasing thrombosis and inflammation. We will recruit a total of 120 patients with symptomatic femoral artery occlusive disease in one leg. These patients will be treated with endovascular stenting, and randomized into two groups: 1) standard medical care and 2) aggressive lipid modification therapy which increases HDL (>40mg/dl) and decreases LDL (<80 mg/dl) and TG (cl50 mg/dl). We will follow these patients for 2 years. Our Specific Aims are to: 1) Determine the effect of aggressive lipid modification on progression of atherosclerosis and restenosis of femoral arteries. Recently, we have adapted high resolution magnetic resonance imaging (MRI) to study extremity vascular pathology including lesion size, composition, and morphology. This technology will be used to examine both the stented femoral artery for in-stent restenosis and the contralateral femoral artery for atherosclerosis progression or regression. 2) Determine the effects of an aggressive regimen of serum lipid modification on the clinically applicable hemodynamic measurements following femoral artery angioplasty and/or stenting and on the reduction of systemic major cardiovascular events. Large clinical volume and excellent endovascular therapy expertise at Baylor will enable us to evaluate the clinical outcomes, including ankle brachial index (ABI), walking distance, absolute claudication, and duplex ultrasound in a population with significant PAD. 3). Investigate effects of aggressive triple-drug therapy on lipoproteins, inflammation, and relationship to PAD progression, restenosis, and clinical events. Assays of LDL, HDL, TG, Lp(a), particle size and number, hsCRP, TNFalpha, IL-8, MCP-1, sP-selectin, s-ICAM-1, s-VCAM-1, and sCD40L will permit mechanistic insights into PAD progression and clinical events. 4). Investigate the effects of aggressive triple-drug therapy on thrombosis, and relationship to PAD progression, restenosis and clinical events. Association of these studies with

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clinical outcomes and quantitative femoral MR images will permit mechanistic insights into PAD progression and clinical events. This study will provide a novel strategy to retarding or preventing progression of atherosclerosis and restenosis following arterial revascularization procedures. Importantly, our MRI studies will, for the first time, provide quantitative data on the vascular lesions. Finally, these studies will advance our understanding of the molecular mechanisms of inflammation and thrombosis associated with aggressive lipid modification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTROPHYSIOLOGIC EFFECTS OF LATE PCI (OAT-EP) Principal Investigator & Institution: Rashba, Eric J.; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): There is now unequivocal evidence that early coronary reperfusion using either thrombolytics or primary angioplasty results in a long-term mortality reduction among patients who present with acute myocardial infarction (AMI). The mechanism of the benefit of early reperfusion (< 6 hours after AMI onset) was initially attributed to myocardial salvage and the resultant preservation of left ventricular function. However, it is now evident that the survival benefit associated with thrombolytic therapy is not consistently associated with a major improvement in left ventricular ejection fraction (LVEF). These observations led to the formulation of the "late open artery hypothesis", which posits that clinical outcomes can potentially be improved by late reperfusion after AMI. Observational clinical studies have suggested that late patency of the infarct-related artery (IRA) after thrombolysis is associated with a survival benefit that is independent of LVEF and therefore cannot be solely explained by salvage of myocardium. Definitive proof of the late open artery hypothesis is currently lacking, however, because previous prospective studies that have evaluated late percutaneous transluminal coronary angioplasty (PTCA) of occluded IRAs after AMI have produced conflicting results. These considerations led to the organization of the Occluded Artery Trial (OAT), an international, NHLBI-funded randomized trial of 3,200 patients that is testing the hypothesis that mechanical reperfusion of an occluded IRA with PTCA and stenting (PCI) 3-28 days after AMI in high risk patients will reduce a composite endpoint of mortality, recurrent MI, and hospitalization for class IV congestive heart failure. Enhancement of electrical stability is one of the major mechanisms that have been proposed to explain the association of an open IRA with an improved prognosis independent of myocardial salvage. The present OAT-EP ancillary study application will characterize the effects of late PCI of occluded IRAs on the most prognostically important and clinically relevant noninvasive markers of vulnerability to malignant ventricular arrhythmias: heart rate variability, T wave variability, and signalaveraged electrocardiography. These analyses will be performed in 300 patients at baseline, 30 days and one year following MI in order to delineate the effects of late PCI on the autonomic nervous system, ventricular repolarization, and ventricular conduction abnormalities, respectively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FLOW MEASUREMENT AT DIALYSIS ACCESS SALVAGE Principal Investigator & Institution: Krivitski, Nikolai M.; Staff Scientist; Transonic Systems, Inc. 34 Dutch Mill Rd Ithaca, Ny 14850 Timing: Fiscal Year 2002; Project Start 01-NOV-1998; Project End 31-AUG-2004

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Summary: (provided by applicant): Over 100,000 PTFE graft angioplasties are performed in America each year to restore adequate access flow, but up to 50% of the procedures must be repeated within three months. Radiologist now derive interventional efficacy from pressure and vessel diameter measurements. Direct measurement of volume flow (ml/min) would give immediate feedback on procedural success. Transonic Systems proposes to resolve this need by further developing and commercializing an inexpensive catheter-based AngioFlowmeter for measuring blood flow during angioplasty of PTFE grafts and native fistulae. Our Phase-I clinical studies demonstrated that access flow may be measured accurately and repeatably using thermodilution catheters introduced through the angioplasty antegrade sheath and room temperature saline injections. Our Phase-ll plans are to: Attain FDA clearance. Refine and validate the catheter designs and measurement algorithms for catheter placement through antegrade and retrograde introducer sheaths; Refine and validate algorithms to identify whether the flow-limiting stenosis is on the graft arterial or venous side; Demonstrate the system's efficacy in controlled clinical trials; Publish results of the study in preparation for market introduction. At the end of Phase II, Transonic Systems aims to market the AngioFlowmeter as a new quality assurance tool for interventional radiology procedures. PROPOSED COMMERCIAL APPLICATION: An access flow measurement catheter would have routine use during radiological and surgical interventions to restore flow. It would allow quantitative assessment of the efficacy of percutaneous angioplasty and thus support improved outcomes. This may in turn reduce the need for repeat interventions, improve the quality of life for ESRD patients, and reduce healthcare costs in the US by $18 million/year. We aim to market this device to surgical and interventional radiology and interventional radiology suites worldwide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE DELIVERY STENTS Principal Investigator & Institution: Levy, Robert J.; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Expandable metallic stents have been successfully utilized to relieve coronary arterial obstruction During this past year in the United States more then five hundred thousand coronary stents were used. Furthermore, there has been increasing interest in drug delivery stents to prevent restenosis following stent angioplasty. Our laboratory has pioneered the use of stents as platforms for gene delivery systems for arterial wall gene therapy. In this research program, we will address the following hypothesis: Gene therapy for in-stent restenosis and stabilization of vulnerable plaque can be achieved with a gene delivery stent. Our gene delivery stent utilizes antibody-mediated tethering of replication defective adenoviral gene vectors; this results in enhanced site specific ta'ansgene expression, and a highly localized biodistribution restricted to the site of stent deployment. Aims Aim 1: Polyaminobisphosphonate-steel interactions with subsequent polyamine and antibody binding: Formulation and Characterization. Bisphosphonate chemosorption will be the basis for a molecular surface modification of the steel stents either directly or with amplifying polyamines, to permit the covalent binding of anti-adenoviral antibodies to amino groups using bifunctional crosslinking, thereby enabling vector tethering. Aim 2: Formulation and characterization of the steel-PAABP-antibody gene delivery system: Ceil culture studies. Arterial smooth muscle cell cultures will be used as a model system to investigate the mechanism of gene delivery, fi-galactosidase (LacZ) and Green

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Fluorescent Protein (GFP) will be used as the reporter genes for these experiments. Aim 3: In vivo efficiency and anti-in-stent restenosis efficacy. Pig coronary stent studies will use the optimal formulations based on Aims 1 and 2. Reporter studies (LacZ) will focus on in vivo efficiency and biodistribution of vector. The therapeutic gene will be FasLigand, a pro-apoptotic protein with established efficacy for restenosis. The chief therapeutic endpoint will be extent of inhibition of neointimal formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN ANGIOTENSIN II RECEPTOR GENE REGULATION Principal Investigator & Institution: Elton, Terry S.; Chemistry and Biochemistry; Brigham Young University A-261 Asb Provo, Ut 846021231 Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 31-DEC-2005 Summary: Abnormal growth of vascular smooth muscle cells (VSMC) is central to the pathophysiology of various cardiovascular diseases such as atherosclerosis, hypertension and restenosis after angioplasty. These abnormalities can be manifested as changes in the state of VSMC proliferation, differentiation, gene expression patterns and morphology. Currently, the peptide hormone, angiotensin II (Ang II), is believed to play a pivotal role in the development of hypertension and atherosclerosis since it acts as a growth promoting factor in VSMC. The biological responses to Ang II are mediated by its interaction with two distinct high affinity G protein-coupled receptors (GPCRs) now designated AT1R and AT2R. While characterizing the human AT1R (hAT1R) gene, it was demonstrated that human tissues can express at least eight alternatively spliced hAT1R mRNA transcripts which differ only in their 5'-untranslated regions (5'-UTR). Currently, very little is known about the functional significance of each splice variant or how they are regulated. Therefore, the long term goals of this project are to functionally characterize each splice variant and to investigate the molecular mechanisms that govern the expression of these mRNAs. An understanding of these processes is critical since aberrant transcriptional, post- transcriptional and/or translational regulation of hAT1R gene expression may result in the over-expression of the hAT1R which would lead to exaggerated Ang II responsiveness and possibly result in cardiovascular disease. The Specific Aims of this proposal are to: 1) Test the hypothesis that hAT1R mRNA splice variants are differentially expressed in human tissues and investigate the transcriptional regulation of the hAT1R gene by the distal and proximal promoter regions, 2) Test the hypothesis that hAT1R mRNA splice variants have distinct mRNA half-lives, which can be regulated by physiological stimuli, 3) Test the hypothesis that hAT1R mRNA splice variants are translated with different efficiencies, 4) Characterize the internal ribosome entry site (IRES) harbored in exon-1 of the hAT1R mRNA 5'-UTR and identify trans-acting factors which recognize this element, and 5) Test the hypothesis that "long" and "short" hAT1R isoforms can form hetero-dimers and that these hetero-dimers are functionally distinct. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ID3 REGULATION OF SMOOTH MUSCLE CELL PROLIFERATION Principal Investigator & Institution: Mcnamara, Coleen A.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from Investigator's Abstract): Smooth muscle cell (SMC) proliferation plays a key role in a number of vascular proliferative disorders, including atherosclerosis and restenosis after balloon angioplasty. The long-term goal of this

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project is to identify the molecular mechanisms that regulate the growth state of SMC in response to vascular injury. The PI has demonstrated that Id3 (inhibitor of DNA binding), a helix-loop-helix (HLH) factor expressed in the vessel wall, enhances growth of SMC in culture potentially through inhibition of expression of the cell cycle regulator p21. He has recently cloned a novel Id3 isoform (Id3a) from a rat aortic SMC library and demonstrated unique vascular expression of this isoform relative to ID3. The Id3a mRNA retains a "coding intron," generating an ID3a protein with a unique carboxyl terminus. He has further shown that the C-terminus of ID3 is essential for its ability to block p21 gene expression. Thus,he hypothesizes that vascular injury regulates Id2 isoform expression resulting in functionally unique proteins that work in concert to regulate the SMC proliferative response. Aim 1 is to identify specific mechanisms by which Id3 enhances SMC proliferation and to determine the effect of Id3a on SMC growth. Studies will include: a) co-transfection studies to determine if Id3 and Id3a have effects on p21 transcription in SMC. Determine if Pan-1 can transactivate p21 in a SMC context and if Id3 and Id3a have effects on Pan-1 mediated p21 transactivation; b) Western analysis to determine if Id3a protein expression in SMC is regulated by serum or other mitogens; c) Id3a over-expression experiments to determine effects of Id3a on SMC proliferation and specifically on G1-S progression; d) cotransfection studies in p21 null cells to determine if there are Id3 and Id3a effects on proliferation that are p21 independent; e) cotransfection experiments to determine if Id3a is a dominant negative regulator of Id3; and f) domain swapping and mutagenesis studies to determine the amino acids in the C-terminus of Id3 that are essential for its dominant negative function in blocking gene transactivation in SMC and enhancing SMC proliferation. Aim 2 is to identify the mechanisms responsible for the differences in the basic functional properties between Id3 and Id3a. Studies will include: a) in vitro binding assays to determine if differences in dimerization interactions between Id3 and Id3a are responsible for their differential effects on transactivation; b) cotransfection studies using the mammalian two-hybrid system to determine if additional cellular factors are involved in regulating dimerization partner selectivity; c) electrophoretic mobility shift assays to determine if the above Id3/E-protein dimerizations are sufficient for inhibiting E-protein binding to an Ebox containing oligonucleotide; and d) domain swapping and mutagenesis studies to determine the amino acids in the C-terminus of Id3 that are essential for its altered ability to block E-protein binding to E-box containing oligonucleotides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMAGE-GUIDED INTERVENTIONS

TREATMENT

PLANNING

FOR

NEURO-

Principal Investigator & Institution: Hoffmann, Kenneth R.; Associate Professor; Neurosurgery; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Endovascular neurologic interventions are increasing in frequency and complexity. Devices are being placed above the Circle of Willis. Currently, interventionalists are judging accessibility via the proximal vessels using only subjective estimations from 2D angiograms. As a result, complication rates during procedures are as high as 10%. Calculation of the tortuosity of vessels can be performed from data extracted from computed tomography angiography (CTA), magnetic resonance angiography (MRA), and biplane or rotational angiograms, but the intervention a list also needs feedback of catheter position relative to the vasculature

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during the procedure. In addition, models are needed to estimate patient risk prior to placement. The goal of the proposed research is safer neuro-endovascular procedures, achieved by developing a system that can provide the interventionalist with information on vessel tortuosity, accessibility, device position, and potential complications during the procedure prior to and during device placement. Therefore, we propose to determine the hitherto unavailable quantities of curvature of, tortuosity of, and accessibility via the carotid, vertebral, and basilar arteries. Moreover, we will develop innovative, new techniques for estimating position and orientation of catheters, angioplasty balloons, and stents relative to vessel walls (proximity) and fusing this information with the vascular information for use during the procedure. With this information, we will develop models relating curvature, tortuosity, and proximity to complications so that the interventionalist can make more informed decisions regarding patient treatment involving interventional devices prior to and during attempts at placement, and thereby, reduce patient mortality and morbidity. With curvature and tortuosity available during interventional neurovascular procedures, coupled with relative 3D catheter positions and calculated probabilities of complications, we expect to improve access decisions as well as interventional device decisions. The impact of the proposed research is expected to lead to a substantial reduction of mortality and morbidity associated with neurovascular procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING HEALTH BEHAVIOR AND OUTCOMES AFTER ANGIOPLASTY Principal Investigator & Institution: Charlson, Mary E.; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (adapted from investigator's abstract): The principal objective of this randomized trial is to compare the effectiveness of two strategies for motivating behavioral change and improving two-year outcomes, survival free from myocardial infarction, stroke, Class II-IV angina or severe ischemia on non-invasive testing, among patients who have undergone angioplasty or coronary artery stent procedures. The will evaluate whether a novel behavioral intervention based on individualized feedback of risk profiles framed as the opportunity to reduce one's biologic age is more effective in reducing mortality and major cardiovascular morbidity than the standard risk reduction approach, which is framed as the opportunity to avoid future risk of morbidity and mortality. This new strategy is based on the economic theory of net-present value. A total of 660 patients who have completed angioplasty or stenting will be enrolled. Both the net-present value and standard treatment groups will receive a baseline risk evaluation. In both groups the potential areas for health risk behavior change are identical: physical activity, smoking, diet, blood pressure and medications. Control group patients will receive the standard post-procedure approach, which will include being shown their profile on 14 selected cardiovascular risk factors, relative to norms on each factor. They will be asked to choose 2-3 behaviors to change to increase their life span. Experimental group patients will receive their current biological age or "real age" based on their risk profile. They will be asked to choose 2-3 behaviors to change to reduce their biological age and shown the impact each behavior would have on biological age if maintained for 3 months and if maintained for 2 years. During the trial's maintenance phase, patients will be followed every three months, and at each follow-up will have their risk factor profile updated. The net- present value group will receive their updated biological age, and the control group will receive their updated risk factor

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profile. Final outcomes will be evaluated at two years. This trial is designed to test the effectiveness of the net-present value approach to improving health behavior and longterm outcomes after angioplasty or coronary artery stenting. The long-term objective of this study is to determine whether a net-present value approach for motivating behavior change is effective in improving treatment outcomes, and enhancing quality of life among a group of high-risk patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFLAMMATORY MARKERS AND CARDIOVASCULAR PATIENT OUTCOMES Principal Investigator & Institution: Frazier, Lorraine; Biological Sciences; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The candidate, an Associate Professor at the University of Texas Health Science Center at Houston (UT-Houston) School of Nursing, is currently a member of an interdisciplinary research team that conducts cardiovascular research. As a postdoctoral fellow in genetics and hypertension, she began participating in an NIH-funded Clinical Research Curriculum that she will complete during the proposed K Award. The long-term goal is to develop a model that will allow continued exploration of genetic, biochemical, and environmental risk factors in patients diagnosed with cardiovascular disease. Educational specific aims are to increase knowledge about cardiovascular disease that will stimulate new research hypotheses of the biochemical markers and related genes, and to increase knowledge in the design and analysis of large clinical cohort studies that will augment the quality of future grants. Environmental support available at UT-Houston includes laboratory support through the Human Genetics Center; educational support through the UT-Houston Medical School Clinical Research Curriculum; and access to patients, abstracting, and long-term follow-up through the TexGen Resource. The Award will support a pilot study to explore the prognostic value of inflammatory markers and related candidate gene variation to predict adverse outcomes in patients with cardiovascular disease. Specific aims of the research are to identify the prognostic value of: 1) novel biomarkers to predict the timing and severity of acute coronary syndrome (ACS), outcomes of: subsequent reperfusion interventions (stent placement, angioplasty, or cardiac bypass surgery), death, stroke, and myocardial infarction (MI), and to test for interactions with demographic/lifestyle and traditional clinical predictors; and 2) DNA sequence variation in the genes encoding the novel biomarkers identified in Aim 1, by assessing the interaction of the sequence variations and biomarkers to predict the timing and severity of the ACS outcomes of: subsequent reperfusion interventions, death, stroke, and MI, and to test for interaction with demographic/lifestyle and traditional clinical predictors. The proposed K award will allow the protected time needed to develop knowledge and skills in design, performance, and analysis of clinical research; to develop clinical knowledge of cardiovascular biomarkers; and to conduct the proposed pilot research in the Texas Medical Center. The pilot data will serve as preliminary data for an RO1 application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INHIBITION OF ANDROGEN RECEPTOR TO TREAT PROSTATE CANCER Principal Investigator & Institution: Devi, Gayathri R.; Avi Biopharma, Inc. 4575 Sw Research Way, Ste 200 Corvallis, or 97333

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Timing: Fiscal Year 2003; Project Start 19-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Prostate cancer is the second leading cause of cancer death in US men. Prostate cancer is highly dependent on androgen stimulation mediated through the androgen receptor (AR) for growth and proliferation. For those with advanced PCa, androgen ablation remains the foundation of therapy. Current methods of androgen ablation focus on diminishing circulating androgen or preventing androgen-AR interactions. Despite these efforts, almost all men progress to androgen independent (AI) PCa while on hormonal therapy. Interestingly, the AR continues to be expressed and is probably active in the majority of cases. However, no available therapy is known to interfere with AR function in AI PCa. This proposal focuses on using antisense technology to downregulate AR expression in androgen- independent PCa. AVI BioPharma has pioneered the development of phosphorodiamidate morpholino oligomers (PMOs), the third generation of antisense molecules that have overcome the limitations of earlier compounds. The PMO agents have been identified to be safe in a human Phase I study and are currently in late phase clinical trials for restenosis post coronary angioplasty, for polycystic kidney disease, and for a metabolic redirection trial. The long-term objective of this proposal is to determine the therapeutic value of inhibiting AR expression in human androgen-independent prostate cancer. Preliminary data in human LAPC-4 xenografts show that a PMO to the human AR can specifically and significantly downregulate AR expression along with reduction in prostate specific antigen (PSA) levels. PSA is a prognostic marker in PCa and is regulated by AR. Central Hypothesis: AR activation plays an important role in androgen-independent PCa, and downregulation of AR expression using the PMO-based antisense strategy is a novel mechanism-based therapeutic regimen for AI PCa. The specific aims of this proposal are: 1) To identify the PMO antisense sequence that maximizes in vivo human AR downregulation, while minimizing the non-antisense effects; and, 2): To determine the optimal dose and schedule of the PMO antisense identified in Aim 1 to downregulate AR in the murine PCa xenograft models. Based on these data, future pharmacokinetic and toxicology animal studies will allow proceeding to human phase I testing in a timely and efficient manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESTENOSIS

INTRACORONARY

CU-62

RADIATION

THERAPY

FOR

Principal Investigator & Institution: Lacy, Jeffrey L.; Proportional Technologies, Inc. Houston, Tx 77054 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-DEC-2003 Summary: Percutaneous transluminal coronary angioplasty (PTCA) has become the predominant treatment for symptomatic coronary atherosclerotic lesions. Despite its prevalent use, this technique continues to be plagued by restenosis rate of 40% with resultant enormous added health care costs and patient morbidity. Radiation therapy applied locally at the site of coronary balloon injury holds great promise to reduce this restenosis rate. All current and proposed techniques of radiation delivery carry significant drawbacks of safety and effectiveness of uniform dose application. This project proposes a unique, novel approach to radiation delivery through utilization of short-lived positron emitting isotope, Cu-62, produced by a generator system. This isotope is delivered into the angioplasty balloon and provides the required radiation with a brief and safe inflation time. Safety issues are addressed through use of a Cu-62 chemical form assuring blood binding in the event of balloon rupture combined with the short 9.7 minute half-life of Cu-62. Use of a balloon provides significant advantages of

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uniformity of dose delivery and with Cu-62 is completely safe. In Phase I, an automated concentration system was developed which coupled to the Zn-62/Cu-62 generator produced the highly concentrated solution of Cu-62. This concentrator was employed in porcine overstretch injury model of restenosis, which demonstrated the feasibility of safe use of generator produced Cu-62 and also achieved a substantial reduction of neointimal hyperplasia using a delivered dose of 25 Gy. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IRON MEDIATED CARDIOVASCULAR INJURY Principal Investigator & Institution: Horwitz, Lawrence D.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-JAN-2003 Summary: Iron plays a critical role in two processes of great importance in cardiovascular diseases: vascular smooth muscle proliferation and reperfusion injury. We have isolated, synthesized and completed highly promising pilot studies on a family of iron chelators,exochelins secreted by Mycobacterium tuberculosis. They block redox reactions and are unique among chelators in that they are lipid soluble, a property that permits them to rapidly enter cells and be physiologically active at extremely low concentrations. In the desferri-form, exochelins prevent damage by reactive oxygen species to cultured cardiac myocytes, reperfusion injury in isolated rabbit hearts and proliferation of cultured human vascular smooth muscle cells (VSMCs). We propose to elucidate the molecular mechanisms by which iron chelation with lipid-soluble exochelins prevent VSMC growth. In cultured human VSMCs we will test the hypothesis that exochelins block progression through the cell cycle at both the G1 and S phases by inhibiting activity of cyclin-dependent kinases. We propose that this occurs through upregulation of inhibitory proteins, particularly p21. We will examine the uptake and intracellular distribution of exochelins and the extent to which they influence VSMC growth through interruption of redox signaling. In separate studies we will assess whether exochelins given intramurally or intracoronary will prevent coronary artery restenosis due to VSMC proliferation following angioplasty in a porcine model. We will also assess the effects of desferri-exochelins given during reperfusion on myocardial infarct size, normalized for volume at risk and collateral blood flow, in a rigorous canine model involving 90 min of coronary occlusion and 48 hours of reperfusion. Finally we will examine whether desferri-exochelins prevent apoptosis, a genetically programmed mechanism of cell death that has been associated with reperfusion injury. We believe that exochelins have extraordinary potential for prevention of vascular and reperfusion injury, and are uniquely suitable for understanding the role of iron in these processes. This project would offer important mechanistic information at the molecular level and critical potential proof of principle for important therapeutic applications. We submit that our considerable progress to date and our unique familiarity with exochelins establishes that we have the capabilities to complete these exciting studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISCHEMIC BRAIN DAMAGE & TRIPLE/SINGLE QUANTUM SODIUM MRI Principal Investigator & Institution: Boada, Fernando E.; Associate Professor; Radiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The main thrust for this project is the validation of quantitative sodium MRI as a non-invasive means for estimating tissue viability during focal stroke using MRI. Stroke is a major public health concern in the United States. The introduction of reperfusion therapy using tissue plasminogen activator (tPA) revolutionized the treatment of stroke by providing an aggressive means to reverse the ischemic insult. The effectiveness of tPA reperfusion therapy is highly dependent on the status of the ischemic mass. Specifically, when the ischemic tissue is viable, use of tPA leads to improved clinical outcome. However, when the ischemic tissue is non-viable, reperfusion therapy can lead to intracerebral hemorrhage and/or an accelerated rate of ischemia formation. These in turn, can lead to increased intra-crannial pressure and a concomitant compromise of blood flow in areas not affected by the initial insult. Currently, there are no well-accepted, non-invasive means to assess tissue viability in stroke and, therefore, there are no direct measures to unambiguously gauge the relative benefits of the tPA therapeutic option prior to its application. Perfusion and diffusion weighted proton MRI (DW MRI) are well-established techniques for the early detection of brain ischemia. However, there is no direct correlation between measures of perfusion and/or diffusion MRI and the viability of the ischemic brain tissue. By contrast, tissue sodium concentration (TSC) exhibits a linear and reversible response for many hours after ischemia onset. Because sodium accumulation in tissue is closely related to its metabolic status, these findings have two immediate implications. First, ischemia duration should be linearly dependent on the measured TSC, and, second, there should be a threshold in TSC below which tissue reperfusion should lead to improved clinical outcome. To test the validity of these hypotheses we will perform sexual single and triple quantum filtered sodium MRI scans in a non-human primate model of temporary middle cerebral artery (MCA) occlusion. The use of a primate model of MCA occlusion will allow the study of the temporal and spatial distribution of the TSC accumulation and its relation to the deficits in cerebral blood flow. We believe that the findings from this research will provide important data that could lead to the development of useful guidelines for the clinical! management of acute stroke when sodium MRI is used in conjunction with diffusion and perfusion MRI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ACUTE VASCULAR REACTION TO INJURY Principal Investigator & Institution: Schwartz, Stephen Mark.; Associate Member; Pathology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-MAR-1973; Project End 31-JUL-2003 Summary: This application is for competitive renewal of the Program Project "Mechanisms of Acute Vascular Reaction to Injury". This long-standing program has made seminal contributions to our understanding of the origins of the arterial intima and the formation of atherosclerotic lesions in the intima. Critical contributions in the past include demonstrations of monoclonality, development of the standard "three wave" model for formation of an intima after angioplasty, cloning of intimal-specific genes, and identification of growth factors required for formation of the intima. These interests continue to be pursued in the renewal. Two projects (Projects 1 and 2) focus on mechanisms of apoptosis in endothelial and smooth muscle cells, including the proapoptotic caspase pathway and anti-apoptotic pathways mediated by bcl-2 homologues. The focus in Project 1 is on model systems designed to explore the role of apoptosis in the failure of vessels to accommodate growth of atherosclerotic plaque. Project 2 focuses on apoptotic resistance, primarily in endothelial cells, mediated by cytokines that can

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Angioplasty

protect as well as kill. Project 6 uses innovative chimeric animals and a genetically engineered intima to study, for the first time, the role of endogenous growth factors. The same technology is used in several of the other projects, especially to address issues of the biology of pre-existing intima. We know how an intima is formed, but pathologic responses occur in a pre-existing intima. In Project 4, the critical issue is understanding the response to growth factors once an intima is already formed. Project 5 also looks at the intima, studying the role of integrins in forming the intima and role of an intimalspecific gene, osteopontin in determining intimal function. Finally, our knowledge of how the intima is formed has begin to be useful to another area developed during our last funding period--the repair of injured myocardium. Our previous Project 3 explored cardiac cell differentiation. Project 3 in this competitive renewal uses that information as well as tools from our work on the formation of intima, especially genetically engineered cells, to attempt to recreate sarcomeric muscle in the myocardium. These six projects are supported by a Core that assists in analysis of tissue and development of animal models, and by an Administrative Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICRONEEDLE ARRAY FOR CATHETER DRUG DELIVERY Principal Investigator & Institution: Roy, Shuvo; Co-Director, Biomems Laboratory; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The ultimate goal of this project is the development of a catheter that can inject drugs directly into the wall of the coronary artery to prevent restenosis after angioplasty. MEMS (microelectromechanical systems) technology will be used to prototype miniature hollow needles from silicon substrates. Microneedle arrays will be integrated with low profile catheter delivery systems for transport to and from the deployment site within arteries. Finite element modeling will be used to generate robust needle designs, which will be subsequently fabricated using deep reactive ion etching and wet anisotropic etching of silicon. Different microneedle geometries and array layouts will be fabricated and evaluated for mechanical strength and penetration characteristics into filleted rabbit lilac and porcine coronary arteries. Two low profile catheter delivery systems will be developed to transport the microneedle array to the coronary artery. One approach will rely on a low profile balloon to house the microneedle array inside molded pockets within the balloon. The other approach will investigate a novel suction catheter that would house the microneedle during transport. Once at the deployment site within the artery, suction would be applied via a syringe to pull the vascular wall towards the catheter and force the microneedles into the tissue. Fluid delivery will be demonstrated by injecting Evan's Blue dye into the arterial wall. Experiments and computer modeling will be conducted to optimize the microneedle geometry and array layout for penetration and fluid delivery. Results of this R21 project will establish the feasibility for further development of microneedles for local drug delivery catheters that could be used to investigate the efficacy and delivery characteristics of anti-restenosis therapy delivered directly into the vascular wall. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION OF INTEGRIN FUNCTION BY THE UROKINASE RECEPTOR Principal Investigator & Institution: Zhang, Li; Scientist Ii; American National Red Cross Rockville, Md 20855

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Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: Wound healing is a dynamic process involving multiple coordinated events, including recruitment of leukocytes to the injury site, removal of the provisional matrix and cell debris, production of cytokines and growth factors, cell and matrix regeneration, etc. A number of in vitro and in vivo studies have provided strong evidence for the involvement of leukocytes, the fibrinolytic system (Plg, uPA, uPAR and Fg), have alphabbeta2 integrin, and the endocytic pathways (e.g. LRP) in wound healing is currently unknown. Given the paramount importance of wound healing and the fact that dysfunction of wound healing contributes to many chronic diseases such as atherosclerosis associated with myocardial infarction and stroke, restonosis after angioplasty, and rheumatoid arthritis, the long term goal of this laboratory is to understand the molecular mechanisms underlying the wound healing process. Toward this goal, we have initially focused on the interactions of ampha4beta2 with Fg and uPAR, and identified partial sequences that mediate these interactions. Since many cell types produce both uPA and PAI-1 in response to injury, and the PAI-1-uPA complex, and thereby participate in wound healing by modulating alpha2beta2-mediated monocyte cell migration and fibrin degradation. We will test this hypothesis by identifying the binding interface between alpha2beta2 and uPAR, using our established homolog-scanning mutagenesis approach, and study the mechanisms by which uPAR and LRP modulate the functions of alphambeta2. The importance of the alpha4beta2/uPAR/LRP system in vivo wound healing will be tested by reconstituting this system in alphambeta2- and uPAR-deficient mice, as well as monocyte specific LRPdeficient mice, using bone marrow transplant technology and transgenic technology. Overall, these studies will provide insight into the mechanisms and functional consequences of the alphaMbeta2/uPAR/LRP interactions in wound healing. Such information will not only help us understand the physiology of the fundamental process, it may also assist in the development of new strategies and therapeutic interventions that will block the pathogenesis of many diseases, such as myocardial infarction, stroke, and rheumatoid arthritis, as well as tumor growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BARRIERS TO THROMBOSIS ON TISSUE SURFACES Principal Investigator & Institution: Wagner, William R.; Deputy Director, Mcgowan Institute for r; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from the applicant's abstract) This project seeks to develop and investigate methods to inhibit platelet deposition onto damaged arterial surfaces by reacting polymer segments with surface proteins exposed at sites of tissue damage. The investigators hypothesize that covalently attached polymer segments will sterically inhibit cell receptor interaction with adhesive surface ligands, thus reducing platelet deposition. Preliminary data indicates that polyethylene glycols (PEGs) with end groups reactive toward proteins can be applied to damaged arterial segments under conditions and times which would be applicable in a clinical setting. Further preliminary data shows that such covalently attached PEG segments inhibit acute platelet deposition onto these damaged human arterial segments in vitro and in balloon damaged rabbit femoral arteries in vivo. The proposed experimentation will focus on developing and refining methods for the creation of molecular barriers to thrombosis on damaged arterial surfaces, since intravascular thrombosis and the physiologic responses it potentiates remain obstacles to the success of a variety of vascular procedures and create

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widespread clinical morbidity and mortality. The molecular barrier technology will be developed specifically by first determining the degree of covalent PEG attachment achievable to model adhesive proteins and damaged arterial tissue surface in vitro, (under conditions tolerable in vivo). The influence of reactive PEG chemistry on this attachment will be studied. The ability of various molecular weights and surface concentrations of covalently attached PEGs to inhibit platelet deposition on to adsorbed adhesive proteins and damaged arterial surfaces will be examined. Finally, studies will be performed in a rabbit model to examine how covalent PEG attachment can interrupt acute thrombotic deposition following balloon arterial damage, prevent neointimal hyperplasia exacerbated by this acute thrombosis, and prevent restenosis following balloon angioplasty of a stenotic lesion. At the completion of this project, the investigators hope to understand how molecular parameters of tissue reactive PEGs affect the formation of molecular barriers to cell-tissue interactions. They also hope to have developed and tested a novel strategy for inhibiting acute cell-tissue interactions and plan to have specifically examined the ability of this technique to address the important clinical problem of arterial thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MRI-GUIDED ANGIOPLASTY OF RENAL ARTERY STENOSIS Principal Investigator & Institution: Omary, Reed A.; Assistant Professor of Radiology; Radiology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The objective of this proposal is to support the applicant's development of an independent research program focusing on new treatment methods for renal vascular disease with magnetic resonance imaging (MRI) guidance. The candidate's immediate career goals are to gain animal research experience, learn and advance MRI techniques, and enhance clinical skills as an interventional radiologist. The candidate's long-term career objective is to become an active independent biomedical researcher. He aims to improve patient care by expanding the boundaries of MRI from a diagnostic imaging to a treatment guidance modality. To develop his research career, the candidate proposes learning: 1) fundamental MRI techniques related to blood vessel imaging and intervention, 2) swine experimental methods, and 3) methods for the responsible conduct of research. These skills will be acquired through a combination of coursework, MR technique workshops, weekly conferences, independent study, and interaction with sponsors/ advisory committee at Northwestern University Medical School. Sponsors include Drs. J. Paul Finn, Debiao Li, and Robert Vogelzang. The advisory committee also includes Drs. Dieter Enzmann and Francis Klocke. The broad, long-term objective of the research plan is to improve the prognosis of patients with renal vascular disease. In swine, the proposal aims to test the hypotheses that: 1) Intra-arterial gadolinium-enhanced magnetic resonance angiography (MRA) depicts renal arterial lumen caliber as accurately as x-ray angiography; 2) The technical success rate, complication rate, and procedure time for MRI-guided and x-ray guided percutaneous transluminal balloon angioplasty (PTA) of renal artery stenosis are similar; and 3) Successful MRI-guided PTA of renal artery stenosis improves kidney function as measured with MRI at the time of the procedure. If these hypotheses are shown to be correct, then the success and safety for MRI-guided PTA of renal artery stenosis will be confirmed. MRI will be useful to monitor immediate changes in kidney function at the time of renal artery PTA, an added value that cannot be performed using x-ray guidance. MRI guidance will also

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avoid the ionizing radiation exposure of x-rays and the potential kidney toxicity of iodinated contrast agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NO/CGMP SIGNAL TRANSDUCTION SYSTEM IN VASCULAR INJURY Principal Investigator & Institution: Bloch, Kenneth D.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The objective of this proposal is to characterize the roles of nitric oxide (NO)/cGMP signal transduction in the neointimal response to vascular injury. Vascular injury induces smooth muscle cells in the media to migrate into the intima, where they proliferate and synthesize extracellular matrix, ultimately compromising the lumen. Recent studies in animal models and in patients with coronary artery disease have suggested that increasing NO levels at the site of vascular injury inhibits neointima formation. NO acts, in part, by stimulating soluble guanylate cyclase (sGC), a heterodimer composed of alpha and beta subunits, to produce cGMP leading to activation of cGMP-dependent protein kinase Z(cGDPK). In vitro, NO appears to modulate many vascular cell functions, inhibiting smooth muscle cell proliferation, migration, and extracellular matrix synthesis and stimulating endothelial cell proliferation and smooth muscle cell apoptosis. Preliminary evidence suggests that sGC and cGDPK are decreased in neointimal smooth muscle cells of injured blood vessels. We hypothesize that vascular cell NO/cGMP signal transduction has an important role in attenuating neointima formation and that decreased sGC and cGDPK limit the ability of NO to inhibit neointima formation. To test these hypothesis, adenovirus-mediated gene transfer will be used to determine the effect of altering NO/cGMP signal transduction on the neointimal response to vascular injury. In Specific Aim 1, vascular cells in culture will be infected with adenoviral vectors specifying a mutant dominantnegative sGC alpha1 subunit, wild-type cGDPK, and a mutant constitutively-active cGDPK. The effects of altering NO/cGMP signal transduction on vascular cell functions which contribute to neointima formation will be identified. In Specific Aim 2, sGC and cGDPK expression will be correlated with the changes in vascular cell functions associated with balloon-induced vascular injury in a rat carotid artery model. In Specific Aim 3, adenovirus-mediated gene transfer will be used to investigate the effect of modulating NO/cGMP signal transduction on vascular injury-induced neointima formation, as well as re- endothelialization, and smooth muscle cell proliferation, apoptosis and extracellular matrix synthesis. Neointima formation contributes to the restonosis process which frequently follows percutaneous angioplasty. Understanding the roles of the NO/cGMP signal transduction system in modulating the response to vascular injury may provide novel therapeutic approaches for the treatment of restonosis that percutaneous angioplasty. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NON-INVASIVE IN-STENT RESTENOSIS DETECTOR Principal Investigator & Institution: Esch, Victor C.; Cardioheart Systems 6248 Preston Ave Livermore, Ca 94551 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): The goal of this proposal is to evaluate two noninvasive techniques for detecting in-stent restenosis and based on the results design a

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compact clinical device that can be used in a doctor's office. An estimated seven million American suffer from coronary artery disease, which causes 1.5 million myocardial infarctions. Currently, the preferred treatment to open occluded arteries is a combination of angioplasty and stenting. This combination has over the past years significantly reduced the occurrence of restenosis in the treated area. Yet, restenosis rates can still be as high as 25% in high-risk populations. Current techniques for detecting restenosis include coronary angiography, radionuclide ventriculography, and intravascular ultrasound. These techniques are expensive, time consuming, and invasive. Our proposed takes advantage of the fact that the dielectric properties of blood and plaque can differ by as much as an order of magnitude over the frequency range extending from 100 MHz to 10GHz. Consequently, the electromagnetic scattering spectrum of a stent will change as plaque forms. By measuring this change over time we expect to identify potentially dangerous restenosis. This type of device is only now practical because of significant advance in wireless communication technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL COLLAGEN-BASED PERIPHERAL ENDOPROSTHESIS Principal Investigator & Institution: Li, Shu-Tung T.; President & Ceo; Collagen Matrix, Inc. 509 Commerce St Franklin Lakes, Nj 07417 Timing: Fiscal Year 2002; Project Start 15-SEP-1999; Project End 31-JUL-2003 Summary: (Verbatim from the Applicant's Abstract): Despite the wide acceptance of percutaneous transluminal angioplasty (PTA) and intravascular stenting for treating patients with peripheral atherosclerotic lesions, these techniques suffer some drawbacks, which, limit their overall clinical success. A high rate of restenosis remains the major complication of PTA and intravascular stenting procedures. The overall goal of this research is to design, develop and test in vivo a novel collagen-based endoprosthesis (CBE) for reducing the rate of post-PTA restenosis. In the phase I investigation, we have designed and developed a CBE prototype that can be reliably delivered by standard transluminal percutaneous intervention techniques. The CBE prototype had a superior patency rate compared to an ePTFE vascular graft-based endoprosthesis prototype in a canine femoral artery model. In the phase II, we will further improve the design of the CBE, and evaluate the in vivo performance of the CBE in an atherosclerotic animal model. Upon completion of the phase II research, we will continue the phase III program and actively pursue clinical trials and commercialization of the CBE device. PROPOSED COMMERCIAL APPLICATION: There were more than 150,000 percutaneous transluminal angioplasty (PTA) procedures performed to treat patients with peripheral atherosclerotic lesions in the U.S. in 1995 alone. The occurrence of late restenosis typically lead to reinterventions that result in a significant increase of the total costs of patient care. If the proposed endoprosthesis device functions well, a 5% reduction of the restenosis rate can be translated into a savings of more than $100 million dollars a year in the associated healthcare costs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OCCLUDED ARTERY TRIAL DATA COORDINATING CENTER Principal Investigator & Institution: Knatterud, Genell L.; President; Maryland Medical Research Institute, Inc 600 Wyndhurst Ave Baltimore, Md 21210 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Current pharmacologic strategies fail to achieve effective reperfusion in 30 percent or more of acute myocardial infarction (MI) patients, and many patients with

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occluded infarct-related arteries (IRAs) do not meet current criteria for use of these agents. Early angioplasty, an effective reperfusion method, is available to a small proportion of potentially eligible acute MI patients in the U. S. Hence, a substantial number of acute MI patients pass the time when reperfusion therapy has well documented benefit (12-24 hours) with a persistently closed IRAs. Several lines of experimental and clinical evidence suggest that late reperfusion of these patients could provide clinically significant reductions in mortality and morbidity. Hypothesis. Opening an occluded IRA 3-21 days after an acute MI in high-risk asymptomatic patients (ejection fraction less than 50 percent or proximal occlusion of a large coronary artery) will reduce the composite end point of mortality, recurrent MI, and hospitalization for NYHA Class IV congestive heart failure (CHF) over an average 3year follow-up. Study aims. In the Open Artery Trial (OAT) 3,200 patients will be randomly allocated in equal proportions to the two treatments over two years. One treatment will consist of conventional medical management (including aspirin, beta blockers, ACE inhibitors, and risk factor modification). The experimental treatment will consist of conventional medical therapy plus percutaneous coronary intervention and coronary stenting. The primary specific aim is to compare the composite outcome of allcause mortality, non-fatal MI and hospitalization for Class IV CHF based on an average 3-year follow-up among patients assigned to the two treatments. Three secondary specific aims are to compare: 1) the individual components of the study composite primary end point in the two treatments; 2) the medical costs of the two treatments; and 3) health-related quality of life in the two treatments. Role of Data Coordinating Center. This application is made for support of a Data Coordinating Center (DCC) at the Maryland Medical Research Institute. The DCC is responsible for statistical design and power calculations, random treatment assignments, data management, support for the Mortality and Morbidity Classification Committee, rapid communication and generation of performance data for review with the Study Chair and Co-Chair of the Clinical Coordinating Center and data analysis to assess treatment effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLD AGE, LIFE EXTENSION, AND GERIATRICS Principal Investigator & Institution: Kaufman, Sharon R.; Professor; Institute for Health and Aging; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The goal of this 4-year qualitative anthropological study is to investigate first, how physicians, patients age 70 and over and their families make decisions regarding the use of three groups of life-extending medical procedures (cardiac bypass, angioplasty and stent; kidney and liver transplant; and renal dialysis) and how they each respond to those procedures; and second, to identify socio-cultural issues of relevance to physicians and to society regarding the growing use of lifeextending medical procedures on elderly patients. This will be an empirical, ethnographic study based on the collection of data by in-depth interviews with physicians, patients and their families, and by participant-observation of support groups for cardiac and transplant patients and of physician-patient discussions where lifeextending procedures are discussed. There are 4 specific aims:1) to provide a descriptive account of physician, patient, and family understandings of relationships among changing conceptions of old age, health in late life and expectations about life-extending medical care; 2) to learn how physicians in different specialties are extending the lives of their elderly patients and the values underlying their decisions; 3) to learn the structural

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Angioplasty

and cultural constraints on their choices for life-extending procedures; and 4) to describe patient and family choices, knowledge and values. Coding-based qualitative data analysis will be used: cross-sectional comparison, thematic analysis, case studies, and frequencies of response. The interpretive goal is to examine in detail the social, structural and medical practices and values brought to bear on the extension of life at progressively older ages. This will be the first research that comprehensively addresses medical and lay decision-making surrounding life-extending medical procedures for older persons, and the responses and experiences of physicians, patients and families to those procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GUIDEWIRE

OPTICAL

PRESSURE

SENSOR

BUILT

IN

ANGIOPLASTY

Principal Investigator & Institution: Sawatari, Takeo; Sentec Corporation 2000 Oakley Park Rd, Ste 205 Walled Lake, Mi 48390 Timing: Fiscal Year 2002; Project Start 20-JAN-1999; Project End 31-JUL-2004 Summary: (Unedited Applicant's Abstract): The development of an ultra-miniature optical pressure sensor is proposed for NHLBI's research topics: Heart and Vascular Diseases, Biosensors. Intended for intravascular use, the sensor must be disposable and, therefore, will be designed to be available at a reasonable cost for clinical use. The small size of the sensor and the flexibility of the optical fibers will result in a pressure transducer, which can be inserted into blood vessels (arteries, veins, or heart chamber) with an angioplasty guide wire with a diameter of only 0.3 mm. The sensor can measure blood pressures in the range of 0 to 300 mmHg with both diastolic and systolic blood pressures. The sensor will operate over time periods of up to a few days without periodic re-calibration. Its pressure readings will be independent of temperature changes in the range of 20 degreesC - 50 degreesC. The primary commercial application of this device will be for angioplasty treatment. Because of its small size, the sensor can be used for infants and also to monitor fluid pressures in the human brain after surgery. The low cost will allow it to be used for small animal research. The Phase I effort demonstrated the feasibility of the proposed approach. Prototype development will be carried out in Phase II. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND HEMODIALYSIS ACCESS FAILURE Principal Investigator & Institution: Weiss, Miriam F.; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Antioxidant treatment of human disease has met with mixed success. Factors that lead to oxidative stress in living systems are complicated, and as a result, the actions of antioxidants may seem paradoxical. There is a great deal of evidence for increased oxidative stress in uremia. The rationale for this proposal stems from emerging evidence for efficacy of vitamin E in uremia. The investigators believe that intimal hyperplasia in hemodialysis vascular access represents a unique model of oxidative damage to vascular tissue. Complications of hemodialysis access are a major cause of morbidity and the most frequent single reason for hospitalization among patients with end stage renal disease (ESRD). In vivo and in vitro, oxidative stress stimulates cell growth factors and regulatory mechanisms that lead to the characteristic lesion of access failure, intimal hyperplasia. The central

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hypothesis to be tested by this project is that oxidative stress is a major (and modifiable) pathogenetic trigger for vascular access complications in patients with ESRD. In elucidating the roles of oxidative stress in the pathophysiology of access failure, the goal is to discover diagnostic factors that can lead to accurate indications for antioxidant therapy. In testing antioxidant medication, the investigators hope to slow progression of intimal hyperplasia in hemodialysis access. Because antioxidant therapy is not currently routine in patients with uremia, the proposal is a pilot study. Data obtained in these specific aims will be used to design large-scale testing of the efficacy of vitamin E (alpha-tocopherol). Specific Aim A: To identify predictors of vascular access venous outflow stenosis or thrombosis, focusing on circulating and histologic markers indicative of the effects of oxidative stress. Specific Aim B: To determine the efficacy of chronic administration of an antioxidant (alpha-tocopherol) in the prevention of intimal hyperplasia and thrombosis of the hemodialysis access. Specific Aim C: To compare the success rates of prophylactic angioplasty when non-invasive techniques demonstrate decreased flow in the hemodialysis access in alpha-tocopherol-treated versus placebotreated patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARP INFARCTION

INHIBITOR

THERAPY

FOR

ACUTE

MYOCARDIAL

Principal Investigator & Institution: Salzman, Andrew L.; Inotek Pharmaceuticals Corporation 100 Cummings Ctr, Ste 419E Beverly, Ma 01915 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Despite the established benefits of reperfusion therapy among patients presenting with ST elevation myocardial infarction (STEMI), restoration of flow to the injured myocardium appears to be associated with a number of deleterious effects, including microvascular injury, arrhythmias, and extension of myocyte necrosis. The disruption of intracellular energetics and inflammatory processes triggered by the rapid generation of oxidant molecules appear to play a central role in the consequent myocyte injury. Oxidant-induced DNA single strand-breakage activates the nuclear enzyme poly (ADP-ribose) polymerase (PARP) and initiates an energy consuming, inefficient cellular metabolic cycle. The resultant depletion of dinucleotide pools slows the rate of glycolysis and mitochondrial respiration, reducing ATP synthesis and leading to cellular dysfunction and necrosis. Utilizing our proprietary PARP inhibitor INO-1001 (Ki=15 nanomolar), we have demonstrated that PARP inhibition reduces myocardial infarction by 65 percent in pigs with acute STEMI induced by left coronary arterial ligation. The central objective of the proposed Fast Track application is to establish the clinical efficacy of INO-1001 as a potential adjunctive therapy for STEMI in the setting of primary percutaneous coronary intervention (angioplasty or stenting). In the PHASE 1 SBIR we will establish the role of PARP in the regulation of cellular dysfunction and inflammatory response in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). In a prospective, multi-center, randomized, open-label, dose-ranging investigation we will study 45 human volunteers with acute anterior or inferior MI undergoing primary PCI. The trial will be conducted in 10-15 American hospitals, led by the Chairman of the TIMI Study Group, Professor Eugene Braunwald. INO-1001 therapy at two dose levels (or placebo) will be administered before the initiation of reperfusion therapy (primary PCI), i.e., prior to the onset of I/R injury. We expect these studies to demonstrate (a) that INO-1001 dose-dependently inhibits cellular PARP activity in patients with STEMI, and (b) that the pharmacokinetics of INO-1001 in STEMI patients are comparable to those in healthy human volunteers.

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Angioplasty

These studies will provide the scientific foundation for a PHASE 2 SBIR funded 330 patient, multicenter, TIMI-led investigation to establish the efficacy of INO-1001 in reducing infarct size in patients acutely presenting with STEMI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOGENETIC ANTIPLATELET STRATEGIES IN CHD PATIENTS Principal Investigator & Institution: Cooke, Glen E.; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 22-JAN-2003; Project End 31-DEC-2007 Summary: (provided by the applicant):Coronary heart disease (CHD) remains the most important cause of mortality. Myocardial infarction and unstable angina result from formation of a platelet thrombus, a process that requires the binding of extracellular adhesive ligands to the GPIIb-IIIa receptor on the surface of platelets. Percutaneous transluminal coronary angioplasty (PTCA/stenting) also results in disruption of vessel integrity at the location of an atherosclerotic plaque and during and after these procedures (up to thirty days, currently), there is an absolute requirement for antithrombotic therapy. The GPIlb-IIIa receptor is known to be polymorphic and the presence of the PLA2 allele has been associated with an increased prevalence of ischemic syndromes, especially in younger individuals. Recently, the PLA2 polymorphism has emerged as an important risk for sudden coronary death in patients less than 60 with myocardial infarction and adverse events in patients undergoing coronary stenting. Numerous studies have reported varying results with regard to this novel risk factor. It is fair to say that, as a result of divergent results generated by these subsequent studies, two camps have emerged: those who believe that PLA2 is a risk factor for arterial thrombosis, and those who do not. Our ability to interpretepidemiological data is limited by the lack of understanding of the effect of the PLA2 polymorphism on platelet biology and thrombosis. We have previously demonstrated that a differential effect of aspirin (ASA) on platelet aggregation occurs in platelets that demonstrate the PLA2 polymorphism, which may in part, explain the divergent results of PLA and CHD in numerous studies. We have conducted a study to characterize the impact of PLA2 on platelet response to agonists, in patients with CHD, randomized to receive ASA, (325mg/day), clopidogrel (75mg/day) or a combination of ASA and clopidogrel. We have shown that PLA functions as an important modifier for the platelet response to ASA, clopidogrel or their combination in CHD patients. ASA+clopidogrel appears superior than ASA alone in reducing platelet aggregation. Our data suggest that responses to clopidogrel and ASA, both, are PLA sensitive. The synergy between ASA and clopidogrel in PLA 1/A2 patients is interesting and could involve ASA inhibition of COX-1. However, when administered at 325mg per day, a contribution of COX-2 inhibition to this synergistic effect is possible. The overall hypothesis of this proposal is that genetics, and specifically the PLA2 polymorphism, can be used to determine optimum antiplatelet therapy in patients with CHD. This will be tested in patients with CHD, post-stent, by randomizing them to receive either ASA, clopidogrel, or ASA and clopidogrel and assessing clinical and platelet functional endpoints as a function of PLA. In addition, to expand our understanding to novel mechanisms of antiplatelet therapy we will also assess the potential benefit of COX-2 inhibition with a specific COX-2 inhibitor, rofecoxib. Such information will be paramount in the targeting of antiplatelet therapies and will be based on genomlc information (pharmacogenetics). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION OF HEMODIALYSIS VASCULAR ACCESS STENOSIS Principal Investigator & Institution: Cheung, Alfred K.; Professor of Medicine; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Neointimal hyperplasia is a frequent cause of stenosis in blood vessels and is commonly observed in post-angioplasty coronary arteries and hemodialysis vascular accesses. In native arteriovenous (AV) fistulae and polytetrafluoroethylene (PTFE) grafts for hemodialysis, the stenosis is usually focal and occurs at the AV or graft-venous anastomosis. Effective strategies for the prevention of stenosis are lacking. We hypothesize that local delivery of anti-proliferative drugs and anti-growth factor antibodies using a novel drug delivery system, ReGel, will inhibit neointimal hyperplasia associated with native AV fistulae and PTFE grafts. ReGel is an injectable, thermosensitive copolymer designed for local, sustained-delivery of drugs. This is a multidisciplinary approach to address the following specific aims: (1) To examine the efficacy of two anti-proliferative drugs (dipyridamole or paclitaxel) and anti-platelet derived growth factor (PDGF) antibodies alone or in combinations in the inhibition of growth of human or canine vascular smooth muscle cells. These in vitro studies will set the stage for animal studies in this proposal and potential clinical trials in the future. (2) To study the release kinetics of the anti-proliferative drugs and antiPDGF antibodies from ReGel in vitro and their transport kinetics across explanted native AV fistulae and PTFE grafts. The transport characteristics of the drugs and antibodies in ReGel applied to the perivascular area of the native AV fistula and PTFE graft around the venous anastomosis will then be evaluated in whole dog experiments. Comparisons of mathematical model predictions with results from these experiments will help optimize the therapeutic dose of drugs and antibodies and conditions for delivery by ReGel in vivo. (3) To examine the efficacy of the anti-proliferative drugs and anti-PDGF antibodies delivered by ReGel in inhibiting neointimal hyperplasia in dog models of native AV fistula and PTFE graft. Successful development of this technique will provide a novel approach of local drug delivery to prevent neointimal hyperplasia and stenosis in blood vessels. Furthermore, the results will provide the basis for local delivery of drugs and proteins of interest to a variety of tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PULSATILE HEMODYNAMICS AND CAROTID STENTING Principal Investigator & Institution: Quick, Christopher M.; Veterinary Physiology & Pharmacology; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Angioplasty and stenting of the large conductance vessels that supply the brain is a relatively new treatment that may be a viable alternative to carotid endarterectomy. Based on the extensive history of coronary artery stenting, it can be surmised that restenosis will be a key factor limiting the long-term success of carotid arterial stenting. The hemodynamic factors that influence restenosis, especially pulsatile pressure and flow, have received little scrutiny. We hypothesize that the degree of in-stent restenosis is related to pulsatility of pressure and flow. The following four specific aims will address this hypothesis: 1) To measure the degree of restenosis after carotid artery stenting and associated changes in pulsatile blood pressure and flow; 2) To predict with a patient-specific computational model the short and long-term changes in pulsatile pressure and flow after stenting; 3) To compare restenosis in rabbit iliac arteries that are subjected to high and low levels of pulsatile

46

Angioplasty

pressure and flow; 4) To compare remodeling factors in chronically stented vessels subjected to high and low levels of pulsatility. Dr. Quick is an engineer who has an extensive background in computational modeling of pulsatile hemodynamics in vascular beds. Funding is sought for a five-year training periodfor Dr. Quick to transition to a career in quantitative vascular biology. This project, addressing the interaction of hemodynamics and vascular biology, is a fundamentally new direction forDr. Quick, yet complements his expertise. Having studied the effect of vascular mechanical properties on oscillatory blood pressure and flow, he can now focus on the effect of oscillatory pressure and flow on vascular mechanical properties. This project represents a natural progression from theoretical tools to study the phenomena of vascular remodeling to the experimental tools to study the mechanisms of remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAPID PATENCY ASSESSMENT OF DIALYSIS VASCULAR ACCESS Principal Investigator & Institution: Mansy, Hansen A.; Biomedical Acoustics Research Company 719 Forest Ave Evanston, Il 60202 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JAN-2005 Summary: (provided by applicant): Vascular access for renal dialysis is a lifeline for about 120,000 patients in the United States. Detection of access compromise is critical for optimal management. The proposed seeks to develop a new method for early and accurate detection of decreased access patency. The essential hypothesis is that vascular compromise alters blood flow turbulence resulting in diagnostic vibration ("acoustic") changes detectable at the skin surface. The proposed technology is based on computerized analysis of signals from "electronic stethoscopes" placed on the patient?s forearm. This is not an imaging technology. Rather, it is a much less expensive, yet potentially powerful method for immediate and safe diagnosis. Phase 1 research will test feasibility by studying fifteen human subjects before and after vascular access angioplasty. If successful, the novel device would have significant commercial potential with purchase by renal dialysis units and radiology departments. A much larger potential market may exist as the knowledge garnered in this effort is later applied to other vascular applications such as stroke prevention, renal artery stenosis detection, femoral-popliteal bypass graft salvage, and to early diagnosis of abdominal aortic aneurysms. PROPOSED COMMERCIAL APPLICATION: If this technology proves successful, it is anticipated that the device would become standard equipment in renal hemodialysis units world-wide with potential estimated sales in the order $30,000,000. Annual sales of disposable sensors are estimated to total an additional $25 million. A much larger potential market may exist as the knowledge garnered in this effort is later applied to other vascular applications such as stroke prevention, renal knowledge garnered in this effort is later applied to other vascular applications such as stroke prevention, renal artery stenosis detection, femoral-popliteal bypass graft salvage, and to early diagnosis of abdominal aortic aneurysms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REACTION AND TRANSPORT DYNAMICS IN HUMAN BLOOD Principal Investigator & Institution: Diamond, Scott L.; Associate Professor; Chemical Engineering; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-JUL-1996; Project End 31-MAR-2005 Summary: (Verbatim from Applicant's Abstract): In the context of a given genotype and phenotype, the dynamics of blood clot assembly ultimately dictate: thrombosis;

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thrombolytic susceptibility of clots; stroke during cardiopulmonary bypass; restenosis after angioplasty; wound healing/inflammation; and pathogenesis of deep vein thrombosis or pulmonary embolism. During blood coagulation, activated platelets and neutrophils from homotypic and heterotypic aggregates through over ten receptormediated pathways while triggering thrombin formation and fibrin polymerization. Yet less is known quantitatively about the strengths and kinetics of platelet-platelet and platelet-neutrophil bonding that leads to aggregation or deposition under coagulating whole blood flow conditions or the biochemical reactivity of these aggregates. Furthermore, temporal resolution of events lasting only a few milliseconds is rarely achieved in most experiments. In vitro high speed imaging experiments will utilize human blood cells and proteins for kinetic studies of these interactions under controlled hemodynamic and coagulation conditions. Probability distributions and kinetic data from these experiments will be used to gain improved mechanistic understanding of human blood phenomena from receptor dynamics to vessel occlusion, in the hemodynamic setting. By defining the molecular dynamics of how blood clots are assembled under flow conditions as well as defining the flow regulation of various clotting scenarios, the risks of unregulated clotting, bleeding, and embolism will be more quantitatively understood for a given disease progression. Specific aims are: Aim 1 High speed imaging of platelet bonding dynamics that regulate thrombosis in clotting blood with emphasis on bond life dynamics. Aim 2 High speed imaging of neutrophil bonding dynamics that enhance cellular deposition with emphasis on selectin mediated pathways, erythrocyte interactions and membrane tethering. Aim 3 Quantifying mechanisms by which neutrophils act as procoagulant participants during clot assembly under defined flow conditions. Aim 4 Develop a set of generalized computational tools for the study of heterotypically aggregating-reacting blood. Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REACTIVE OXYGEN SPECIES REGULATE SMOOTH MUSCLE GROWTH* Principal Investigator & Institution: Nowak, Romana A.; Animal Sciences and Veterinary Pathobiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Uterine leiomyomas, or fibroids, are the most common pelvic tumors in women and are the primary indication for hysterectomy in the US. The incidence of symptomatic leiomyomas is 3-6 times higher in African American women than in other groups. While there may be a genetic component to this increased incidence we believe other factors may play a role. African-Americans show an increased incidence of hypertension, obesity and diabetes. Studies have shown that factors such as angiotensin II, serotonin and oleic acid, which are elevated in the bloodstream of patients with hypertension or obesity, have significant effects on proliferation and matrix production by vascular smooth muscle cells (SMCs) in response to injury. These factors, along with growth factors, regulate growth and differentiation of SMCs via a signaling pathway involving the production of reactive oxygen species (ROS). We hypothesize that similar ROS-dependent mechanisms are involved in the regulation of leiomyoma SMCs. The specific aims of this proposal are: 1. To determine whether ROS are a critical component of the EGF and PDGF signalling pathways in leiomyoma SMCs. 2. To determine whether angiotensin II, serotonin and oleic acid

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Angioplasty

regulate proliferation and extra-cellular matrix production by leiomyoma SMCs and to determine whether these molecules act through their own receptors and/or by transactivating EGF or PDGF receptors. We will also determine the role of ROS in both of these activation pathways. 3. To determine whether halofuginone inhibits growth factor-stimulated proliferation and collagen production by leiomyoma SMCs by either inhibiting the increase in intracellular ROS or one of the downstream targets of ROS. The efficacy of halofuginone in an animal model of leiomyomas will also be assessed. The overall goal of this proposal is to elucidate the role of ROS in the signaling pathways that regulate growth and differentiation of leiomyoma SMCs. Molecules that inhibit ROS production or inhibit downstream targets of ROS may prove to be useful therapeutic agents for the treatment of leiomyomas. Halofuginorle has been shown to inhibit neointimal formation by vascular SMCs in rats undergoing angioplasty and tumor formation in nude mice. We believe halofuginone may act by inhibiting ROSdependent signaling pathways in these cells as well as in leiomyoma SMCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECEPTOR HYPERPLASIA

KINASE

GENE

THERAPY

FOR

NEOINTIMAL

Principal Investigator & Institution: Freedman, Neil J.; Assistant Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 31-MAY-2004 Summary: Percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG) are each used to treat approximately 400,000 coronary artery disease patients annually in the United States. PTCA and saphenous vein grafts in CABG are both complicated by proliferation of smooth muscle cells in the vessel subintima, in a process termed neointimal hyperplasia. Neointimal hyperplasia leads to significant coronary restenosis in approximately 30% of PTCA cases, and engenders significant vein graft stenoses--requiring some sort of intervention--in 30% of CABG cases within two years of surgery. The annual cost of PTCA restenosis alone exceeds $2 billion. This work proposes to test the hypothesis that transient gene therapy with G protein-coupled receptor kinases (GRKs) at the time of PTCA or saphenous in graft placement may substantially alleviate neointimal hyperplasia. GRKs are a family of enzymes which initiate either desensitization or signal termination for many G protein-coupled receptors, several of which have been implicated in the pathology of vascular smooth muscle cell proliferation and restenosis: endothelin A and B, angiotensin II (type I), thrombin, and thromboxane A2 receptors. Over-expression of GRK2 can drastically reduce signaling through all of these receptors in transfected cell systems. Systematically administered antagonists of the endothelin and angiotensin II (type I) receptors significantly reduce neointimal hyperplasia in animal models of vascular injury. This proposal therefore seeks to develop recombinant adenoviruses for expressing GRKs 2, 3, and 5 transiently in smooth muscle cells, and to test each of these recombinant viruses in rabbit and human smooth muscle cells for the ability to reduce cellular responses to agonists for the receptors listed above, as assessed by inositol phosphate signaling, cellular migration, DNA synthesis, and cell proliferation. Subsequently, GRK adenoviruses and adeno-associated viruses will be used ex vivo to treat rabbit jugular veins, which will be grated across the rabbit's ligated carotid artery in a well-established model of neointimal hyperplasia. Four weeks after surgery, vein grafts will be evaluated to determine the GRK's ability (a) to attenuate neointimal hyperplasia in vivo, by histology, and (b) to attenuate agonist-stimulated hyperplasia by

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transiently over-expressed GRKs in the rabbit model of vascular injury would have therapeutic implications for restenosis in PTCA and vein graft failure in CABG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION AND FUNCTION OF MACROPHAGE CD163 Principal Investigator & Institution: Guyre, Paul M.; Professor; Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Recent key observations suggest that CD163 plays an important role in the regulation of inflammation. Expressed only on monocytes (Mo) and macrophages (MO), CD163 was shown last year to be an endocytic scavenger receptor for hemoglobin-haptoglobin (Hb/Hp) complexes. It is notable that haptoglobin has two allelic forms with different affinities for CD163, and haptoglobin phenotype is a predictor of diabetic nephropathy and of restenosis after coronary angioplasty. Moreover, CD163 expression on monocytes is markedly increased by glucocorticoids and IL-10--two mediators that increase rapidly in response to trauma or infection and are well characterized for reducing lipopolysaccharide (LPS) toxicity. Using a newly developed ELISA we show (i) that the extracellular domain of CD163 is rapidly shed from the monocyte after exposure to as little as 50 pg/ml of lipopolysaccharide (LPS) and (ii) that soluble CD163 (sCD163) in plasma rises rapidly and markedly during cardiac surgery with cardiopulmonary bypass, as well as following a bolus injection of LPS into experimental human subjects. A better understanding of the production and function of CD163 is therefore warranted. The goal of this RO3 application is the generation of reagents and pilot data that will enable the PI to establish a new research program focused on understanding the role that CD163 plays in regulating inflammation. The Specific Aims are designed to elucidate the molecular mechanisms of glucocorticoid, cytokine and LPS effects on CD163 expression and shedding. In addition, the newly sequenced murine CD163 will be compared to the human CD163 in terms of synthesis, shedding and Hb/Hp uptake in order to establish an appropriate murine model for future studies. New monoclonal antibodies (mAbs), soluble CD163 fusion proteins, and transfectants expressing both human and murine CD163 will also be developed. Fusion proteins and mAbs will be tested for inhibition of uptake of Hb/Hp complexes via CD163 using primary Mo cultures, Mo cell lines and transfectants. These reagents will also be used in pilot experiments to probe the effect of surface and soluble CD163 on immunological functions. The development of mechanistic and functional information, the generation of human and mouse reagents, and the potential validation of a mouse model should lay the foundation for an expanded application to determine more precisely the role of CD163 in the control of inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXPRESSION

REGULATION

OF

HUMAN

CYTOMEGALOVIRUS

GENE

Principal Investigator & Institution: Stinski, Mark F.; Professor; Microbiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-1976; Project End 31-MAY-2006 Summary: (provided by applicant): Human cytomegalovirus (HCMV) can cause congenital neurological damage and disseminated infections resulting in pneumonitis, retinitis, hepatitis, and gastroenteritis. HCMV infections have been associated with

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accelerated atherosclerosis and with coronary restenosis following angioplasty. HCMV infections in solid organ and bone marrow transplant recipients are a significant cause of morbidity. Both hematopoietic cells of the bone marrow and monocytes of the blood can be latently infected with HCMV. Productive infection occurs in a variety of terminally differentiated cells including fibroblast, cytotrophoblast, smooth muscle, endothelial, epithelial, and mircoglial cells and in macrophages. Abortive infection occurs in polymorphonuclear cells. Our laboratory is interested in viral DNA regulatory elements and in viral and cellular proteins that regulate latency, persistent infection, and productive infection. In Specific Aim I, we propose to determine the role of specific regulatory elements in the proximal 3'-end of the major immediate early (MIE) enhancer on viral gene expression in undifferentiated cells relevant to HCMV latency. Regulatory elements that function to repress transcription from the MIE promoter upon binding a regulator protein in undifferentiated cells of the myeloid lineage will be mutated in the context of the viral genome, and recombinant viruses will be analyzed. In Specific Aim II, we propose to characterize a repressor-boundary region 5' to the MIE enhancer that prevents the MIE enhancer from affecting transcription from the flanking UL1 27 promoter. We have identified a repressor-boundary region between the UL127 promoter and the MIE enhancer that is unique to HCMV and to date, not found in other herpesviruses or DNA viruses. Due to its location, the repressor-boundary region has a role in the temporal expression of the immediate early (IE) and early HCMV genes that flank the MIE enhancer. Downstream of the MIE promoter are the MIE genes, IE1 and 1E2, which encode for proteins of 72 (1E72) and 86 kDa (lE86), respectively. These viral proteins are key regulatory proteins for efficient productive infection. In Specific Aim Ill, we propose to determine early gene regulation in recombinant viruses with both the IEl and IE2 genes deleted and to determine the effects of HCMV tEl and 1E2 gene products on viral and host cell gene expression relevant to the viral life cycle. We will investigate the functions of this replication defective HCMV in activation of viral or cellular gene expression and compare these functions to those of the 1E72 and 1E86 proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF SMOOTH MUSCLE MYOSIN GENE EXPRESSION Principal Investigator & Institution: Owens, Gary K.; Professor and Associate Dean; Mol Physiol/Biological Physics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from Investigator's Abstract): This is a revised application which proposes to study the transcriptional regulation of smooth muscle myosin heavy chain (SM MHC) gene expression. It is expected that through an understanding of the control of transcription of the SM MHC gene which is required in part for the differentiated function of the smooth muscle cell we will learn more about the molecular mechanisms that control the differentiation and/or maturation of smooth muscle cells. Alterations in the differentiated state of smooth muscle cells is thought to play a key role in the development and/or progression of post-angioplasty restenosis and/or atherosclerosis. There are three specific aims as follows: Aim 1 of this proposal will be to identify cellular and molecular mechanisms that regulate cell-type specific expression of the SM MHC gene in vascular SMC in transgenic mice. Aim 2 will be to identify trans acting factors that interact with and regulate the activity of cis elements shown to be important in the SMC-specific regulation of the SM MHC gene identified in aim 1 with a particular emphasis on factors that bind to novel cis regulatory elements of the SM MHC gene or with SM MHC cis elements such as the CArGs that have been shown to be important in

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the regulation of multiple SMC differentiation genes. Aim 3 will be to determine mechanisms responsible for altered expression of SM MHC in SMC within intimal lesions from experimental animal models of vascular injury/post-angioplasty restenosis as well as in human atherosclerotic lesions. The proposed studies represent an extension of the Principal Investigator's ongoing work and will contribute to an understanding of the mechanisms that alter the control of SMC differentiation in atherogenesis and may lead to the identification of possible new interventional therapies. In addition these studies are likely to identify DNA regulatory sequences that confer SMC specific expression that could be used for construction of vectors for SMC specific gene knockouts and/or targeting gene therapies to the vasculature. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF SMOOTH MUSCLE PROLIFERATION Principal Investigator & Institution: Patel, Rekha C.; Biological Sciences; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from Investigator's Abstract): Vascular disease, which is the principal cause of heart attack, stroke and circulatory deficit disorders, is responsible for 50 percent of all mortality in the western world. Proliferation of vascular smooth muscle cells (VSMCs) is a key step in the pathogenesis of atherosclerosis and restenosis after vascular interventions such as angioplasty. Much attention has been focused on the search for an antiproliferative agent to regulate smooth muscle proliferation. Interferons (IFNs), which are cytokines secreted by the immune cells present in the atherosclerotic lesion, have been show to be antiproliferative towards VSMCs. Natural glycosaminoglycans such as heparin are also known to inhibit smooth muscles. Heparin is used widely as one of the local-delivery drugs after invasive procedures. In spite of the well-documented antiproliferative effects of IFNs and heparin on VSMCs, the molecular mechanisms that are involved have not yet been identified. PKR (protein kinase, RNA activated) is an IFN induced, growth inhibitory protein kinase, which is activated by double stranded (ds) RNA in virus-infected cells. PKR's role in regulation of cell proliferation has become clear in recent years. It's over expression or activation has been shown to be growth inhibitory. PKR is also activated by heparin in vitro and our results indicate that treatment of VSMCs with heparin results in activation of PKR. PKR is also induced at the transcriptional level by IFN treatment of VSMCs We hypothesize that, PKR is involved in mediation both heparin and IFN's antiproliferative effect towards VSMCs. We propose to test this with the following specific aims: 1. To investigate the role of PKR in the antiproliferative action of heparin and IFN on VSMCs. 2. To characterize the functional domains of PKR involved in mediating heparin's antiproliferative effect. The long-term goal of this proposal is to elucidate the molecular mechanisms involved in the inhibition of VSMC grown by heparin and IFN thereby offering on opportunity to design better ways of controlling the vascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF VESSEL WALL APOPTOSIS Principal Investigator & Institution: Walsh, Kenneth; Assoicate Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from Investigator's Abstract): Vascular injury has been shown to induce proliferation and apoptosis in vascular smooth muscle cells (VSMCs), and this

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balance between cell growth and cell death will ultimately influence the size of the injury-induced lesion. Apoptotic cell death has been documented in human atherectomy and endarterectomy specimens and in a number of animal models of vessel wall stenosis. Recently, they have shown that as early as 30 minutes following balloon injury VSMCs of rat carotid and rabbit iliac arteries undergo apoptotic cell death at a high frequency as demonstrated by TUNEL staining, and by the appearance of condensed chromatin and other morphological features characteristic of apoptosis in electron micrographs. This induction of apoptosis coincides with a marked downregulation of the bcl-X protein, a potential cell death antagonist. Their data suggest that VSMC apoptosis is a rapid and prominent cellular response to acute vascular wall injury, the extent of this apoptotic response may ultimately influence characteristics of the lesion that result from the insult. To more fully understand the regulation and the role of apoptosis in vessel wall lesion formation, it is proposed to: 1) determine the frequencies of VSMC apoptosis in single injury and double-injury model of angioplasty in rabbit external iliac arteries; 2) assess the effects of enhanced apoptosis on vessel lesion formation using a replication defective adenovirus encoding Fas ligand; 3) characterize apoptosis in a mouse model of arterial injury; and 4) study the mechanisms that coordinate cell cycle and apoptosis at a molecular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATON OF CELL PROLIFERATION Principal Investigator & Institution: Kelm, Robert J.; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 01-AUG-1995; Project End 31-JUL-2007 Summary: (provided by applicant): Neoinitimal hyperplasia is a common complicating feature of atherosclerosis, restenosis after angioplasty, and transplant vasculopathy. At the cell level, over-growth of the arterial wall is triggered by inflammatory signals that promote progressive phenotypic changes resulting in enhanced cell proliferation and migration. Evidence suggests that this dedifferentiation process known as phenotypic modulation may occur in both medial smooth muscle cells and adventitial fibroblasts where the biochemical hallmark of cell reprogramming is alteration in expression of vascular smooth muscle (VSM) alpha-actin, a cytoskeletal protein important for regulation of vascular contraction and cell movement. Hence, elucidation of the mechanisms governing expression of the VSM alpha-actin gene in cells of myogenic and fibroblastic lineage may reveal molecular targets of clinical utility in the management of atherosclerotic plaque stability and/or restenosis after surgical intervention. The primary goal of this research is to define the gene regulatory function(s) of a novel group of single-stranded DNA and mRNA-binding factors known as Puralpha, Purbeta, and MSYI. These proteins have been implicated in coordinately suppressing VSM alphaactin gene expression in myofibroblasts and smooth muscle cells by both transcriptional and post-transcriptional mechanisms. In this proposal, particular emphasis will be placed on the participation of Purbeta in these processes since this protein appears to be the key component required for repression of the VSM alpha-actin promoter in cultured cells and because its pattern of expression in vascular tissue specimens is consistent with a role in phenotypic modulation. In vitro and in vivo approaches will be used to test predictions arising from conceptual models of gene regulation by 1) mapping structural domains and chemical modifications required for interaction of Purbeta with relevant nucleic acid and protein-binding partners 2) analyzing the assembly and disassembly of Pur-containing regulatory complexes on the genomic VSM alpha-actin promoter, 3) evaluating the ability of Pur and Y-box proteins to inhibit translation of VSM alpha-actin

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mRNA, and 4) characterizing the time-course of expression of Puralpha, Purbeta, and MSY1 in mouse models of vascular disease and injury. This research will contribute to an improved understanding of a unique class of single-stranded nucleic acid-binding factors that may account for the remarkable plasticity of VSM alpha-actin expression and phenotypic modulation during vascular remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESTENOSIS AND ENDOTHELIAL PROLIFERATION Principal Investigator & Institution: Losordo, Douglas W.; Chief, Cardiovascular Research; St. Elizabeth's Medical Center of Boston 736 Cambridge St Boston, Ma 02135 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: (Adapted from Investigator's Abstract): The overall goal of this research is to inhibit arterial restenosis by promoting better re-endothelialization of an arterial segment after angioplasty. The authors have obtained evidence that TNF is expressed at sites of balloon injury in vivo, and can inhibit endothelial proliferation in vitro. This TNF inhibition appears to work via a repression of the cell cycle regulatory factors E2F1 and cyclin A. They hypothesize that the in vivo expression of TNF is a major factor leading to delayed endothelial regrowth in the injured artery, and thereby promoting intimal thickening as a major part of the restenosis process. By extension, they have preliminary data indicating that E2F1 over expression in the artery wall can accelerate re-endothelialization and thereby inhibit restenosis. The resultant specific aims are therefore as follows: Investigate the role of E2F1 in re-endothelialization and restenosis after balloon angioplasty. They propose to characterize the effect of local overexpression of E2F1 (using adenoviral delivery) on re-endothelialization in the rat carotid injury model. These studies will then be complemented by an analysis of a newly developed mouse carotid artery injury model, using the E2F1 deficient mouse; both in the absence of E2F1, and after adding back E2F1 via adenoviral gene transfer. Investigate certain mechanisms involved in the inhibition of endothelial cell proliferation after balloon angioplasty. Here they plan to determine the molecular mechanisms relevant to TNF-induced inhibition of endothelial proliferation via the repression of E2F1 mRNA and protein expression, with the subsequent down regulation of cyclin A activity. Thus, with respect to the E2F1 gene, they will identify the cis-acting DNA sequences that regulate TNF mediated changes in E2F1 expression in endothelial cells, and characterize the trans-acting factors that bind to these elements. They will also determine the cis elements responsible for TNF-induced repression of cyclin A gene expression and similarly identify relevant trans-acting factors binding to these elements. Investigate the role of cyclin A in restoring proliferation of endothelial cells exposed to TNF. Additional data indicate that cyclin A over-expression alone is sufficient to overcome TNF-mediated endothelial cell growth arrest. They will therefore determine if cyclin A is capable of exerting independent proliferation and survival effects on TNF exposed endothelial cells by over-expressing cyclin A using a tetracycline-responsive inducible gene expression system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTINS ROLE IN VASCULAR INJURY IN GENE-TARGETED MICE Principal Investigator & Institution: Sarembock, Ian J.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005

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Summary: Restenosis after percutaneous interventions remain a major challenge, occurring in 20-40 percent after balloon angioplasty or stents. Neointima formation is an important mechanism and represents a complex healing process that includes adhesive interactions between inflammatory cells and the vessel wall. The selectin adhesion molecules participate in the early steps of leukocyte recruitment but their exact role after vascular injury is incompletely understood. Accordingly, the primary goal of this proposal is to understand the role of E- and P-selectin and their interactions on neutrophil and macrophage/foam cell accumulation and neointimal growth following arterial injury using gene-targeted mice deficient in expression of apoE plus P-selectin and/or E-selectin and monoclonal antibodies directed against E- and/or P-selectin. SpecificAim1 will test the hypothesis that elimination of P-selectin and/or E-selectin by gene-targeting limits leukocyte entry and accumulation and neointima formation following carotid denudation injury in apoE deficient mice. Histomorphometry and detailed immunohistochemical analysis will be utilized together with serial MRI imaging. Although P-selectin has recently been shown to occupy a preeminent role in regulating leukocyte behavior in a mouse model of inflammation, both discrete functional differences and similar/overlapping functions are described for E- and Pselectin. Accordingly, Specific Aim 2 will test the hypothesis that transient inhibition of E-selectin, P-selectin or both using blocking monoclonal antibodies each or together limit leukocyte entry and accumulation and neointima formation following carotid denudation injury in gene-targeted mice deficient in expression of apoE. To address the specific mechanism(s) by which P-selectin is anticipated to exert its protective effect on vascular repair after wire denudation injury, bone marrow transplantation will be performed in aim 3. Specific Aim 3 will test the hypothesis that platelet P-selectin is responsible for the protective effect of P-selectin deletion/blockade on leukocyte accumulation and neointima formation following carotid denudation injury in genetargeted mice deficient in expression of apoE. Taken together, these studies will provide new insights into the role(s) of the selectins in inflammatory cell trafficking and neointimal growth after vascular injury in atherosclerosis-prone apoE-deficient mice. In addition, these studies will open new avenues to potential therapeutic strategies to limit neointimal growth after vascular injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL TRANSDUCTION OF SMOOTH MUSCLE Principal Investigator & Institution: Somlyo, Avril V.; Professor; Mol Physiol/Biological Physics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JAN-1977; Project End 31-DEC-2004 Summary: This multi-disciplinary program will elucidate the signal transduction pathways that regulate vascular smooth muscle development, hypertrophy, gene expression and contraction-processes that are subject to abnormalities contributing to high blood pressure, atherosclerosis, vasospasm, post-angioplasty restenosis and shock. The Projects are mutually interdependent, converge on investigation of a common theme of understanding smooth muscle cell contraction and growth, and require the complementary expertise available in molecular biology (Project 3), biochemistry (Project 2), physiology (Project 1) and biophysics and generation of novel probes (Core A). Newly developed tools and methods will be utilized for identifying and characterizing protein kinases and phosphatases, their upstream and downstream targets, and crossbridge- state kinetics. New reagents and methods include gammaphosphate- activated ATP for affinity purification of protein kinases, mixed peptide sequencing of fmol level proteins, environmentally sensitive fluorescent nucleotide

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analogous, caged nucleotides, peptides and fatty acids, techniques for measuring contractility of embryonic smooth muscle, and the exchange of myosin light chains in situ. Project 1 and Core A will measure the kinetics of product release from myosin and test the hypothesis that a combination of variable expression of essential light chain and myosin and test the hypothesis that a combination of variable expression of essential light chain and myosin heavy chain isoforms determines the variable affinity of smooth muscles for MgADP and crossbridge kinetics. Project 2 and Core A will identify protein kinases and phosphatases that regulate smooth muscle myosin sequencing. In conjunction with the functional methods of Project 1, Project 3 will use these methods to identify kinases, phosphatases and their transcriptional targets that regulate angiotensin-induced smooth muscle hypertrophy, also testing the hypothesis that angiotensin-II plays an important role in control of smooth muscle cell differentiation and maturation during vascular development and mediates adaptive changes in contractile mass of SMC in adult animals. The effects of knockout of angiotensinogen, the angiotensin AT2 or AT1 receptors and MHox on SMC investment and/or growth differentiation/maturation during development will be determined in Project 2. The physiological role of telokin, a putative smooth muscle myosin phosphate activator, will be evaluated in transgenic and knockout animals (Projects 1, 2 and 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUBSTRATE SPECIFICITY OF HUMAN FIBRINOLYTIC PROTEASES Principal Investigator & Institution: Madison, Edwin L.; Associate Professor; Torrey Pines Institute/Molecular Studies Molecular Studies San Diego, Ca 92121 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-JUL-2004 Summary: Five broad, long term goals of this laboratory are (i) to increase understanding of the molecular determinants of substrate specificity of (chymo) trypsinlike serine proteases, a large gene family that includes many medically important members and is among the most advanced model systems of enzymology, (ii) to develop powerful and robust techniques to distinguish the specificities of very closely related proteases, (iii) to facilitate the rational design of highly specific inhibitors of individual proteases, which can be used to examine the role of a particular protease in complex biological or pathological processes, (iv) to aid the de novo design of novel proteases with desired substrate specificities, and (v) to assist the development of novel therapeutic agents for the treatment of acute myocardial infarction and other thromboembolic disorders. The specific aims of this renewal application are: 1 ) To elucidate optimal subsite occupancy for substrates of all three proteases of the human fibrinolytic cascade, tissue type plasminogen activator (t-PA), urokinase (u-PA), and plasmin, using both conventional and novel substrate phage display protocols. 2) To use site specific mutagenesis to identify and characterize molecular determinants of the stringent substrate specificities of t-PA and u-PA. 3) To design and characterize high affinity, specific inhibitors of u- PA. The proposed studies are interdisciplinary and involve the use of techniques of molecular biology (e.g., site directed mutagenesis, phage display), biochemistry (enzyme expression and purification, enzyme and inhibitor kinetics), biophysics (molecular modeling, X-ray crystallography), and chemistry (synthesis and characterization of small peptide substrates and peptidic inhibitors of serine proteases). The primary objective of this proposal, to increase understanding of the activity, specificity, and selective inhibition of fibrinolytic serine proteases, ensures that these studies will be directly relevant to human health. Administration of one of these enzymes (t-PA) is currently the standard treatment for acute myocardial infarction, the major killer of both American men and women. The

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development of novel plasminogen activators with altered or new properties, therefore, may provide improved thrombolytic agents. In addition, the development of high affinity, highly selective inhibitors of u-PA may provide new therapeutic tools to combat restenosis following invasive vascular procedures such as angioplasty. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETING G PROTEINS IN VASCULAR INTIMAL HYPERPLASIA Principal Investigator & Institution: Koch, Walter J,.; W.W. Smith Professor of Cardiology; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: Major clinical problems caused by unchecked vascular smooth muscle (VSM) proliferation and migration (intimal hyperplasia) can occur following surgical by-pass leading to vein-graft failure or restenosis following arterial angioplasty. Several agents present in serum have been shown to stimulate mitogenesis via dissociated heterotrimeric G proteins (Gq and Gi) appear to be critically involved in the pathological process of intimal hyperplasia since several serum mitogens, such as angiotensin II and thrombin, can activate cellular receptors that can couple to Gq and/or Gi. Peptide inhibitors targeted specifically against Galphaq (GqI) and Gbetagamma (BetaARKct) signaling have recently been developed and thus, molecular inhibitors of Galphaq and Gbetagamma-mediated signaling may represent a novel therapeutic approach to limit vein-graft failure and arterial restenosis after angioplasty. The Overall Hypothesis of this proposal is that G proteins are a critical regulator of VSM cellular proliferation and migration, especially in injured vessels. Furthermore, the targeted inhibition of intracellular G protein signaling, including Gbetagamma inhibition, will lead to a broader understanding of the molecular mechanisms involved in these processes, which may lead to novel molecular therapies to limit the pathological process of intimal hyperplasia. Several in vitro and in vivo model systems are available to test this hypothesis including a rabbit vein-graft model and a porcine coronary artery angioplasty and stent restenosis model. To delivery the GqI and betaArkct peptides to VSM cells in culture and in vivo to the vascular wall, we will utilize adenoviral vectors. The associated Specific Aims are: (1) To identify the specific role of Galphaq and Gbetagamma in the activation of cellular migration and proliferation in VSM cells using in vitro model systems; (2) To determine if in vivo inhibition of Galphaq or Gbetagamma signaling in VSM via adenoviral-mediated gene transfer will limit intimal hyperplasia during vein-graft failure; (3) To determine if adenoviral-mediated delivery of the GqI and betaArkct transgenes to the arterial wall will prevent restenosis is clinically relevant animal models; (4) To evaluate gene transfer to VSM cells within the vessel wall using "advanced" adenovirus and AAV vectors in attempts to more efficiently deliver the peptide inhibitors of Galphaq and Gbetagamma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THROMBIN-PAR-1 SIGNALING IN CARDIAC I/R INJURY Principal Investigator & Institution: Mackman, Nigel; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Myocardial I/R injury is a significant clinical problem and contributes to loss of myocardial tissue after restoration of blood flow after angioplasty, after administration of thrombolytics and following coronary artery bypass surgery. The broad, long-term goal of this proposal is to understand how thrombin

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contributes to inflammation during myocardial ischemia-reperfusion (I/R) injury. Our preliminary data suggest that I/R injury induces endothelial cell damage and leakage of clotting factors into the myocardium. Cardiomyocyte tissue factor initiates the clotting cascade and generates the coagulation protease thrombin. We hypothesize that thrombin cleavage of PAR-1 on endothelial cells increases the expression of proinflammatory mediators, such as KC and MCP-1, and recruitment of PMNs. The proposal contains three specific aims. Specific Aim 1 will determine the role of PAR-1 in myocardial I/R injury. Specific Aim 2 will determine the expression pattern of Egr-l and its role in myocardial L/R injury. Specific Aim 3 will identify thrombin-PAR-1dependent inflammatory genes in myocardial I/R injury. Our studies should increase the fundamental knowledge of the role of the thrombin-PAR-1 signaling pathway in myocardial I/R injury and may lead to the development of novel therapies to preserve ischemic myocardium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THROMBOPROPHYLAXIS IN THE SURGICAL SETTING Principal Investigator & Institution: Muzykantov, Vladimir R.; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Verbatim from Investigator's Abstract): Thrombosis is a common complication of surgery that increases perioperative morbidity and mortality. For thromboprophylaxis to be practical in the perioperative setting, an approach must sustain physiologic fibrin formation to avoid perioperative bleeding and permit wound repair, while at the same time prevent pathological thrombi from forming. The investigators postulate that coupling plasminogen activators (PA's) to carrier red blood cells (RBC) will deny the enzymes ready access to mature clots or to extravascular fibrin, but will prolong their life-span within the circulation and permit them to be incorporated within newly formed clots. The preliminary results support this hypothesis and show that PAs can be coupled to RBC without loss of biocompatibility, circulate for a prolonged time and display selective fibrinolytic activity against newly formed clots in vitro and likely in vivo. The investigators have also observed that: (1) single chain urokinase (scuPA) bound to its soluble receptor (suPAR) is enzymatically active, fibrin specific, resistant to plasminogen activator inhibitor-1 (PAI-1), but its activity is regulated by the fourth kringle of plasminogen (K4); (2) a scuPA variant lacking the kringle (DK-scuPA) displays enhanced enzymatic activity, is relatively resistant to PAI-1. Retains high affinity binding to suPAR, and acquires antivasoconstrictor activity; (3) suPAR can be coupled to circulating RBC via complement receptor-1 (CR-1) allowing scuPA to bind to circulating RBC without ex vivo manipulation. The investigators hypothesize that coupling scuPA or DK-scuPA to RBC via suPAR will generate a latent pro-drug which has little, if any, access to mature clots, but which enjoys a prolonged life-span and ready access to nascent clots which induce its activity. Based on these findings, the investigators propose to study the behavior of RBC-coupled scuPA and DK-scuPA and efficacy and safety in animal models that recapitulate common post surgical thrombotic situations. The following specific aims will be pursued: (1) Biologic activity of uPA coupled to RBC (uPA/RBC). The stability, enzymatic and vasoregulatory activity, resistance to PAI-1, adhesivity and regulation by plasminogen of uPA/RBC will be investigated in vitro. (2) Bioavailability of UPA/RBC in vivo. The investigators will characterize the stability, blood clearance, biodistribution, and activities of uPA/RBC injected into intact animals. (3) Efficacy of uPA/RBC in animal mdels of thromboembolism. Animal models of pulmonary and cerebral

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embolism that have been developed in the investigators' laboratory will be employed to study uPA/RBC-mediated thromboprophylaxis in intact rodents and in genetically altered mice. The results of this study may provide new means to achieve thromboprophylaxis in surgical settings such as angioplasty and endarterectomy, as well as be a platform for the development of novel forms of antithrombotic therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TISSUE FACTOR, THROMBOSIS AND THE ARTERIAL WALL Principal Investigator & Institution: Nemerson, Yale R.; Professor of Medicine; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 31-JAN-2006 Summary: This is a competitive renewal of a SCOR in Hemostatic and Thrombotic Diseases by a highly-interactive group of investigators at the Mount Sinai School of Medicine. The program is comparised of 5 projects and 3 cores. Findings by the SCOR investigators and other laboratories have established the presence of circulating tissue factor (TF). Our program, in particular has demonstrated that this TF is active and can initiate thrombus formation. The project of Dr. Fuster will measure circulating TF in patients with risk factors for atherosclerosis and thrombosis and will examine the effect of risk factor reduction on TF levels and thrombogenicity. Dr. Fuster has found collaborations with investigators that will provide samples from several important clinical studies. Dr. Nemerson's project will explore the novel finding that leukocytes can transfer TF to the surface of platelets and will attempt to identify the platelet "TF receptor." Based on the finding that large thrombi stain diffusely the TF, Dr. Nemerson will develop mathematical models to examine the diffusion of molecules within the thrombus. Dr. Taubman's project will study the role of smooth muscle cells (SMC) and cardiomyocytes in releasing TF into the microcirculation after angioplasty and myocardial infarction. He will employ pig models of coronary artery injury and infarction and novel transgenic mice in which TF is conditionally knocked out in SMC and cardiomyocytes to examine the role of TF in mediating infarct size and intimal hyperplasia. These closely- linked projects promise to establish new paradigms for TF generation and biology. A second major focus of the SCOR is on platelet-leukocyte interactions. The project of Dr. Harpel will examine the role of I-309, a CC-chemokine, in regulating leukocyte accumulation in arterial injury. His findings that platelets possess I-309 has led to the novel hypothesis that the release of I-309 by platelets accumulating at the site of injury is critical to the early recruitment of leukocytes. He will also examine the role of I-309 in mediating endothelial cell migration and vasculogenesis. Dr. Coller's project will undertake a detailed examination of the interaction between leukocytes and platelets in regulating arterial thrombosis and leukocyte transmigration. His project involves several recently-developed models of thrombosis and novel transgenic animals. In support of this project will be a Pathology Core, a Thrombosis Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRAFFICKING OF ADENOVIRUS VECTORS IN ENDOTHELIAL CELLS Principal Investigator & Institution: Leopold, Philip L.; Assistant Professor; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): The anatomic location of the endothelial cell makes it an ideal target for in vivo gene transfer with consequent genetic modification of the endothelial cell for a variety of therapeutic purposes, including induction of angiogenesis, prevention of restenosis, following angioplasty, suppression of vessel growth in tumors, and as a source of therapeutic proteins for treatment of hereditary and acquired disorders. Of all gene transfer vectors available, adenovirus has been most effective at mediating endothelial gene transfer, but high vector concentrations are necessary, with the attendant risks for adverse events related to the vector. In this context, strategies using adenovirus vectors to transfer genes to endothelial cells could benefit from improved efficiency of gene transfer to endothelial cells which would lead to a corresponding decrease in dose of vector delivered to the patient. To realize the potential for increasing gene transfer to endothelial cells, the biology of gene transfer to endothelial cells must first by characterized. In this context, the central hypothesis of this proposal is that the evaluation of adenovirus trafficking in endothelial cells will yield strategies for improved efficiency of gene transfer to endothelial cells. To pursue this hypothesis, adenovirus interaction with endothelial cells will be evaluated in the context of varying physiological states of endothelial cells including resting or activated endothelial cells, as sub-confluent cultures, confluent polarized monolayers, or wounded polarized monolayers. These strategies will lay a foundation for understanding the impact of altered adenovirus tropism on efficiency of gene transfer to endothelial cells. This project is focused on two aims: (1) To characterize efficiency of adenovirus binding and intracellular trafficking in varying physiological states of endothelial cells; and (2) To characterize adenovirus entry and trafficking in endothelial cells subsequent to infection via alternate cell surface receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TYROSINE KINASES IN G PROTEIN MEDIATED SIGNALING Principal Investigator & Institution: Luttrell, Louis M.; Associate Professor of Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 25-SEP-1998; Project End 31-AUG-2003 Summary: (Applicant's Abstract): Our current understanding of the processes which regulate cellular mitogenesis is derived largely from the study of receptor tyrosine kinases, transforming viral oncogenes, and their normal cellular homologues. Recently, receptors which couple to heterotrimeric G proteins have also been shown to mediate signals which regulate cellular growth and differentiation. Growing evidence suggests that these receptors, which mediate potent mitogenic responses to a variety of humoral, endothelium- or platelet-derived substances, participate in the regulation of cellular proliferation in both physiologic and pathophysiologic states and in cellular transformation in some, mostly neuroendocrine, tumors. Perhaps surprisingly, many of these G protein-coupled receptor-derived signals are dependent upon the regulation of tyrosine protein kinases, and are thus indicative of complex crosstalk between G protein-coupled receptor and receptor tyrosine kinase signaling cascades. To date, four distinct classes of tyrosine protein kinase; src kinases, focal adhesion kinases (FAK), receptor tyrosine kinases, and Janus kinases, have been implicated in various aspects of G protein-coupled receptor signaling. The molecular mechanisms whereby these kinases are regulated, and their roles in transduction of G protein-coupled receptor-mediated mitogenic signals, is largely unknown. This project tests the hypothesis that G proteincoupled receptors mediate signals which regulate gene expression, and control cytoskeletal rearrangement, via the activation and targeting of tyrosine kinases to specific multi-protein signaling complexes. Employing Gs-, Gi, and Gq/11-coupling

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receptors in cultured cell model systems as well as primary cultures of cardiac and vascular smooth muscle, the first specific aim of the project is to determine the proximal mechanisms whereby G protein-coupled receptors regulate the activity of src, FAK and receptor tyrosine kinases. A parallel aim is to determine the role of activated csrc/receptor tyrosine kinase, and c-src/FAK complexes in the regulation of mitogenactivated protein kinase cascades. Another aim is to determine the role of these kinase complexes in mediating G protein-coupled receptor-dependent reorganization of the actin cytoskeleton. Understanding the mechanisms whereby G protein-coupled receptors regulate these components of the mitogenic signal may facilitate the identification of targets for the prevention of the proliferative complications of conditions such as diabetes mellitus, atherosclerosis and post-angioplasty restenosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ULTRASOUND MEDIATED PERMEABILITY-DRUG DELIVERY Principal Investigator & Institution: Hansmann, Douglas R.; Ekos Corporation 22122 20Th Ave Se, Ste 148 Bothell, Wa 98021 Timing: Fiscal Year 2002; Project Start 15-JAN-1999; Project End 31-JAN-2005 Summary: (Verbatim from Applicant's Abstract): The goal of this project is to demonstrate the feasibility of using ultrasound to temporarily make vascular tissue and cell membranes more permeable to deliver drug to vessel walls. EKOS has developed an ultrasound-catheter device for transmural drug delivery that may be useful in the treatment of restenosis following balloon angioplasty. Local ultrasound enhanced drug delivery may increase the usefulness of drugs that are too toxic or expensive to deliver systemically. The results of Phase I demonstrated that ultrasound can make eukaryotic cells permeable for the uptake of exogenous materials. The permeability was correlated with aspects of the acoustic signature radiated by the cavitation field in the cell suspension during exposure. The aims of Phase II are to determine the effect of acoustic parameters on molecular uptake and cell viability in simple cell suspensions and more complex organized tissues and to develop a measure for the cavitation mediated permeability based on acoustic signature analysis. This measure will give a real time feedback predicting the bioeffects for optimizing therapy delivery. PROPOSED COMMERCIAL APPLICATION: The EKOS product will be an ultrasound catheter device that actively delivers drug into the artery wall for the treatment of restenosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UROKINASE KRINGLE-MEDIATED VASCULAR REMODELING Principal Investigator & Institution: Cines, Douglas B.; Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: Urokinase plasminogen activator (uPA) has been implicated in fibrinolysis and diverse processes that involve cell migration such as atherosclerosis, angiogenesis, wound repair, and tumor metastases. Studies in mice with targeted deletion of the genes for uPA and uPAR indicate that uPA induces transmembrane signaling through pathways discrete from those involved in binding to its glycolipid-anchored receptor (uPAR), but to date the details of this mechanism have not been elucidated. uPA is composed of a receptor-binding growth factor domain, a kringle domain, the function of which is unknown, and a protease domain. Recent studies from our laboratories demonstrate that the kringle of uPA binds to vascular smooth muscle cells (VSMC) and delivers a signal that potentiates uPA-mediated VSMC contraction and cell migration.

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Further, recognition of the kringle mediates clearance of uPA from cell surfaces, suggesting the kringle domain represents an important control point in VSMC function. We now propose to extend these studies and to examine these newly described properties of the uPA kringle in greater detail through five inter-related specific aims. 1) We will characterize the interaction of the uPA kringle with the low-density lipoprotein receptor/alpha2 macroglobulin receptor which mediates uPA degradation. 2) We will isolate and identify the uPA-kringle binding protein on VSMC. 3) We will examine the kringle-mediated signal transduction pathway in VSMC. 4) We will study the interaction between kringle binding protein-dependent and uPAR-dependent signal transduction events in VSMC using uPA variants capable of activation either or both pathways. 5) We will examine the role of the uPA kringle and kringle binding protein in vascular wall remodeling in a rat model of intravascular trauma. These studies will provide insight into a newly described uPA-mediated signal transduction pathway involved in smooth muscle cell migration and vascular repair. Identification of the kringle binding protein may provide an opportunity to modulate the contribution of vascular smooth muscle cell proliferation and migration to atherosclerosis and restenosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: USE OF TEG TO MONITOR GPIIB/IIIA AT THE BEDSIDE Principal Investigator & Institution: Cohen, Eli; Haemoscope Corporation 7855 Gross Point Rd, #g-4 Skokie, Il 60077 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: Phase I results show that the modified Thrombelastograph(R) Coagulation Analyzer (TEG(R)) assay to monitor platelet glycoprotein Ilb/IIIa (GPIIb/IIla) receptor blockade in patients being treated with c7E3 Fab provides an equivalent or better assessment of platelet GPIIb/IIla receptor blockade than the "gold standard" turbidimetric platelet aggregation test. Furthermore, in Phase I an individualized dosing algorithm with the use of the TEG(R) assay was developed. Using this algorithm, Phase II patients undergoing PTCA treated with c7E3 Fab can be individually dosed to achieve 80% reduction in Gp due to platelet inhibition. Further, Phase II will validate and expand the new test by: *Increasing the sample size to 400 to enhance the validity of the study, and increasing the participating hospitals to two, using institutions with a more diverse patient population. * Extending the Phase I study to encompass an additional GPIIb/IlIa inhibitor, eptibatide (Integrilin(TM)), to generalize the TEG(R) assessment of platelet GPIIb/IIla blockade. * Evaluating and refining the Phase I individualized dosing and comparing its clinical utility with the standard protocol of a weight-adjusted treatment of platelet blocker drugs to demonstrate reduced bleeding complications and decreased ischemic events and death. PROPOSED COMMERCIAL APPLICATIONS: The TEG(R) assay will be commercialized and used as a dedicated kit to monitor, assess and individualize dosing of GPIIb/IIia blockade in individuals being treated with c7E3 Fab, Integrilin or other new platelet inhibitor drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VASCULAR GENE TRANSFER USING A NOVEL CELLULAR STENT Principal Investigator & Institution: Caplice, Noel M.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003

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Summary: Chronic total occlusion (CTO) of the coronary artery represents between 1020% of all cases of coronary artery disease, the leading cause of death in the developed world. CTOs are currently inadequately treated and it has proven very difficult to improve distal vessel perfusion in this setting with conventional revascularization strategies such as angioplasty or stenting. One approach which may improve distal vessel perfusion in CTO patients is therapeutic angiogenesis. We have recently developed a novel "felt-stent" consisting of a felt-like stainless steel mesh backbone on a conventional stent which can incorporate seeded vascular smooth muscle cells. These cells can be genetically altered and reimplanted on a stent platform in the vasculature. Our central hypothesis is that targeted cell based gene delivery using a regulated retroviral VEGF vector will induce functional and sustained angiogenesis. This will be examined using the felt stent platform in a porcine model of CTO. The overall goal of this proposal is to provide better options for VEGF gene transfer in the vasculature. This will be achieved through use of a novel felt-stent as a platform for regionally targeted cell-based VEGF gene transfer in vivo. The specific objectives of the proposal will be to establish VEGF gene transfer which is durable, temporally regulated efficient, safe and ultimately therapeutic for angiogenesis in the setting of CTO. The specific aims are as follows: 1. To optimize cell based retroviral VEGF gene transfer using a felt-stent in the normal porcine coronary artery. 2. To determine, using the same in vivo stent delivery, the feasibility of long-term temporal control of VEGF gene transfer using a rapamycin transcription regulation system. 3. To determine the therapeutic efficacy of this combined delivery and regulated VEGF vector system for induction of angiogenesis in a porcine models of CTO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR ANGIOPLASTY

TONE

&

CAMP

PHOSPHODIESTERASE

IN

Principal Investigator & Institution: Smith, Carolyn J.; Associate Professor; Pathology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by the applicant): Enhanced smooth muscle cell (SMC) proliferation and migration account for intimal thickening, which follows balloon catheter de-endothelialization (BAL) of rat aorta. Recent studies show activation of cAMP-dependent protein kinase (PKA) by specific inhibition of cAMP phosphodiesterases PDE3 and/or PDE4 reduces SMC proliferation/ migration and lesions after angioplasty. In addition to changes in SMC growth, contractility may be affected by injury. Overall hypothesis: BAL leads to enhanced expression and activity of specific cAMP PDEs in both SMC and vessel wall-associated inflammatory cells, which then affects SMC cyclic nucleotide levels, protein phosphorylation and contractility. The project will first identify which high affinity, cAMP-selective PDE3 and PDE4 isoforms are upregulated in the BAL-injured rat aorta or growth factor-stimulated rat aortic SMC, while later aims assess the impact of PDE upregulation on cAMP-dependent phosphorylation, vessel contractility, and cellular locale. Aim 1A: Determine the time course of protein expression for PDE3A/3B and PDE4A/4B/4D genes following BAL in vivo. Pilot data for aortic medial SMC, show, that BAL is associated with biphasic increases in PDE4B mRNA, and smaller (PDE3B) or, no changes in other genes (PDE3A, 4D). Aim lB: To determine the time course of PDE4B, PDE4D and PDE3A protein splice variants in RASMC stimulated with serum, PDGF-BB or bFGF. Aim 2A: Determine the time course for PDE inhibitor enhancement of PKA activity, or PKA-dependent phosphorylation of a vasodilator-sensitive substrate VASP in SMC. These indices of

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intracellular cAMP will be used to determine if inhibition of overexpressed PDE3/4 in BAL restores or enhances beta-agonist and forskolin-dependent activation. Aim 2B: Determine the impact of PDE3/4 upregulation in vitro on VASP phosphorylation and PKA activity. Aim 3: Characterize contractility of the BAL aorta at 24 hr and 1-2 weeks after injury with various vasodilators plus/minus PDE inhibitors. Aim 4: Identify at 24 hr and 7-14 days after BAL the aortic cellular specificity of PDE expression by immunohistochemistry and in situ hybridization. The increase in PDE3/4 is predicted to reduce vasorelaxation produced by agents, which increase cAMP and cGMP levels. PDE overexpression favors vasospasm, which may affect vessel wall remodeling. Upregulation of specific PDEs represents an important response to injury that may serve as a therapeutic target in restenosis and hypertension Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WARFARIN VS ASPIRIN FOR INTRACRANIAL ARTERIAL STENOSIS Principal Investigator & Institution: Chimowitz, Marc I.; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 25-SEP-1998; Project End 31-JUL-2003 Summary: Background and Relevance. Atherosclerotic stenosis of the major intracranial arteries causes 40,000 strokes per year in the USA, costing the country at least 600,000,000 dollars annually. There have been no prospective trials evaluating optimal medical therapy for this disease. The main objective of this clinical trial is to compare warfarin (INR 2-3) with aspirin (1300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients with symptomatic stenosis of a major intracranial artery. Study Design. Prospective, randomized, double-blind, multi-center trial. The sample size required will be 403 patients per group (based on stroke and vascular death rates of 33 percent/3 years in the aspirin group vs 22 percent/3 years in the warfarin group, an alpha of 0.05, beta of 0.80, a 24 percent withdrawal of therapy rate, and a 1 percent drop out rate). Conduct of Trial. Patients with transient ischemic attack (TIA) or stroke caused by angiographically proven stenosis (greater than or equal to 50 percent) of a major intracranial artery will be randomized to warfarin or aspirin. The dose of warfarin will be adjusted to maintain the INR between 2-3 based on monthly blood tests. Patients will be contacted monthly by phone and examined every four months (mean follow-up of 3 years) to determine whether any endpoints have occurred. The primary analysis will compare the rates of stroke (ischemic and hemorrhagic) and vascular death in the two treatment groups. Secondary analyses will compare the two treatment groups with respect to rates of i) all vascular deaths and disabling stroke, ii) all stroke (ischemic and hemorrhagic), iii) fatal and nonfatal ischemic stroke, iv) all ischemic stroke, myocardial infarction and vascular death, v) all major systemic and any intracranial hemorrhage, vi) all ischemic stroke in the territory of the stenotic intracranial artery. Conclusion. This study will 1) define optimal medical therapy for patients with symptomatic intracranial arterial stenosis, and 2) identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high (i.e., greater than or equal to 6 percent per year) to justify a subsequent trial comparing intracranial angioplasty with best medical therapy in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

A mAb to the [beta]2-leukocyte integrin Mac-1 (CD11b /CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits. by Rogers C, Edelman ER, Simon DI.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21474

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Angioplasty and Stenting of the Extracranial Carotid Arteries. by Henry M, Amor M, Klonaris C, Henry I, Masson I, Chati Z, Leborgne E, Hugel M.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101050

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Can Stent-Angioplasty Be a Valid Alternative to Surgery When Revascularization Is Indicated for Anomalous Origination of a Coronary Artery from the Opposite Sinus? by Hariharan R, Kacere RD, Angelini P.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140293

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Coronary angioplasty and stenting. by Malik I.; 2002 Sep 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121332

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Coronary Angioplasty Induces Rise in Chlamydia pneumoniae-Specific Antibodies. by Tiran A, Tio RA, Ossewaarde JM, Tiran B, den Heijer P, The TH, Wilders-Truschnig MM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88642

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Current Status of Carotid Bifurcation Angioplasty and Stenting. by Krajcer Z.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101166

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Debate: Should the elderly receive thrombolytic therapy or primary angioplasty? by White HD.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59616

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Debate: Should the elderly receive thrombolytic therapy, or primary angioplasty, for acute myocardial infarction? The case for primary angioplasty. by DeGeare VS, Grines CL.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59621

3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

Design of a randomized controlled trial of comprehensive rehabilitation in patients with myocardial infarction, stabilized acute coronary syndrome, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting: Akershus Comprehensive Cardiac Rehabilitation Trial (the CORE Study). by Pater C, Ditlef Jacobsen C, Rollag A, Sandvik L, Erikssen J, Karin Kogstad E.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56205

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Humoral Immune Response to Human Cytomegalovirus in Patients Undergoing Percutaneous Transluminal Coronary Angioplasty. by Tiran A, Tio RA, Oostenveld E, Harmsen MC, Tiran B, Den Heijer P, Monnink SH, Wilders-Truschnig MM, The TH.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95658

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Impact of the "Stent-When-Feasible" Policy on In-Hospital and 6-Month Success and Complication Rates after Coronary Angioplasty: Single-Center Experience with 17,956 Revascularization Procedures (1993 --1997). by Angelini P, Vaughn WK, Zaqqa M, Wilson JM, Fish RD.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101101

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Is transfer for primary angioplasty better than on-site fibrinolytic therapy for acute myocardial infarction? by Choi S.; 2003 Sep 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=202290

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Percutaneous transluminal coronary angioplasty versus medical treatment for nonacute coronary heart disease: meta-analysis of randomised controlled trials. by Bucher HC, Hengstler P, Schindler C, Guyatt GH.; 2000 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27425

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Potential roles of osteopontin and [alpha]V[beta]3integrin in the development of coronary artery restenosis after angioplasty. by Panda D, Kundu GC, Lee BI, Peri A, Fohl D, Chackalaparampil I, Mukherjee BB, Li XD, Mukherjee DC, Seides S, Rosenberg J, Stark K, Mukherjee AB.; 1997 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23171

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Primary angioplasty for ST-segment elevation myocardial infarction: Ready for prime time? by Natarajan MK, Yusuf S.; 2003 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164940

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Surgical Management of Entrapped Percutaneous Transluminal Coronary Angioplasty Hardware. by Chang TM, Pellegrini D, Ostrovsky A, Marrangoni AG.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140298

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web 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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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 angioplasty, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “angioplasty” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for angioplasty (hyperlinks lead to article summaries): •

A break-even price calculation for the use of sirolimus-eluting stents in angioplasty. Author(s): Galanaud JP, Delavennat J, Durand-Zaleski I. Source: Clinical Therapeutics. 2003 March; 25(3): 1007-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852715&dopt=Abstract

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A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. Author(s): Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, Villadsen AB, Krusell LR, Haghfelt T, Lomholt P, Husted SE, Vigholt E, Kjaergard HK, Mortensen LS; DANAMI-2 Investigators. Source: The New England Journal of Medicine. 2003 August 21; 349(8): 733-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930925&dopt=Abstract

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A critical amendment to the meta-analysis of clinical trials comparing thrombolysis with primary angioplasty. Author(s): Thimme M. Source: European Heart Journal. 2003 October; 24(20): 1898; Author Reply 1898. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563346&dopt=Abstract

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A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes. Author(s): Hoffman SN, TenBrook JA, Wolf MP, Pauker SG, Salem DN, Wong JB. Source: Journal of the American College of Cardiology. 2003 April 16; 41(8): 1293-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706924&dopt=Abstract

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A model of primary atherosclerosis and post-angioplasty restenosis in mice. Author(s): Leidenfrost JE, Khan MF, Boc KP, Villa BR, Collins ET, Parks WC, Abendschein DR, Choi ET. Source: American Journal of Pathology. 2003 August; 163(2): 773-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875996&dopt=Abstract

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A new concept for covered stent protected carotid angioplasty: an ex vivo study. Author(s): Muller-Hulsbeck S, Jahnke T, Stolzmann P, Paulsen F, Wenke R, Heller M. Source: Rofo. Fortschritte Auf Dem Gebiete Der Rontgenstrahlen Und Der Neuen Bildgebenden Verfahren. 2003 December; 175(12): 1634-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14661133&dopt=Abstract

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A preliminary investigation of balloon angioplasty versus surgical treatment of thrombosed dialysis access grafts. Author(s): McCutcheon B, Weatherford D, Maxwell G, Hamann MS, Stiles A. Source: The American Surgeon. 2003 August; 69(8): 663-7; Discussion 668. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953823&dopt=Abstract

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A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival. Author(s): Tessitore N, Mansueto G, Bedogna V, Lipari G, Poli A, Gammaro L, Baggio E, Morana G, Loschiavo C, Laudon A, Oldrizzi L, Maschio G. Source: Journal of the American Society of Nephrology : Jasn. 2003 June; 14(6): 1623-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761264&dopt=Abstract

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A randomized comparison of repeat stenting with balloon angioplasty in patients with in-stent restenosis. Author(s): Alfonso F, Zueco J, Cequier A, Mantilla R, Bethencourt A, Lopez-Minguez JR, Angel J, Auge JM, Gomez-Recio M, Moris C, Seabra-Gomes R, Perez-Vizcayno MJ, Macaya C; Restenosis Intra-stent: Balloon Angioplasty Versus Elective Stenting (RIBS) Investigators. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 796-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957423&dopt=Abstract

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A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 Delivery for Myocardial Infarction REduction) study. Author(s): Kopecky SL, Aviles RJ, Bell MR, Lobl JK, Tipping D, Frommell G, Ramsey K, Holland AE, Midei M, Jain A, Kellett M, Gibbons RJ; AmP579 Delivery for Myocardial Infarction REduction study. Source: American Heart Journal. 2003 July; 146(1): 146-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851624&dopt=Abstract

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A rare case of aortocoronary dissection following percutaneous transluminal coronary angioplasty: successful treatment using off-pump coronary artery bypass grafting. Author(s): Bapat VN, Venn GE. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 August; 24(2): 312-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895633&dopt=Abstract

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A reappraisal of angioplasty and stenting for the treatment of vertebral origin stenosis. Author(s): Albuquerque FC, Fiorella D, Han P, Spetzler RF, McDougall CG. Source: Neurosurgery. 2003 September; 53(3): 607-14; Discussion 614-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943577&dopt=Abstract

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A refined angioplasty and stenting technique may offer an alternative to carotid endarterectomy. Author(s): Gandhi S, Candipan R. Source: The Journal of Cardiovascular Nursing. 2003 November-December; 18(5): 343-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14680336&dopt=Abstract

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Abciximab reduces monocyte tissue factor in carotid angioplasty and stenting. Author(s): Kopp CW, Steiner S, Nasel C, Seidinger D, Mlekusch I, Lang W, Bartok A, Ahmadi R, Minar E. Source: Stroke; a Journal of Cerebral Circulation. 2003 November; 34(11): 2560-7. Epub 2003 October 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563968&dopt=Abstract

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Access flow measurement during surveillance and percutaneous transluminal angioplasty intervention. Author(s): Krivitski NM. Source: Seminars in Dialysis. 2003 July-August; 16(4): 304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839504&dopt=Abstract

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Activation of circulating platelets in patients with peripheral arterial disease during digital subtraction angiography and percutaneous transluminal angioplasty. Author(s): Buchholz AM, Bruch L, Schulte KL. Source: Thrombosis Research. 2003 January 1; 109(1): 13-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679127&dopt=Abstract

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Acute and long-term outcomes of cutting balloon angioplasty followed by gamma brachytherapy for in-stent restenosis. Author(s): Kobayashi Y, Mehran R, Mintz GS, Dangas G, Moussa I, Collins M, Brara P, Moussavian M, Lansky AJ, Stone GW, Leon MB, Moses JW, Teirstein PS. Source: The American Journal of Cardiology. 2003 December 1; 92(11): 1329-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636914&dopt=Abstract

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Acute myocardial infarction complicated by early onset of heart failure: safety and feasibility of interhospital transfer for coronary angioplasty. Subanalysis of Killip IIIV patients from the PRAGUE-1 study. Author(s): Bednar F, Widimsky P, Groch L, Aschermann M, Zelizko M, Krupicka J; PRAGUE-1 Study Group Investigators. Source: Journal of Interventional Cardiology. 2003 June; 16(3): 201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800397&dopt=Abstract

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Acute myocardial infarction: patient selection for reperfusion with coronary angioplasty. Author(s): Cafri C, Crystal E, Kobal S, Weinstein JM, Gilutz H, Ilia R. Source: Isr Med Assoc J. 2003 April; 5(4): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509126&dopt=Abstract

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Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial. Author(s): Lee DP, Herity NA, Hiatt BL, Fearon WF, Rezaee M, Carter AJ, Huston M, Schreiber D, DiBattiste PM, Yeung AC; TIrofiban Given in the Emergency Room before Primary Angioplasty. Source: Circulation. 2003 March 25; 107(11): 1497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654606&dopt=Abstract

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Adjunctive use of platelet glycoprotein IIb/IIIa inhibitors for carotid angioplasty and stent placement: time to say good bye? Author(s): Qureshi AI. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 February; 10(1): 42-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751928&dopt=Abstract

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Administration of atrial natriuretic peptide attenuates reperfusion phenomena and preserves left ventricular regional wall motion after direct coronary angioplasty for acute myocardial infarction. Author(s): Kuga H, Ogawa K, Oida A, Taguchi I, Nakatsugawa M, Hoshi T, Sugimura H, Abe S, Kaneko N. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 May; 67(5): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736485&dopt=Abstract

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Age and lack of beta-blocker therapy are associated with increased long-term mortality after primary coronary angioplasty for acute myocardial infarction. Author(s): Juliard JM, Charlier P, Golmard JL, Himbert D, Aubry P, Benamer H, Feldman LJ, Karila-Cohen D, Steg PG. Source: International Journal of Cardiology. 2003 March; 88(1): 63-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659986&dopt=Abstract

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An updated meta-analysis of calcium-channel blockers in the prevention of restenosis after coronary angioplasty. Author(s): Dens J, Desmet W, Piessens J. Source: American Heart Journal. 2003 March; 145(3): 404-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660661&dopt=Abstract

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Analysis of the institutional volume-outcome relations for balloon angioplasty and stenting in the stent era in California. Author(s): Brown DL. Source: American Heart Journal. 2003 December; 146(6): 1071-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14661001&dopt=Abstract

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Angioplasty and coiling of ruptured aneurysm with symptomatic vasospasm: technical case report. Author(s): Sugiu K, Katsumata A, Ono Y, Tamiya T, Ohmoto T. Source: Surgical Neurology. 2003 May; 59(5): 413-7; Discussion 417. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765821&dopt=Abstract

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Angioplasty and elective stenting of de novo versus recurrent femoropopliteal lesions: 1-year follow-up. Author(s): Schillinger M, Mlekusch W, Haumer M, Sabeti S, Ahmadi R, Minar E. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 April; 10(2): 288-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877612&dopt=Abstract

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Angioplasty and primary stenting of high-grade, long-segment superficial femoral artery disease: is it worthwhile? Author(s): Cheng SW, Ting AC, Ho P. Source: Annals of Vascular Surgery. 2003 July; 17(4): 430-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670023&dopt=Abstract

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Angioplasty and stenting. Author(s): Brown MM. Source: Adv Neurol. 2003; 92: 335-45. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760200&dopt=Abstract

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Angioplasty for chronic total occlusion by using tapered-tip guidewires. Author(s): Saito S, Tanaka S, Hiroe Y, Miyashita Y, Takahashi S, Satake S, Tanaka K. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 July; 59(3): 305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822146&dopt=Abstract

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Angioplasty for intracranial atherosclerosis: is the treatment worse than the disease? Author(s): Chaturvedi S, Caplan LR. Source: Neurology. 2003 December 23; 61(12): 1647-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14694023&dopt=Abstract

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Angioplasty in a patient with ocular ischemia due to occlusion of the internal and stenosis of the external carotid artery. Author(s): Weber JF, Kirsch E, Radu EW, Steck AJ, Kaiser HJ, Lyrer PA. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16(4): 436-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130189&dopt=Abstract

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Angioplasty in acute myocardial infarction after low-dose alteplase and abciximab in transferred patients. A comparison with primary angioplasty on site. Author(s): Manari A, Guiducci V, Muia N, Giacometti P, Fioroni S, Navazio A, Gambarati G, Bendinelli S, Bruno G. Source: Ital Heart J. 2003 May; 4(5): 311-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848087&dopt=Abstract

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Angioplasty in the diabetic patient. Author(s): Van Belle E, Chmait A, Bauters C, Lablanche JM. Source: J Invasive Cardiol. 2004 January; 16(1): 23-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14699219&dopt=Abstract

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Angioplasty or stenting in adult coarctation of the aorta? A retrospective single center analysis over a decade. Author(s): Macdonald S, Thomas SM, Cleveland TJ, Gaines PA. Source: Cardiovascular and Interventional Radiology. 2003 July-August; 26(4): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667117&dopt=Abstract

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Angioplasty, C-reactive protein, and the patient at risk. Author(s): McCowan TC, Eidt JF. Source: Radiology. 2003 May; 227(2): 314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732692&dopt=Abstract

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Angioplasty, inflammation, and antiplatelet agents. Author(s): Moliterno DJ, Penn MS. Source: American Heart Journal. 2003 April; 145(4): 563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679746&dopt=Abstract

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Anxiety and well-being in first-time coronary angioplasty patients and repeaters. Author(s): Lenzen MJ, Gamel CJ, Immink AW. Source: European Journal of Cardiovascular Nursing : Journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology. 2002 October; 1(3): 195201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622674&dopt=Abstract

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Assessing risk for major depression on patients selected for percutaneous transluminal coronary angioplasty: is it a worthwhile venture? Author(s): Burton HJ, Kline SA, Cooper BS, Rabinowitz A, Dodek A. Source: General Hospital Psychiatry. 2003 May-June; 25(3): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748033&dopt=Abstract

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Association of cholesterol levels and occurrence of angiographically detectable endothelial disruption during coronary angioplasty. Author(s): Rubboli A, Euler DE, Sangiorgio P, Casella G, La Vechia L, Fontanelli A, Bracchetti D. Source: Clin Cardiol. 2003 July; 26(7): 336-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862300&dopt=Abstract

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Balloon angioplasty as a treatment of failing infrainguinal autologous vein bypass grafts. Author(s): Carlson GA, Hoballah JJ, Sharp WJ, Martinasevic M, Maiers Yelden K, Corson JD, Kresowik TF. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2004 February; 39(2): 421-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14743147&dopt=Abstract

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Balloon angioplasty versus medical therapy for hypertensive patients with renal artery obstruction. Author(s): Nordmann AJ, Logan AG. Source: Cochrane Database Syst Rev. 2003; (3): Cd002944. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917937&dopt=Abstract

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Beneficial outcome after angioplasty of unprotected left main stenosis in patients during resuscitation. Author(s): Empen K, Bollmann T, Dahm JB. Source: Circulation. 2003 April 8; 107(13): E91; Author Reply E91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682037&dopt=Abstract

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Benefits and risks of abciximab use in primary angioplasty for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Author(s): Tcheng JE, Kandzari DE, Grines CL, Cox DA, Effron MB, Garcia E, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Fahy M, Lansky AJ, Mehran R, Stone GW; CADILLAC Investigators. Source: Circulation. 2003 September 16; 108(11): 1316-23. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939213&dopt=Abstract

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Benefits of direct angioplasty for women and men with acute myocardial infarction: results of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes Angioplasty (GUSTO II-B) Angioplasty Substudy. Author(s): Tamis-Holland JE, Palazzo A, Stebbins AL, Slater JN, Boland J, Ellis SG, Hochman JS; GUSTO II-B Angioplasty Substudy Investigators. Source: American Heart Journal. 2004 January; 147(1): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14691431&dopt=Abstract

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Beta-blocker use in the emergency department in patients with acute myocardial infarction undergoing primary angioplasty. Author(s): Pancu D, Lee DC. Source: The Journal of Emergency Medicine. 2003 May; 24(4): 379-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745038&dopt=Abstract

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Candidate genetic markers and the risk of restenosis after coronary angioplasty. Author(s): Volzke H, Grimm R, Robinson DM, Wolff B, Schwahn C, Hertwig S, Motz W, Rettig R. Source: Clinical Science (London, England : 1979). 2004 January; 106(1): 35-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899665&dopt=Abstract

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Carotid angioplasty and stenting in high-risk patients with severe symptomatic carotid stenosis. Author(s): Ballotta E, Da Giau G, Baracchini C. Source: Stroke; a Journal of Cerebral Circulation. 2003 April; 34(4): 834-5; Author Reply 834-5. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663873&dopt=Abstract

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Carotid angioplasty and stenting with and without cerebral protection: clinical alert from the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial. Author(s): Mas JL, Chatellier G, Beyssen B; EVA-3S Investigators. Source: Stroke; a Journal of Cerebral Circulation. 2004 January; 35(1): E18-20. Epub 2003 December 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657456&dopt=Abstract

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Carotid angioplasty in a pulsatile flow model: factors affecting embolic potential. Author(s): Bicknell CD, Cowling MG, Clark MW, Delis KT, Jenkins MP, Hughes AD, Thom SA, Wolfe JH, Cheshire NJ. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 July; 26(1): 22-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819644&dopt=Abstract

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Carotid angioplasty with stenting and carotid endarterectomy for high-risk patients. Author(s): Lucertini G. Source: Stroke; a Journal of Cerebral Circulation. 2003 June; 34(6): E42-3; Author Reply E42-3. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750531&dopt=Abstract

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Carotid artery angioplasty and stent placement: quality improvement guidelines to ensure stroke risk reduction. Author(s): Connors JJ 3rd, Sacks D, Becker GJ, Barr JD. Source: Journal of Vascular and Interventional Radiology : Jvir. 2003 September; 14(9 Pt 1): 1095-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514798&dopt=Abstract

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Carotid artery angioplasty for restenosis following endarterectomy. Author(s): McDonnell CO, Legge D, Twomey E, Kavanagh EG, Dundon S, O'Donohoe MK, O'Malley MK, Corrigan TP. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2004 February; 27(2): 163-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14718898&dopt=Abstract

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Changes in the response of hibernated myocardium to inotropic stimulation after angioplasty: a Doppler myocardial imaging study. Author(s): Klisiewicz A, Michalek P, Szymanski P, Hoffman P. Source: Clin Cardiol. 2003 November; 26(11): 503-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640464&dopt=Abstract

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Clinical and angiographic outcome after cutting balloon angioplasty. Author(s): Auer J, Maurer E, Berent R, Mayr H, Punzengruber C, Weber T, Lassnig E, Eber B. Source: Journal of Interventional Cardiology. 2003 February; 16(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664813&dopt=Abstract

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Clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting. Implications for mechanical plaque sealing. Author(s): Mercado N, Maier W, Boersma E, Bucher C, de Valk V, O'Neill WW, Gersh BJ, Meier B, Serruys PW, Wijns W. Source: European Heart Journal. 2003 March; 24(6): 541-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643887&dopt=Abstract

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Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure. Author(s): Gray BH, Olin JW, Childs MB, Sullivan TM, Bacharach JM. Source: Vascular Medicine (London, England). 2002; 7(4): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710843&dopt=Abstract

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Clinical outcome following combination of cutting balloon angioplasty and coronary beta-radiation for in-stent restenosis: a report from the RENO registry. Author(s): Roguelov C, Eeckhout E, De Benedetti E, Coucke P, Silber S, Baumgart D, Albiero R, Bonan R, Wegscheider K, Urban P; RENO Registry Investigators. Source: J Invasive Cardiol. 2003 December; 15(12): 706-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14660823&dopt=Abstract

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Clinical outcome following infra-inguinal percutaneous transluminal angioplasty for critical limb ischemia. Author(s): Matsagas MI, Rivera MA, Tran T, Mitchell A, Robless P, Davies AH, Geroulakos G. Source: Cardiovascular and Interventional Radiology. 2003 May-June; 26(3): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562973&dopt=Abstract

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Clinical outcome of coronary angioplasty in patients with ischaemic cardiomyopathy. Author(s): Bukachi F, Clague JR, Waldenstrom A, Kazzam E, Henein MY. Source: International Journal of Cardiology. 2003 April; 88(2-3): 167-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714195&dopt=Abstract

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Clinical significance of acute-phase brain natriuretic peptide in acute myocardial infarction treated with direct coronary angioplasty. Author(s): Katayama T, Nakashima H, Yonekura T, Honda Y, Suzuki S, Yano K. Source: J Cardiol. 2003 November; 42(5): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658407&dopt=Abstract

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Color Doppler ultrasound guidance during renal angioplasty and stenting. Author(s): Cianci R, Zaccaria A, Lai S, Coen G, Mander A, Manfredini P, Minnetti M, Clemenzia G, Fiorani P. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 April; 10(2): 357-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877623&dopt=Abstract

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Comparison of effectiveness of excimer laser angioplasty in patients with acute coronary syndromes in those with versus those without normal left ventricular function. Author(s): Topaz O, Minisi AJ, Bernardo N, Alimar R, Ereso A, Shah R. Source: The American Journal of Cardiology. 2003 April 1; 91(7): 797-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667563&dopt=Abstract

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Comparison of nonneurological events in high-risk patients treated by carotid angioplasty versus endarterectomy. Author(s): Kasirajan K, Matteson B, Marek JM, Langsfeld M. Source: American Journal of Surgery. 2003 April; 185(4): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657378&dopt=Abstract

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Comparison of outcomes for patients undergoing balloon angioplasty vs coronary stenting for acute myocardial infarction. Author(s): Tsuchihashi M, Tsutsui H, Shihara M, Tada H, Kono S, Takeshita A; Japanese Coronary Intervention Study. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 May; 67(5): 369-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736471&dopt=Abstract

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Comparison of outcomes of diabetic and nondiabetic patients undergoing primary angioplasty for acute myocardial infarction. Author(s): Harjai KJ, Stone GW, Boura J, Mattos L, Chandra H, Cox D, Grines L, O'Neill W, Grines C; Primary Angioplasty in Myocardial Infarction Investigators. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1041-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714143&dopt=Abstract

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Comparison of rotational atherectomy with conventional balloon angioplasty in the prevention of restenosis of small coronary arteries: results of the Dilatation vs Ablation Revascularization Trial Targeting Restenosis (DART). Author(s): Mauri L, Reisman M, Buchbinder M, Popma JJ, Sharma SK, Cutlip DE, Ho KK, Prpic R, Zimetbaum PJ, Kuntz RE. Source: American Heart Journal. 2003 May; 145(5): 847-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766743&dopt=Abstract

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Comparison of short- and long-term outcomes of coronary angioplasty in patients with and without diabetes mellitus and with and without hemodialysis. Author(s): Le Feuvre C, Borentain M, Beygui F, Helft G, Batisse JP, Metzger JP. Source: The American Journal of Cardiology. 2003 September 15; 92(6): 721-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972118&dopt=Abstract

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Coronary angioplasty versus fibrinolytic therapy in acute myocardial infarction. Author(s): Armstrong PW, Antman EM. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2167-9; Author Reply 2167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658129&dopt=Abstract

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Coronary angioplasty versus fibrinolytic therapy in acute myocardial infarction. Author(s): Zaman AG. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2167-9; Author Reply 2167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658128&dopt=Abstract

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Coronary angioplasty versus fibrinolytic therapy in acute myocardial infarction. Author(s): Channer KS. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2167-9; Author Reply 2167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645648&dopt=Abstract

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Coronary angioplasty--have we conquered restenosis? Author(s): Mishra A. Source: J Indian Med Assoc. 2003 April; 101(4): 225-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964637&dopt=Abstract

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Coronary rupture as a rare cause of acute myocardial ischaemia two months after angioplasty and stenting. Author(s): Tsui KL, Lam KH, Li SK. Source: Heart (British Cardiac Society). 2003 November; 89(11): 1315. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594887&dopt=Abstract

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Coronary stent implantation is superior to balloon angioplasty for chronic coronary occlusions: six-year clinical follow-up of the GISSOC trial. Author(s): Rubartelli P, Verna E, Niccoli L, Giachero C, Zimarino M, Bernardi G, Vassanelli C, Campolo L, Martuscelli E; Gruppo Italiano di Studio sullo Stent nelle Occlusioni Coronariche Investigators. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1488-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742287&dopt=Abstract

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Coronary stenting after rotational atherectomy in diffuse lesions of the small coronary artery: comparison with balloon angioplasty before stenting. Author(s): Kwon K, Choi D, Choi SH, Koo BK, Jang Y, Shim WH, Cho SY. Source: Angiology. 2003 July-August; 54(4): 423-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934762&dopt=Abstract

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Coronary stenting after rotational atherectomy in diffuse lesions of the small coronary artery: comparison with balloon angioplasty prior to stenting. Author(s): Kwon K, Choi D, Kwon Koo B, Kee Ryu S, Ko YG, Jang Y, Shim WH, Cho SY. Source: International Journal of Cardiology. 2003 June; 89(2-3): 299-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767557&dopt=Abstract

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Cost-effectiveness of coronary stenting and abciximab for patients with acute myocardial infarction: results from the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial. Author(s): Bakhai A, Stone GW, Grines CL, Murphy SA, Githiora L, Berezin RH, Cox DA, Stuckey T, Griffin JJ, Tcheng JE, Cohen DJ; CADILLAC Investigators. Source: Circulation. 2003 December 9; 108(23): 2857-63. Epub 2003 November 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14610016&dopt=Abstract

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Covered stent: a novel percutaneous treatment of iatrogenic aortic dissection during coronary angioplasty. Author(s): Abu-Ful A, Weinstein JM, Henkin Y. Source: J Invasive Cardiol. 2003 July; 15(7): 408-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840241&dopt=Abstract

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C-reactive protein and coronary events following percutaneous coronary angioplasty. Author(s): de Winter RJ, Koch KT, van Straalen JP, Heyde G, Bax M, Schotborgh CE, Mulder KJ, Sanders GT, Fischer J, Tijssen JG, Piek JJ. Source: The American Journal of Medicine. 2003 August 1; 115(2): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893392&dopt=Abstract

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Cutting balloon angioplasty for undilatable venous stenoses causing dialysis graft failure. Author(s): Bittl JA, Feldman RL. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 April; 58(4): 524-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652505&dopt=Abstract

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Cyclic variation of myocardial integrated backscatter and myocardial wall thickness during percutaneous coronary angioplasty. Author(s): Tekten T, Onbasili AO, Ceyhan C, Discigil B. Source: Echocardiography (Mount Kisco, N.Y.). 2003 July; 20(5): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848861&dopt=Abstract

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Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2). Author(s): Andersen HR, Nielsen TT, Vesterlund T, Grande P, Abildgaard U, Thayssen P, Pedersen F, Mortensen LS; DANAMI-2 Investigators. Source: American Heart Journal. 2003 August; 146(2): 234-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891190&dopt=Abstract

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Delayed recovery of left ventricular regional work after coronary angioplasty in patients with opposite wall old myocardial infarction. Author(s): Isobe N, Sugawara M, Taniguchi K, Oshima S, Hoshizaki H, Toyama T, Adachi H, Naito S. Source: Heart and Vessels. 2003 May; 18(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756601&dopt=Abstract

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Development of a water-soluble matrix metalloproteinase inhibitor as an intraarterial infusion drug for prevention of restenosis after angioplasty. Author(s): Masuda T, Nakayama Y. Source: Journal of Medicinal Chemistry. 2003 July 31; 46(16): 3497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877587&dopt=Abstract

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Dissolution of a huge spontaneous coronary artery thrombus with a new antiplatelet agent and coronary angioplasty. Author(s): Akdemir R, Uyan C. Source: International Journal of Cardiology. 2003 May; 89(1): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727009&dopt=Abstract

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Do protection devices have a role in renal angioplasty and stent placement? Author(s): Scoble JE. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 September; 18(9): 1700-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937212&dopt=Abstract

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Early direct coronary angioplasty in survivors of out-of-hospital cardiac arrest. Author(s): Keelan PC, Bunch TJ, White RD, Packer DL, Holmes DR Jr. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1461-3, A6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804734&dopt=Abstract

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Effect of carotid angioplasty-stenting on short-term mortality and stroke. Author(s): Pucillo AL, Mateo RB, Aronow WS. Source: Heart Disease. 2003 November-December; 5(6): 378-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14633319&dopt=Abstract

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Effect of monitoring of physician performance on door-to-balloon time for primary angioplasty in acute myocardial infarction. Author(s): Shry EA, Eckart RE, Winslow JB, Rollefson WA, Simpson DE. Source: The American Journal of Cardiology. 2003 April 1; 91(7): 867-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667574&dopt=Abstract

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Effect of postmenopausal hormone therapy on coronary heart disease events after percutaneous transluminal coronary angioplasty. Author(s): Khan MA, Hlatky MA, Liu MW, Lin F, Rogers WJ, Shlipak MG; HERS Investigators. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 989-91, A7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686345&dopt=Abstract

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Effect of successful late reperfusion by primary coronary angioplasty on mechanical complications of acute myocardial infarction. Author(s): Nakatani D, Sato H, Kinjo K, Mizuno H, Hishida E, Hirayama A, Mishima M, Ito H, Matsumura Y, Hori M; Osaka Acute Coronary Insufficiency Study Group. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 785-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516876&dopt=Abstract

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Effect of tirofiban before primary angioplasty on initial coronary flow and early STsegment resolution in patients with acute myocardial infarction. Author(s): Cutlip DE, Ricciardi MJ, Ling FS, Carrozza JP Jr, Dua V, Garringer J, Giri S, Caputo RP. Source: The American Journal of Cardiology. 2003 October 15; 92(8): 977-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556878&dopt=Abstract

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Effects of amlodipine on ischemia after percutaneous transluminal coronary angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis (CAPARES) Study. Author(s): Jorgensen B, Thaulow E; Coronary Angioplasty Amlodipine Restenosis Study. Source: American Heart Journal. 2003 June; 145(6): 1030-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796759&dopt=Abstract

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Effects of diltiazem on platelet activation and cytosolic calcium during percutaneous transluminal coronary angioplasty. Author(s): Dai H, Chen J, Tao Q, Zhu J, Zhang F, Zheng L, Qiu Y. Source: Postgraduate Medical Journal. 2003 September; 79(935): 522-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679549&dopt=Abstract

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Effects of glucose-insulin-potassium solution on myocardial salvage and left ventricular function after primary angioplasty. Author(s): Castro PF, Larrain G, Baeza R, Corbalan R, Nazzal C, Greig DP, Miranda FP, Perez O, Acevedo M, Marchant E, Olea E, Gonzalez R. Source: Critical Care Medicine. 2003 August; 31(8): 2152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973173&dopt=Abstract

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Elective versus provisional intra-aortic balloon pumping in high-risk percutaneous transluminal coronary angioplasty. Author(s): Briguori C, Sarais C, Pagnotta P, Airoldi F, Liistro F, Sgura F, Spanos V, Carlino M, Montorfano M, Di Mario C, Colombo A. Source: American Heart Journal. 2003 April; 145(4): 700-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679768&dopt=Abstract

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Elevated whole-blood tissue factor procoagulant activity as a marker of restenosis after percutaneous transluminal coronary angioplasty and stent implantation. Author(s): Tutar E, Ozcan M, Kilickap M, Gulec S, Aras O, Pamir G, Oral D, Dandelet L, Key NS. Source: Circulation. 2003 September 30; 108(13): 1581-4. Epub 2003 Sep 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975255&dopt=Abstract

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Emergency surgery after unsuccessful coronary angioplasty: a review of 15 years' experience. Author(s): Barakate MS, Bannon PG, Hughes CF, Horton MD, Callaway A, Hurst T. Source: The Annals of Thoracic Surgery. 2003 May; 75(5): 1400-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735553&dopt=Abstract

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Endovascular brachytherapy after percutaneous transluminal angioplasty of recurrent femoropopliteal obstructions. Author(s): Zehnder T, von Briel C, Baumgartner I, Triller J, Greiner R, Mahler F, Do DD. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 April; 10(2): 304-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877614&dopt=Abstract

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Endovascular management of symptomatic vertebral artery dissection achieved using stent angioplasty and emboli protection device. Author(s): Cohen JE, Gomori JM, Umansky F. Source: Neurological Research. 2003 June; 25(4): 418-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870271&dopt=Abstract

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Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement. Author(s): Terada T, Tsuura M, Matsumoto H, Masuo O, Tsumoto T, Yamaga H, Itakura T. Source: Journal of Neurosurgery. 2003 March; 98(3): 491-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650419&dopt=Abstract

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Evaluation of glycoprotein IIb/IIIa inhibitors in carotid angioplasty and stenting. Author(s): Wholey MH, Wholey MH, Eles G, Toursakissian B, Bailey S, Jarmolowski C, Tan WA. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 February; 10(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751927&dopt=Abstract

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Evaluation of vascular injury following percutaneous transluminal coronary angioplasty: a comparison of the accuracy of two- and three-dimensional intracoronary ultrasound imaging. Author(s): Palmer ND, Lessells A, Northridge DB, Fox KA. Source: Coronary Artery Disease. 2003 May; 14(3): 255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702930&dopt=Abstract

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Factors influencing fluoroscopy time and dose-area product values during ad hoc onevessel percutaneous coronary angioplasty. Author(s): Larrazet F, Dibie A, Philippe F, Palau R, Klausz R, Laborde F. Source: The British Journal of Radiology. 2003 July; 76(907): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857707&dopt=Abstract

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First case reports of controlled blunt microdissection for percutaneous transluminal angioplasty of chronic total occlusions in peripheral arteries. Author(s): Mossop P, Cincotta M, Whitbourn R. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 June; 59(2): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772253&dopt=Abstract

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Focused force angioplasty: theory and application. Author(s): Solar RJ, Ischinger TA. Source: Cardiovascular Radiation Medicine. 2003 January-March; 4(1): 47-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892774&dopt=Abstract

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Freedom from secondary interventions to treat stenotic disease after percutaneous transluminal angioplasty of infrarenal aorta: long-term results. Author(s): de Vries JP, van Den Heuvel DA, Vos JA, van Den Berg JC, Moll FI. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2004 February; 39(2): 427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14743148&dopt=Abstract

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Frequency, determinants, and clinical implications of residual intracoronary thrombus following primary angioplasty for acute myocardial infarction. Author(s): Harjai KJ, Grines C, Stone GW, Boura J, Turco M, Brodie B, Sadeghi HM, Cox D, Grines L, O' Neill WW. Source: The American Journal of Cardiology. 2003 August 15; 92(4): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914865&dopt=Abstract

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Frequent embolization in peripheral angioplasty: detection with an embolism protection device (AngioGuard) and electron microscopy. Author(s): Konig CW, Pusich B, Tepe G, Wendel HP, Hahn U, Schneider W, Claussen CD, Duda SH. Source: Cardiovascular and Interventional Radiology. 2003 July-August; 26(4): 334-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667114&dopt=Abstract

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Gap between clinical trials and clinical practice: lessons from the Bypass Angioplasty Revascularization Investigation (BARI). Author(s): Frye RL, Brooks MM, Nesto RW; Bypass Angioplasty Revascularization Investigation. Source: Circulation. 2003 April 15; 107(14): 1837-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695282&dopt=Abstract

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Genetic risk markers for post-angioplasty restenosis: what should we expect? Author(s): Green FR. Source: Clinical Science (London, England : 1979). 2004 January; 106(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962537&dopt=Abstract

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Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. Author(s): van der Horst IC, Zijlstra F, van't Hof AW, Doggen CJ, de Boer MJ, Suryapranata H, Hoorntje JC, Dambrink JH, Gans RO, Bilo HJ; Zwolle Infarct Study Group. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 784-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957421&dopt=Abstract

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High preprocedural non-HDL cholesterol is associated with enhanced oxidative stress and monocyte activation after coronary angioplasty: possible implications in restenosis. Author(s): Cipollone F, Fazia M, Iezzi A, Pini B, Costantini F, De Cesare D, Paloscia L, Materazzo G, D'Annunzio E, Bucciarelli T, Vecchiet J, Chiarelli F, Cuccurullo F, Mezzetti A. Source: Heart (British Cardiac Society). 2003 July; 89(7): 773-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807855&dopt=Abstract

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Histopathological evaluation of middle cerebral artery after percutaneous intracranial transluminal angioplasty. Author(s): Schumacher HC, Tanji K, Mangla S, Meyers P, Pile-Spellman J, Hays AP, Mohr JP. Source: Stroke; a Journal of Cerebral Circulation. 2003 September; 34(9): E170-3. Epub 2003 August 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907816&dopt=Abstract

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Immediate and long-term outcome of upper extremity balloon angioplasty in giant cell arteritis. Author(s): Amann-Vesti BR, Koppensteiner R, Rainoni L, Pfamatter T, Schneider E. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 April; 10(2): 371-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877626&dopt=Abstract

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Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: a report from the NHLBI Dynamic Registry. Author(s): Cohen HA, Williams DO, Holmes DR Jr, Selzer F, Kip KE, Johnston JM, Holubkov R, Kelsey SF, Detre KM; NHLBI Dynamic Registry. Source: American Heart Journal. 2003 September; 146(3): 513-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947372&dopt=Abstract

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Impact of barotrauma on acute and late angiographic and clinical outcomes following angioplasty and beta-irradiation of coronary in-stent restenotic lesions. Author(s): Schiele TM, Konig A, Rieber J, Krotz F, Sohn HY, Kantlehner R, Pollinger B, Duhmke E, Theisen K, Siebert U, Klauss V. Source: J Invasive Cardiol. 2004 January; 16(1): 14-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14699217&dopt=Abstract

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Impact of renal insufficiency in patients undergoing primary angioplasty for acute myocardial infarction. Author(s): Sadeghi HM, Stone GW, Grines CL, Mehran R, Dixon SR, Lansky AJ, Fahy M, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Stuckey TD, Turco M, Carroll JD. Source: Circulation. 2003 December 2; 108(22): 2769-75. Epub 2003 November 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638545&dopt=Abstract

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Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial. Author(s): Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY, Cristofini P, Leizorovicz A, Touboul P; Comparison of Angioplasty and Prehospital Thrombolysis In acute Myocardial infarction (CAPTIM) Investigators. Source: Circulation. 2003 December 9; 108(23): 2851-6. Epub 2003 November 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623806&dopt=Abstract

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Increased endogenous endothelin-1 in coronary circulation is associated with restenosis after coronary angioplasty. Author(s): Takase H, Sugiyama M, Nakazawa A, Toriyama T, Hayashi K, Goto T, Sato K, Ikeda K, Ueda R, Dohi Y. Source: The Canadian Journal of Cardiology. 2003 July; 19(8): 902-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876610&dopt=Abstract

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Indications of coronary angioplasty and stenting in 2003: what is left to surgery? Author(s): Poyen V, Silvestri M, Labrunie P, Valeix B. Source: The Journal of Cardiovascular Surgery. 2003 June; 44(3): 307-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832982&dopt=Abstract

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Influence of the Angioplasty Revascularization Investigation National Heart, Lung, and Blood Institute Diabetic Clinical Alert on practice patterns: results from the National Cardiovascular Network Database. Author(s): McGuire DK, Anstrom KJ, Peterson ED. Source: Circulation. 2003 April 15; 107(14): 1864-70. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668513&dopt=Abstract

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In-hospital clinical outcome in elderly patients with acute myocardial infarction treated with primary angioplasty. Author(s): Tespili M, Guagliumi G, Valsecchi O, Musumeci G, Vassileva A, Saino A, Scuri PM, Gavazzi A. Source: Ital Heart J. 2003 March; 4(3): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784746&dopt=Abstract

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Initial experience during balloon angioplasty assisted surgical thrombectomy for thrombosed hemodialysis grafts. Author(s): Ko PJ, Liu YH, Hsieh HC, Chu JJ, Lin PJ. Source: Chang Gung Med J. 2003 March; 26(3): 178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790221&dopt=Abstract

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Insufficient tissue ablation by rotational atherectomy leads to worse long-term results in comparison with balloon angioplasty alone for the treatment of diffuse in-stent restenosis: insights from the intravascular ultrasound substudy of the ARTIST randomized multicenter trial. Author(s): Haager PK, Schiele F, Buettner HJ, Garcia E, Bedossa M, Mudra H, Dietz U, di Mario C, Reineke T, Horn B, Hoffmann R, Radke PW, Klues HG, vom Dahl J; ARTIST Investigators. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 September; 60(1): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929098&dopt=Abstract

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Integrated Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) grafting and angioplasty for coronary artery revascularization. Author(s): Cisowski M, Morawski W, Drzewiecki J, Bochenek A. Source: Heart Surg Forum. 2002; 5 Suppl 4: S282-95. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759203&dopt=Abstract

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Inter-hospital transport for primary angioplasty does not compromise left ventricular function: six-month echocardiographic follow-up of the PRAGUE 1 Study. Author(s): Krupicka J, Widimsky P, Nechvatal L, Bednar F, Linkova H, Gregor P, Groch L, Zelizko M, Aschermann M. Source: Japanese Heart Journal. 2003 May; 44(3): 313-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825799&dopt=Abstract

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Interhospital transport for primary angioplasty improves the long-term outcome of acute myocardial infarction compared with immediate thrombolysis in the nearest hospital (one-year follow-up of the PRAGUE-1 study). Author(s): Bednar F, Widimsky P, Krupicka J, Groch L, Aschermann M, Zelizko M; PRAGUE Study Group Investigators. Source: The Canadian Journal of Cardiology. 2003 September; 19(10): 1133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532938&dopt=Abstract

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Intracoronary beta-irradiation with liquid rhenium-188 to prevent restenosis following pure balloon angioplasty: results from the TRIPPER-1 study. Author(s): Hang CL, Fu M, Hsieh BT, Leung SW, Wu CJ, Ting G. Source: Chang Gung Med J. 2003 February; 26(2): 98-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718386&dopt=Abstract

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Intracoronary beta-irradiation with liquid rhenium-188: results of the Taiwan radiation in prevention of post-pure balloon angioplasty restenosis study. Author(s): Hang CL, Fu M, Hsieh BT, Leung SW, Wu CJ, Yip HK, Ting G. Source: Chest. 2003 October; 124(4): 1284-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555557&dopt=Abstract

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Intracoronary fracture and embolization of a coronary angioplasty balloon catheter: retrieval by a simple technique. Author(s): Trehan V, Mukhopadhyay S, Yusuf J, C Ramgasetty U, Mukherjee S, Arora R. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 April; 58(4): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652497&dopt=Abstract

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Intracoronary thrombectomy improves myocardial reperfusion in patients undergoing direct angioplasty for acute myocardial infarction. Author(s): Napodano M, Pasquetto G, Sacca S, Cernetti C, Scarabeo V, Pascotto P, Reimers B. Source: Journal of the American College of Cardiology. 2003 October 15; 42(8): 1395-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563581&dopt=Abstract

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Intracranial stent placement for the treatment of a carotid-cavernous fistula associated with intracranial angioplasty. Case report. Author(s): Kim SH, Qureshi AI, Boulos AS, Bendok BR, Levy EL, Yahia AM, Guterman LR, Hopkins LN. Source: Journal of Neurosurgery. 2003 May; 98(5): 1116-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744375&dopt=Abstract

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Intravenous myocardial contrast echocardiography during angioplasty. Author(s): Hagendorff A, Goeckritz A, Neugebauer A, Rother T, Pfeiffer D, Becher H. Source: Echocardiography (Mount Kisco, N.Y.). 2003 August; 20(6): 527-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859365&dopt=Abstract

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Is transfer for primary angioplasty better than on-site fibrinolytic therapy for acute myocardial infarction? Author(s): Choi S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 September 30; 169(7): 695. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517131&dopt=Abstract

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Laboratory monitoring of heparin and the combination of heparin and the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Author(s): Zahn R, Haubelt H, Bechtloff S, Schneider S, Frilling B, Rustige J, Marsalek P, Seidl K, Senges J, Hellstern P. Source: Herz. 2003 August; 28(5): 445-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928744&dopt=Abstract

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Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications. Author(s): David DS. Source: Circulation. 2003 May 27; 107(20): E196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777327&dopt=Abstract

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Left ventricular systolic function in myocardial infarction survivors treated with primary angioplasty, thrombolysis of angioplasty preceded by thrombolysis. Author(s): Gaszewska-Zurek E, Paradowska M, Maslankiewicz K, Gruszka A, Tendera M. Source: Kardiologia Polska. 2003 July; 59(7): 27-37; Discussion 37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560346&dopt=Abstract

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Limb salvage angioplasty in poor surgical candidates. Author(s): Tefera G, Turnipseed W, Tanke T. Source: Vascular and Endovascular Surgery. 2003 March-April; 37(2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669140&dopt=Abstract

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Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction (PRAGUE-2 trial). Author(s): Perez de Arenaza D, Taneja AK, Flather M. Source: European Heart Journal. 2003 October; 24(19): 1798. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522580&dopt=Abstract

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Long-term resource use and cost of percutaneous transluminal coronary angioplasty versus stenting in the elderly: a retrospective claims data analysis. Author(s): Subramanian S, Khandker RK, Roth D. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2003 September-October; 6(5): 534-41; Discussion 532-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627059&dopt=Abstract

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Management of ruptures complicating angioplasty and stenting of supraaortic arteries: report of two cases and a review of the literature. Author(s): Broadbent LP, Moran CJ, Cross DT 3rd, Derdeyn CP. Source: Ajnr. American Journal of Neuroradiology. 2003 November-December; 24(10): 2057-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625233&dopt=Abstract

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Mechanical prevention of distal embolization during primary angioplasty: safety, feasibility, and impact on myocardial reperfusion. Author(s): Limbruno U, Micheli A, De Carlo M, Amoroso G, Rossini R, Palagi C, Di Bello V, Petronio AS, Fontanini G, Mariani M. Source: Circulation. 2003 July 15; 108(2): 171-6. Epub 2003 June 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835216&dopt=Abstract

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Meta-analysis finds angioplasty more effective than thrombolytic therapy in treating heart attack. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 January 24; 14(2): 1-2, 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776698&dopt=Abstract

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Modeling predictors of quality of life after coronary angioplasty. Author(s): Echteld MA, van Elderen T, van der Kamp LJ. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2003 August; 26(1): 49-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867354&dopt=Abstract

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Multivessel cutting balloon angioplasty in a patient with type III nonspecific aortoarteritis. Author(s): Joseph G, Pati PK, Mathews P. Source: Indian Heart J. 2003 March-April; 55(2): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921335&dopt=Abstract

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Myocardial infarction in patients with diabetes. Results of primary coronary angioplasty. Author(s): Gasior M, Wasilewski J, Gierlotka M, Zebik T, Lekston A, Wojnar R, Kondys M, Szkodzinski J, Wilczek K, Wnek A, Piegza J, Dyrbus K, Hawranek M, SzygulaJurkiewicz B, Honisz G, Kalarus Z, Polonski L. Source: Kardiologia Polska. 2003 June; 58(6): 438-48; Discussion 448. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556010&dopt=Abstract

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New technique for superior guiding catheter support during advancement of a balloon in coronary angioplasty: the anchor technique. Author(s): Fujita S, Tamai H, Kyo E, Kosuga K, Hata T, Okada M, Nakamura T, Tsuji T, Takeda S, Bin Hu F, Masunaga N, Motohara S, Uehata H. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 August; 59(4): 482-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891613&dopt=Abstract

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Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction. Author(s): Ikeda N, Yasu T, Kubo N, Hashimoto S, Tsuruya Y, Fujii M, Kawakami M, Saito M. Source: Heart (British Cardiac Society). 2004 February; 90(2): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14729792&dopt=Abstract

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No effect of highly dosed nitric oxide donor molsidomine on the angiographic restenosis rate after percutaneous coronary angioplasty: a randomized, placebo controlled, double-blind trial. Author(s): Wohrle J, Hoher M, Nusser T, Hombach V, Kochs M. Source: The Canadian Journal of Cardiology. 2003 April; 19(5): 495-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717484&dopt=Abstract

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One-year survival in patients with acute myocardial infarction and a saphenous vein graft culprit treated with primary angioplasty. Author(s): Nguyen TT, O'Neill WW, Grines CL, Stone GW, Brodie BR, Cox DA, Grines LL, Boura JA, Dixon SR. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1250-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745114&dopt=Abstract

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Out of balance: a role of impaired superoxide dismutase activity for vascular constrictive remodeling after angioplasty. Author(s): Brandes RP. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 December; 23(12): 2121-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672879&dopt=Abstract

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Outcome of carotid stent-assisted angioplasty versus open surgical repair of recurrent carotid stenosis. Author(s): Bowser AN, Bandyk DF, Evans A, Novotney M, Leo F, Back MR, Johnson BL, Shames ML. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 September; 38(3): 432-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947248&dopt=Abstract

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91

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Outcome of primary angioplasty for acute myocardial infarction during routine duty hours versus during off-hours. Author(s): Henriques JP, Haasdijk AP, Zijlstra F; Zwolle Myocardial Infarction Study Group. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2138-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821237&dopt=Abstract

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Outcomes of bail-out stenting for suboptimal balloon angioplasty during primary intervention in acute myocardial infarction (The CADILLAC trial). Author(s): Ashby DT, Aymong EA, Grines CL, Cox DA, Garcia E, Mehran R, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Carroll JD, Turco M, Lansky AJ, Stone GW; CADILLAC trial. Source: The American Journal of Cardiology. 2003 November 1; 92(9): 1095-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583363&dopt=Abstract

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Outcomes of optimal or “stent-like”balloon angioplasty in acutemyocardial infarction: the CADILLAC trial. Author(s): Cox DA, Stone GW, Grines CL, Stuckey T, Cohen DJ, Tcheng JE, Garcia E, Guagliumi G, Iwaoka RS, Fahy M, Turco M, Lansky AJ, Griffin JJ, Mehran R; CADILLAC Investigators. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 971-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678914&dopt=Abstract

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Outcomes of primary coronary angioplasty and angioplasty after initial thrombolysis in the treatment of 374 consecutive patients with acute myocardial infarction. Author(s): Polonski L, Gasior M, Wasilewski J, Wilczek K, Wnek A, Adamowicz-Czoch E, Sikora J, Lekston A, Zebik T, Gierlotka M, Wojnar R, Szkodzinski J, Kondys M, Szygula-Jurkiewicz B, Wolk R, Zembala M. Source: American Heart Journal. 2003 May; 145(5): 855-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766744&dopt=Abstract

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Parameters of left ventricular diastolic function 48 hours after coronary angioplasty and stent implantation. Author(s): Schannwell CM, Schneppenheim M, Plehn G, Strauer BE. Source: J Invasive Cardiol. 2003 June; 15(6): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777672&dopt=Abstract

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Patency of Wallstents placed at the venous anastomosis of dialysis grafts for salvage of angioplasty-induced rupture. Author(s): Rajan DK, Clark TW. Source: Cardiovascular and Interventional Radiology. 2003 May-June; 26(3): 242-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562971&dopt=Abstract

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Patients with acute MI should be transferred for angioplasty. Author(s): Fitzsimmons A, Lindbloom EJ. Source: The Journal of Family Practice. 2003 December; 52(12): 940-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14653979&dopt=Abstract

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Percutaneous angioplasty and stenting of left subclavian artery stenosis in patients with left internal mammary-coronary bypass grafts: clinical experience and long-term follow-up. Author(s): Angle JF, Matsumoto AH, McGraw JK, Spinosa DJ, Hagspiel KD, Leung DA, Tribble CG. Source: Vascular and Endovascular Surgery. 2003 March-April; 37(2): 89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669139&dopt=Abstract

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Percutaneous balloon angioplasty for the treatment of iliofemoral arterial stenosis resulting from hyperhomocysteinemia in a child. Author(s): Maynar M, Lopez-Benitez R, Kirsch DS, Gomez-Sirvent J, Zerolo-Saez I, Qian Z. Source: Pediatric Radiology. 2003 August; 33(8): 546-50. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743659&dopt=Abstract

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Percutaneous balloon angioplasty of membranous obstruction of the inferior vena cava. Author(s): Mishra TK, Routray SN, Behera M, Patnaik UK, Satapathy C. Source: Indian Heart J. 2003 July-August; 55(4): 362-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14686667&dopt=Abstract

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Percutaneous internal carotid artery angioplasty with stenting: early and long-term results. Author(s): Dabrowski M, Bielecki D, Golebiewski P, Kwiecinski H. Source: Kardiologia Polska. 2003 June; 58(6): 469-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556013&dopt=Abstract

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Percutaneous transluminal angioplasty and stent placement for subclavian steal syndrome with concomitant anterograde flow in the left internal mammary artery graft for coronary artery bypass--case report. Author(s): Nishio A, Takami T, Ichinose T, Masamura S, Hara M, Shimada K, Kamimori K, Narikawa T. Source: Neurol Med Chir (Tokyo). 2003 October; 43(10): 488-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14620200&dopt=Abstract

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93

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Percutaneous transluminal angioplasty in the treatment of critical limb ischemia. Author(s): Molloy KJ, Nasim A, London NJ, Naylor AR, Bell PR, Fishwick G, Bolia A, Thompson MM. Source: Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. 2003 April; 10(2): 298-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877613&dopt=Abstract

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Percutaneous transluminal angioplasty of malfunctioning Brescia-Cimino arteriovenous fistula: analysis of factors adversely affecting long-term patency. Author(s): Sugimoto K, Higashino T, Kuwata Y, Imanaka K, Hirota S, Sugimura K. Source: European Radiology. 2003 July; 13(7): 1615-9. Epub 2002 November 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835976&dopt=Abstract

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Percutaneous transluminal coronary angioplasty for anastomotic stenosis after coronary arterial bypass grafting in Kawasaki disease. Author(s): Miyazaki A, Tsuda E, Miyazaki S, Kitamura S, Tomita H, Echigo S. Source: Cardiology in the Young. 2003 June; 13(3): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903877&dopt=Abstract

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Percutaneous transluminal coronary angioplasty in a patient with myocardial infarction after penetrating trauma. Author(s): O'Neill PA, Sinert RH, Sian KU, Kwan TW. Source: The Journal of Trauma. 2003 May; 54(5): 1000-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777917&dopt=Abstract

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Percutaneous transluminal renal angioplasty (PTRA) and surgical revascularisation in renovascular disease--a retrospective comparison of results, complications, and mortality. Author(s): Alhadad A, Ahle M, Ivancev K, Gottsater A, Lindblad B. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2004 February; 27(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14718896&dopt=Abstract

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Peroneal artery approach for angioplasty of the superficial femoral artery: a case report. Author(s): Wolosker N, Nakano L, Duarte FH, De Lucia N, Leao PP. Source: Vascular and Endovascular Surgery. 2003 March-April; 37(2): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669145&dopt=Abstract

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Angioplasty

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Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. Author(s): Granger CB, Mahaffey KW, Weaver WD, Theroux P, Hochman JS, Filloon TG, Rollins S, Todaro TG, Nicolau JC, Ruzyllo W, Armstrong PW; COMMA Investigators. Source: Circulation. 2003 September 9; 108(10): 1184-90. Epub 2003 August 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925454&dopt=Abstract

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Poor functional recovery may indicate restenosis in patients after coronary angioplasty. Author(s): Lan C, Chen SY, Chiu SF, Hsu CJ, Lai JS, Kuan PL. Source: Archives of Physical Medicine and Rehabilitation. 2003 July; 84(7): 1023-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881828&dopt=Abstract

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Postoperative infection associated with polyester patch angioplasty after carotid endarterectomy. Author(s): Rockman CB, Su WT, Domenig C, Lamparello PJ, Adelman MA, Jacobowitz GR, Pomposelli FB, Riles TS. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 August; 38(2): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891105&dopt=Abstract

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Postprocedural complications after angioplasty with stenting of the internal carotid artery. Author(s): Lu CJ, Kao HL, Sun Y, Liu HM, Jeng JS, Yip PK. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16(3): 308-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865625&dopt=Abstract

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Prediction of clinical response after renal angioplasty: respective value of renal Doppler sonography and scintigraphy. Author(s): Soulez G, Therasse E, Qanadli SD, Froment D, Leveille M, Nicolet V, Turpin S, Giroux MF, Guertin MC, Oliva VL. Source: Ajr. American Journal of Roentgenology. 2003 October; 181(4): 1029-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500224&dopt=Abstract

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Predictors of adverse long-term outcome in acute myocardial infarction patients undergoing primary percutaneous transluminal coronary angioplasty: with special reference to the admission concentration of lipoprotein (a). Author(s): Igarashi Y, Aizawa Y, Satoh T, Konno T, Ojima K, Aizawa Y. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 July; 67(7): 605-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845184&dopt=Abstract

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Predictors of improved renal function after percutaneous stent-supported angioplasty of severe atherosclerotic ostial renal artery stenosis. Author(s): Zeller T, Frank U, Muller C, Burgelin K, Sinn L, Bestehorn HP, Cook-Bruns N, Neumann FJ. Source: Circulation. 2003 November 4; 108(18): 2244-9. Epub 2003 October 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557357&dopt=Abstract

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Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty. Author(s): Cipollone F, Ferri C, Desideri G, Paloscia L, Materazzo G, Mascellanti M, Fazia M, Iezzi A, Cuccurullo C, Pini B, Bucci M, Santucci A, Cuccurullo F, Mezzetti A. Source: Circulation. 2003 December 2; 108(22): 2776-82. Epub 2003 November 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623801&dopt=Abstract

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Previous cytomegalovirus infection and restenosis after aggressive angioplasty with provisional stenting. Author(s): Mueller C, Hodgson JM, Bestehorn HP, Brutsche M, Perruchoud AP, Marsch S, Roskamm H, Buettner HJ. Source: Journal of Interventional Cardiology. 2003 August; 16(4): 307-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562670&dopt=Abstract

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Primary angioplasty for acute myocardial infarction--is it worth the wait? Author(s): Jacobs AK. Source: The New England Journal of Medicine. 2003 August 21; 349(8): 798-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930933&dopt=Abstract

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Primary angioplasty for ST-segment elevation myocardial infarction: ready for prime time? Author(s): Natarajan MK, Yusuf S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 July 8; 169(1): 32-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847037&dopt=Abstract

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Primary angioplasty in CADASIL. Author(s): Raghu C, Loubeyre C, Obadia E, Morice MC. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 June; 59(2): 235-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772249&dopt=Abstract

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Primary angioplasty or thrombolysis for acute myocardial infarction? Author(s): Massel D. Source: Lancet. 2003 March 15; 361(9361): 967; Author Reply 967-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648991&dopt=Abstract

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Primary angioplasty or thrombolysis for acute myocardial infarction? Author(s): Armstrong PW. Source: Lancet. 2003 March 15; 361(9361): 966-7; Author Reply 967-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648990&dopt=Abstract

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Primary angioplasty or thrombolysis for acute myocardial infarction? Author(s): Melandri G. Source: Lancet. 2003 March 15; 361(9361): 966; Author Reply 967-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648989&dopt=Abstract

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Primary angioplasty or thrombolysis for acute myocardial infarction? Author(s): Auer J, Berent R, Weber T, Eber B. Source: Lancet. 2003 March 15; 361(9361): 965-6; Author Reply 967-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648988&dopt=Abstract

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Primary angioplasty versus intravenous thrombolysis for acute myocardial infarction. Author(s): Cucherat M, Bonnefoy E, Tremeau G. Source: Cochrane Database Syst Rev. 2003; (3): Cd001560. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917910&dopt=Abstract

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Primary angioplasty with routine stenting compared with thrombolytic therapy in elderly patients with acute myocardial infarction. Author(s): Goldenberg I, Matetzky S, Halkin A, Roth A, Di Segni E, Freimark D, Elian D, Agranat O, Har Zahav Y, Guetta V, Hod H. Source: American Heart Journal. 2003 May; 145(5): 862-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766745&dopt=Abstract

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Primary angioplasty, instead of thrombolysis, for all patients with acute ST-elevation myocardial infarction? Author(s): Steffenino G, Dellavalle A, La Scala E, Baralis G. Source: Ital Heart J. 2003 April; 4(4): 219-24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784772&dopt=Abstract

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Primary coronary angioplasty versus thrombolysis for acute myocardial infarction. Author(s): Buchan I, Hooper L, McElduff P, Freemantle N, Martin D. Source: Lancet. 2003 April 12; 361(9365): 1304; Author Reply 1304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699991&dopt=Abstract

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Primary coronary angioplasty versus thrombolysis for acute myocardial infarction. Author(s): Fresco C. Source: Lancet. 2003 April 12; 361(9365): 1303; Author Reply 1304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699989&dopt=Abstract

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Primary coronary angioplasty versus thrombolysis for acute myocardial infarction. Author(s): French JK, Canborn TA, Sleeper LA. Source: Lancet. 2003 April 12; 361(9365): 1303-4; Author Reply 1304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699988&dopt=Abstract

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Primary coronary angioplasty with stenting for acute coronary syndrome in patients with isolated single coronary artery: a report of 2 cases. Author(s): Ohta H, Sumiyoshi M, Suwa S, Tamura H, Sasaki A, Kojima T, Mineda Y, Kojima S, Nakata Y. Source: Japanese Heart Journal. 2003 September; 44(5): 759-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587657&dopt=Abstract

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Primary percutaneous transluminal coronary angioplasty accelerates early myocardial reperfusion compared to thrombolytic therapy in patients with acute myocardial infarction. Author(s): Zeymer U, Schroder R, Machnig T, Neuhaus KL. Source: American Heart Journal. 2003 October; 146(4): 686-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564324&dopt=Abstract

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Primary percutaneous transluminal coronary angioplasty in the acute infarction of the right ventricle. Author(s): Gligic B, Orozovic V, Obradovic S, Rusovic S, Kostic J, Baskot B, Dincic D, Ristic-Andelkov A. Source: Vojnosanit Pregl. 2003 January-February; 60(1): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688116&dopt=Abstract

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Primary utilization of stents in angioplasty of superficial femoral artery. Author(s): Wolosker N, Nakano L, Anacleto MM, Puech-Leao P. Source: Vascular and Endovascular Surgery. 2003 July-August; 37(4): 271-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894369&dopt=Abstract

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Promising efficacy of primary gradual and prolonged balloon angioplasty in small coronary arteries: a randomized comparison with cutting balloon angioplasty and conventional balloon angioplasty. Author(s): Umeda H, Iwase M, Kanda H, Izawa H, Nagata K, Ishiki R, Sawada K, Murohara T, Yokota M. Source: American Heart Journal. 2004 January; 147(1): E4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14691442&dopt=Abstract

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Prospective evaluation of hydroperoxide plasma levels and stable nitric oxide end products in patients subjected to angioplasty for coronary artery disease. Author(s): Wykretowicz A, Dziarmaga M, Szczepanik A, Guzik P, Wysocki H. Source: International Journal of Cardiology. 2003 June; 89(2-3): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767540&dopt=Abstract

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Prothrombotic response to coronary angioplasty in patients with unstable angina and raised C-reactive protein. Author(s): Sciahbasi A, Andreotti F, De Cristofaro R, Fischetti D, Leone AM, Schiavoni G, Maseri A, Landolfi R. Source: Journal of Thrombosis and Thrombolysis. 2002 October; 14(2): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714832&dopt=Abstract

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Pulmonary balloon angioplasty of chronic thromboembolic pulmonary hypertension (CTEPH) in surgically inaccessible cases. Author(s): Pitton MB, Herber S, Mayer E, Thelen M. Source: Rofo. Fortschritte Auf Dem Gebiete Der Rontgenstrahlen Und Der Neuen Bildgebenden Verfahren. 2003 May; 175(5): 631-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743854&dopt=Abstract

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Quality improvement guidelines for the performance of cervical carotid angioplasty and stent placement. Author(s): Barr JD, Connors JJ 3rd, Sacks D, Wojak JC, Becker GJ, Cardella JF, Chopko B, Dion JE, Fox AJ, Higashida RT, Hurst RW, Lewis CA, Matalon TA, Nesbit GM, Pollock JA, Russell EJ, Seidenwurm DJ, Wallace RC; SIR Standards of Practice Committees. Source: Ajnr. American Journal of Neuroradiology. 2003 November-December; 24(10): 2020-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625227&dopt=Abstract

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Quality improvement guidelines for the performance of cervical carotid angioplasty and stent placement. Developed by a collaborative panel of the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, and the Society of Interventional Radiology. Author(s): Barr JD, Connors JJ 3rd, Sacks D, Wojak JC, Becker GJ, Cardella JF, Chopko B, Dion JE, Fox AJ, Higashida RT, Hurst RW, Lewis CA, Matalon TA, Nesbit GM, Pollock JA, Russell EJ, Seidenwurm DJ, Wallace RC; American Society of Interventional and Therapeutic Neuroradiology; American Society of Neuroradiology; Society of Interventional Radiology. Source: Journal of Vascular and Interventional Radiology : Jvir. 2003 September; 14(9 Pt 1): 1079-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514797&dopt=Abstract

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Randomized comparison between stenting and off-pump bypass surgery in patients referred for angioplasty. Author(s): Eefting F, Nathoe H, van Dijk D, Jansen E, Lahpor J, Stella P, Suyker W, Diephuis J, Suryapranata H, Ernst S, Borst C, Buskens E, Grobbee D, de Jaegere P. Source: Circulation. 2003 December 9; 108(23): 2870-6. Epub 2003 Dec 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14656913&dopt=Abstract

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Randomized comparison of percutaneous transluminal coronary angioplasty and medical therapy in stable survivors of acute myocardial infarction with single vessel disease: a study of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte. Author(s): Zeymer U, Uebis R, Vogt A, Glunz HG, Vohringer HF, Harmjanz D, Neuhaus KL; ALKK-Study Group. Source: Circulation. 2003 September 16; 108(11): 1324-8. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939210&dopt=Abstract

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Randomized trial of Rotational Atherectomy Versus Balloon Angioplasty for Diffuse In-stent Restenosis (ROSTER). Author(s): Sharma SK, Kini A, Mehran R, Lansky A, Kobayashi Y, Marmur JD. Source: American Heart Journal. 2004 January; 147(1): 16-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14691413&dopt=Abstract

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Real-time assessment of myocardial perfusion during balloon angioplasty of the left anterior descending coronary artery. Author(s): Main ML, Magalski A, Kusnetzky LL, Coen MM, Skolnick DG, Good TH. Source: The American Journal of Cardiology. 2003 September 15; 92(6): 656-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972101&dopt=Abstract

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Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. Author(s): Moons AH, Peters RJ, Bijsterveld NR, Piek JJ, Prins MH, Vlasuk GP, Rote WE, Buller HR. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821239&dopt=Abstract

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Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty. Author(s): Wohrle J, Grebe OC, Nusser T, Al-Khayer E, Schaible S, Kochs M, Hombach V, Hoher M. Source: Circulation. 2003 April 15; 107(14): 1840-3. Epub 2003 Apr 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682003&dopt=Abstract

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Regarding “Postoperative infection associated with polyester patch angioplasty after carotid endarterectomy”. Author(s): Chang JB, Stein TA. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 December; 38(6): 1445; Author Reply 1445. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14686406&dopt=Abstract

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Relation of ischemia-modified albumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced myocardial ischemia. Author(s): Quiles J, Roy D, Gaze D, Garrido IP, Avanzas P, Sinha M, Kaski JC. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 322-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888145&dopt=Abstract

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Relation of local platelet glycoprotein IIb/IIIa independent activation during coronary angioplasty in acute myocardial infarction to recovery of left ventricular function. Author(s): Taylor AJ, Bobik A, Berndt MC, Kalff V, Michaelides A, Jennings GL. Source: The American Journal of Cardiology. 2003 August 15; 92(4): 446-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914877&dopt=Abstract

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Relation of mortality of primary angioplasty during acute myocardial infarction to door-to-Thrombolysis In Myocardial Infarction (TIMI) time. Author(s): Juliard JM, Feldman LJ, Golmard JL, Himbert D, Benamer H, Haghighat T, Karila-Cohen D, Aubry P, Vahanian A, Steg PG. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1401-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804723&dopt=Abstract

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Renal angioplasty and stenting with distal protection of the main renal artery in ischemic nephropathy: early experience. Author(s): Holden A, Hill A. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 November; 38(5): 962-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14603201&dopt=Abstract

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Restenosis after carotid angioplasty and stenting: a follow-up study with duplex ultrasonography. Author(s): Christiaans MH, Ernst JM, Suttorp MJ, van den Berg JC, Overtoom TT, Kelder JC, Mauser HW, Ackerstaff RG; Antonius Carotid Endarterectomy, Angioplasty, and Stenting Study Group. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 August; 26(2): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917827&dopt=Abstract

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Retinopathy after percutaneous transluminal coronary angioplasty and stent insertion for acute myocardial infarction. Author(s): Kusano Y, Endo S, Mukai S, Yamaguchi T. Source: American Journal of Ophthalmology. 2003 September; 136(3): 557-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967820&dopt=Abstract

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Retrograde left ventricular hemodynamic assessment across bileaflet prosthetic aortic valves: the use of a high-fidelity pressure sensor angioplasty guidewire. Author(s): Parham W, El Shafei A, Rajjoub H, Ziaee A, Kern MJ. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 August; 59(4): 509-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891617&dopt=Abstract

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Retrograde vs. antegrade puncture for infra-inguinal angioplasty. Author(s): Nice C, Timmons G, Bartholemew P, Uberoi R. Source: Cardiovascular and Interventional Radiology. 2003 July-August; 26(4): 370-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667119&dopt=Abstract

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Role of cardiac troponin testing in percutaneous transluminal coronary angioplasty. Author(s): Davis GK. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2003; 63(3): 16774. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817902&dopt=Abstract

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Ruptured pseudo-aneurysm of the popliteal artery after percutaneous transluminal angioplasty. Author(s): Derom A. Source: Acta Chir Belg. 2003 February; 103(1): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658887&dopt=Abstract

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Safety and efficacy of sirolimus in kidney transplant patients and in patients with coronary artery disease undergoing angioplasty. Author(s): Tedesco Silva H Jr, Felipe CR, Machado PG, Garcia R, Motegi S, Hosaka BH, Hanzawa NM, Park SI, Casarini D, Lima VC, Franco M, Medina-Pestana JO. Source: Transplantation Proceedings. 2003 May; 35(3 Suppl): 177S-180S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742493&dopt=Abstract

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Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Author(s): Hedman M, Hartikainen J, Syvanne M, Stjernvall J, Hedman A, Kivela A, Vanninen E, Mussalo H, Kauppila E, Simula S, Narvanen O, Rantala A, Peuhkurinen K, Nieminen MS, Laakso M, Yla-Herttuala S. Source: Circulation. 2003 June 3; 107(21): 2677-83. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742981&dopt=Abstract

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Safety, efficacy, and cost advantages of combined coronary angiography and angioplasty. Author(s): Le Feuvre C, Helft G, Beygui F, Zerah T, Fonseca E, Catuli D, Batisse JP, Metzger JP. Source: Journal of Interventional Cardiology. 2003 June; 16(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800396&dopt=Abstract

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Safety, feasibility and efficacy of transradial primary angioplasty in patients with acute myocardial infarction. Author(s): Valsecchi O, Musumeci G, Vassileva A, Tespili M, Guagliumi G, Gavazzi A, Ferrazzi P. Source: Ital Heart J. 2003 May; 4(5): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848090&dopt=Abstract

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Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. Author(s): Henderson RA, Pocock SJ, Clayton TC, Knight R, Fox KA, Julian DG, Chamberlain DA; Second Randomized Intervention Treatment of Angina (RITA-2) Trial Participants. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1161-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522473&dopt=Abstract

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Severe aortic coarctation in infants less than 3 months: successful palliation by balloon angioplasty. Author(s): Rao PS, Jureidini SB, Balfour IC, Singh GK, Chen SC. Source: J Invasive Cardiol. 2003 April; 15(4): 202-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668848&dopt=Abstract

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Side branch protection with hydrophilic polymer coated guide wire during cutting balloon angioplasty of a bifurcated lesion. Author(s): Oyama N, Urasawa K, Sakai H, Kitabatake A. Source: Japanese Heart Journal. 2003 July; 44(4): 565-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906038&dopt=Abstract

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Simultaneous modeling of abciximab plasma concentrations and ex vivo pharmacodynamics in patients undergoing coronary angioplasty. Author(s): Mager DE, Mascelli MA, Kleiman NS, Fitzgerald DJ, Abernethy DR. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 December; 307(3): 969-76. Epub 2003 October 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534354&dopt=Abstract

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Six hour ambulation after elective coronary angioplasty and stenting with 7F guiding catheters ald low dose heparin. Author(s): Tengiz I, Ercan E, Bozdemir H, Durmaz O, Gurgun C, Nalbantgil I. Source: Kardiologia Polska. 2003 February; 58(2): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504634&dopt=Abstract

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Small-vessel stents for intracranial angioplasty: in vitro comparison of different stent designs and sizes by using CT angiography. Author(s): Hahnel S, Trossbach M, Braun C, Heiland S, Knauth M, Sartor K, Hartmann M. Source: Ajnr. American Journal of Neuroradiology. 2003 September; 24(8): 1512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679261&dopt=Abstract

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ST segment elevation in leads V1 to V3 due to isolated right ventricular branch occlusion during primary right coronary angioplasty. Author(s): Acikel M, Yilmaz M, Bozkurt E, Gurlertop Y, Kose N. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 September; 60(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929099&dopt=Abstract

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Stent angioplasty of severe atherosclerotic ostial renal artery stenosis in patients with diabetes mellitus and nephrosclerosis. Author(s): Zeller T, Muller C, Frank U, Burgelin K, Horn B, Schwarzwalder U, CookBruns N, Neumann FJ. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 April; 58(4): 510-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652503&dopt=Abstract

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Stent-supported angioplasty correction of symptomatic critical carotid angulation. Author(s): Bates MC, Kyer PD, Kavasmaneck C, AbuRahma A, Crotty B. Source: W V Med J. 2003 January-February; 99(1): 22-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762212&dopt=Abstract

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Subintimal angioplasty as a treatment of femoropopliteal artery occlusions. Author(s): Laxdal E, Jenssen GL, Pedersen G, Aune S. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 June; 25(6): 578-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787703&dopt=Abstract

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Subintimal angioplasty of long superficial femoral artery occlusions. Author(s): Yilmaz S, Sindel T, Yegin A, Luleci E. Source: Journal of Vascular and Interventional Radiology : Jvir. 2003 August; 14(8): 9971010. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902557&dopt=Abstract

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Successful angioplasty of a superficial femoral artery stenosis caused by a suturemediated closure device. Author(s): Gemmete JJ, Dasika N, Forauer AR, Cho K, Williams DM. Source: Cardiovascular and Interventional Radiology. 2003 July-August; 26(4): 410-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667128&dopt=Abstract

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Successful local fibrinolytic treatment and balloon angioplasty in superior mesenteric arterial embolism: a case report and literature review. Author(s): Calin GA, Calin S, Ionescu R, Croitoru M, Diculescu M, Oproiu A. Source: Hepatogastroenterology. 2003 May-June; 50(51): 732-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828073&dopt=Abstract

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Successful percutaneous coronary angioplasty via a solitary coronary ostium in the aorta (single coronary artery). Author(s): Quintal R, Nguyen T, Glancy DL. Source: J Invasive Cardiol. 2003 August; 15(8): 446-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890875&dopt=Abstract

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Successful rotational atherectomy in the setting of extensive coronary dissection: a case of failed balloon angioplasty in a nondilatable calcified lesion complicated by balloon rupture and extensive dissection. Author(s): Pedersen WR, Goldenberg IF, Johnson RK, Mooney MR. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 July; 59(3): 329-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822151&dopt=Abstract

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Superficial femoral artery occlusion: nitinol stents achieve better flow and reduce the need for medications than balloon angioplasty alone. Author(s): Cho L, Roffi M, Mukherjee D, Bhatt DL, Bajzer C, Yadav JS. Source: J Invasive Cardiol. 2003 April; 15(4): 198-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668846&dopt=Abstract

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Symptom-onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty. Author(s): De Luca G, Suryapranata H, Zijlstra F, van't Hof AW, Hoorntje JC, Gosselink AT, Dambrink JH, de Boer MJ; ZWOLLE Myocardial Infarction Study Group. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 991-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678918&dopt=Abstract

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Taking it to heart. Availability of emergency angioplasty could be key to best outcomes for heart attack patients--but offering the service might not be so healthy for a hospital's finances. Author(s): Becker C. Source: Modern Healthcare. 2004 January 12; 34(2): 28-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14959636&dopt=Abstract

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Ten-year outcome after saphenous vein patch angioplasty in males and females after carotid endarterectomy. Author(s): Chang JB, Stein TA. Source: Vascular and Endovascular Surgery. 2002 January-February; 36(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704521&dopt=Abstract

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The current practice of percutaneous transluminal coronary angioplasty (PTCA) and stent deployment and their long-term results in unstable and stable angina. Author(s): Raju BS, Rao NK. Source: J Indian Med Assoc. 2003 February; 101(2): 66-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841485&dopt=Abstract

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The effect of peripheral percutaneous transluminal angioplasty on quality of life in patients with intermittent claudication. Author(s): Cassar K, Bachoo P, Brittenden J. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 August; 26(2): 130-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917825&dopt=Abstract

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The efficacy of percutaneous transluminal angioplasty in the treatment of infrainguinal vein bypass graft stenosis. Author(s): Alexander JQ, Katz SG. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 May; 138(5): 510-3; Discussion 513. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742954&dopt=Abstract

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The impact of cutting balloon angioplasty for the treatment of diffuse in-stent restenosis. Author(s): Iijima R, Ikari Y, Anzai H, Nishida T, Tsunoda T, Nakamura M, Hara K, Yamaguchi T. Source: J Invasive Cardiol. 2003 August; 15(8): 427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890868&dopt=Abstract

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The incidence, predictors, and outcomes of early reinfarction after primary angioplasty for acute myocardial infarction. Author(s): Kernis SJ, Harjai KJ, Stone GW, Grines LL, Boura JA, Yerkey MW, O'Neill W, Grines CL. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522475&dopt=Abstract

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The obsession with primary angioplasty. Author(s): Melandri G. Source: Circulation. 2003 December 9; 108(23): E162. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662697&dopt=Abstract

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The prognostic importance of heart failure and age in patients treated with primary angioplasty. Author(s): Henriques JP, Zijlstra F, de Boer MJ, van't Hof AW, Gosselink AT, Dambrink JH, Suryapranata H, Hoorntje JC. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 June; 5(3): 291-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798826&dopt=Abstract

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Tibioperoneal angioplasty and bypass. Author(s): Baird RN, Bradley MD, Murphy KP. Source: Acta Chir Belg. 2003 August; 103(4): 383-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14524156&dopt=Abstract

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Time delays negate advantage of primary balloon angioplasty over fibrinolytic therapy in heart attack treatment. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 October 31; 14(21): 1, 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14628763&dopt=Abstract

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Timely lessons in heart attack management. Heart attack patients may benefit more from angioplasty than clot-busting drugs, even if it means waiting two hours. Author(s): Ornato JP. Source: Health News. 2003 October; 9(10): 8-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14619769&dopt=Abstract

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Total plasma homocysteine and restenosis after percutaneous coronary angioplasty: current evidence. Author(s): Schnyder G, Rouvinez G. Source: Annals of Medicine. 2003; 35(3): 156-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822737&dopt=Abstract

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Transbrachial insertion of an intra-aortic balloon pump for complex coronary angioplasty. Author(s): Noel BM, Gleeton O, Barbeau GR. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 September; 60(1): 36-9; Discussion 40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929100&dopt=Abstract

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Transcatheter angioplasty for acquired pulmonary vein stenosis after radiofrequency ablation. Author(s): Qureshi AM, Prieto LR, Latson LA, Lane GK, Mesia CI, Radvansky P, White RD, Marrouche NF, Saad EB, Bash DL, Natale A, Rhodes JF. Source: Circulation. 2003 September 16; 108(11): 1336-42. Epub 2003 Sep 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952852&dopt=Abstract

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Transesophageal echocardiography evaluation and follow-up of left main coronary artery patch angioplasty. Author(s): Sharoni E, Erez E, Shapira Y, Vidne BA, Sagie A. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 April; 23(4): 585-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694780&dopt=Abstract

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Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Author(s): Dalby M, Bouzamondo A, Lechat P, Montalescot G. Source: Circulation. 2003 October 14; 108(15): 1809-14. Epub 2003 Oct 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530206&dopt=Abstract

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Transluminal angioplasty in a patient with a single coronary artery during the acute phase of a myocardial infarction. Author(s): Boulet V, Lipiecki J, Philippot F, Durel N, De Tauriac O, Amonchot A, Citron B, Ponsonnaille J. Source: Journal of Interventional Cardiology. 2003 October; 16(5): 371-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14603792&dopt=Abstract

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Transluminal balloon angioplasty improves brain tissue oxygenation and metabolism in severe vasospasm after aneurysmal subarachnoid hemorrhage: case report. Author(s): Hoelper BM, Hofmann E, Sporleder R, Soldner F, Behr R. Source: Neurosurgery. 2003 April; 52(4): 970-4; Discussion 974-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657196&dopt=Abstract

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Treatment of acute intracranial vertebrobasilar dissection with angioplasty and stent placement: report of two cases. Author(s): Willing SJ, Skidmore F, Donaldson J, Nobo UL, Chernukha K. Source: Ajnr. American Journal of Neuroradiology. 2003 May; 24(5): 985-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748108&dopt=Abstract

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Treatment of in-stent restenosis with excimer laser coronary angioplasty. Author(s): Karaca I, Ilkay E, Akbulut M, Yavuzkir M. Source: Japanese Heart Journal. 2003 March; 44(2): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718480&dopt=Abstract

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Treatment of subclavian steal syndrome with percutaneous transluminal angioplasty and stenting: case report. Author(s): Fregni F, Castelo-Branco LE, Conforto AB, Yamamoto FI, Campos CR, Puglia P Jr, Caldas JG, Scaff M. Source: Arquivos De Neuro-Psiquiatria. 2003 March; 61(1): 95-9. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715028&dopt=Abstract

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Use of intravenous abciximab as adjunctive therapy for carotid angioplasty and stent placement. Author(s): Arab D, Yahia AM, Qureshi AI. Source: International Journal of Cardiovascular Interventions. 2003; 5(2): 61-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745860&dopt=Abstract

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Usefulness of circulating interleukin-18 concentration in acute myocardial infarction as a risk factor for late restenosis after emergency coronary angioplasty. Author(s): Kawasaki D, Tsujino T, Morimoto S, Fujioka Y, Naito Y, Okumura T, Masutani M, Shimizu H, Yuba M, Ueda A, Ohyanagi M, Kashiwamura S, Okamura H, Iwasaki T. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1258-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745116&dopt=Abstract

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Usefulness of creatinine clearance in predicting early and late death after primary angioplasty for acute myocardial infarction. Author(s): Dixon SR, O'Neill WW, Sadeghi HM, Stone GW, Brodie B, Cox DA, Garcia E, Mattos L, Grines LL, Boura JA, Morice MC, Grines CL. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1454-7, A6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804732&dopt=Abstract

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Usefulness of myocardial blush grade early and late after primary coronary angioplasty for acute myocardial infarction in predicting left ventricular function. Author(s): Hoffmann R, Haager P, Arning J, Christott P, Radke P, Blindt R, Ortlepp J, Lepper W, Hanrath P. Source: The American Journal of Cardiology. 2003 November 1; 92(9): 1015-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583349&dopt=Abstract

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Variation in hospital length of stay in patients with acute myocardial infarction undergoing primary angioplasty and the need to change the diagnostic-related group system. Author(s): Bartholomew BA, Harjai KJ, Grines CL, Boura JA, Grines LL, Stone GW, Cox DA, Brodie BR, O'Neill WW. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 830-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516886&dopt=Abstract

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Vertebral angioplasty for treatment of transient monocular blindness. Author(s): Rutgers DR, de Kort GA, Lo TH, Kappelle LJ. Source: Journal of Neurology. 2003 April; 250(4): 501-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760389&dopt=Abstract

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Vertebral artery origin angioplasty and primary stenting: safety and restenosis rates in a prospective series. Author(s): Cloud GC, Crawley F, Clifton A, McCabe DJ, Brown MM, Markus HS. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 586-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700299&dopt=Abstract

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Vertigo secondary to isolated PICA insufficiency: successful treatment with balloon angioplasty. Author(s): Koenigsberg RA, McCormick D, Thomas C, Yee M, Williams N. Source: Surgical Neurology. 2003 October; 60(4): 306-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505846&dopt=Abstract

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Veterans' system-of-care preferences for percutaneous transluminal coronary angioplasty in a rural setting. Author(s): Weeks WB, O'Rourke DJ, Ryder LB, Straw MM. Source: The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association. 2003 Spring; 19(2): 105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696845&dopt=Abstract

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

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

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

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

A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial. Author(s): Thoraxcenter, Erasmus University Hospital, Rotterdam, The Netherlands. Source: Serruys, P W Foley, D P Jackson, G Bonnier, H Macaya, C Vrolix, M Branzi, A Shepherd, J Suryapranata, H de Feyter, P J Melkert, R van Es, G A Pfister, P J Eur-HeartJ. 1999 January; 20(1): 58-69 0195-668X

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Aggressive management of aneurysmal subarachnoid haemorrhage based on a papaverine angioplasty protocol. Author(s): North and West Cerebrovascular Unit, Department of Surgery, The University of Sydney, Australia. Source: Morgan, M K Jonker, B Finfer, S Harrington, T Dorsch, N W J-Clin-Neurosci. 2000 July; 7(4): 305-8 0967-5868

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Angiography for renal artery stenosis: no additional impairment of renal function by angioplasty. Author(s): Abteilung Nephrologie, Medizinische Hochschule Hannover, Germany. [email protected] Source: Lufft, VolkMarch Hoogestraat Lufft, Linda Fels, Luder M Egbeyong Baiyee, Daniel Olbricht, Christoph J Galanski, Michael Eur-Radiol. 2002 April; 12(4): 804-9 09387994

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Ask the doctors. Is it a good idea to take folate if you have had an angioplasty? Source: Anonymous Heart-Advis. 2003 January; 6(1): 8 1523-9004

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Clinical evaluation of the effect of percutaneous transluminal angioplasty and intraarterial papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage. Author(s): Department of Neurosurgery, National Defense Medical College, Saitama, Japan. Source: Katoh, H Shima, K Shimizu, A Takiguchi, H Miyazawa, T Umezawa, H Nawashiro, H Ishihara, S Kaji, T Makita, K Tsuchiya, K Neurol-Res. 1999 March; 21(2): 195-203 0161-6412

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Clinical trials of IIb/IIIa receptor blockers in patients undergoing angioplasty. Author(s): Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, BT12 6BA, N. Ireland. Source: Mathew, T P Adgey, A A Semin-Interv-Cardiol. 1999 June; 4(2): 67-75 1084-2764

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Cognitive appraisal and cardiac risk reduction behavior following coronary angioplasty. Author(s): Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA., USA. Source: Kimble, L P West-J-Nurs-Res. 1998 December; 20(6): 733-44 0193-9459

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Combined use of Orgaran and Reopro during coronary angioplasty in patients unable to receive heparin. Author(s): Department of Internal Medicine, St. Michael's Hospital, Toronto, Ontario, Canada. Source: Cantor, W J Leblanc, K Garvey, B Watson, K R Rasymas, A Strauss, B H Catheter-Cardiovasc-Intervolume 1999 March; 46(3): 352-5 1522-1946

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Comparison of balloon angioplasty and papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage. Author(s): Department of Neurological Surgery, University of Washington School of Medicine, Harborview Medical Center, Seattle 98104, USA. Source: Elliott, J P Newell, D W Lam, D J Eskridge, J M Douville, C M Le Roux, P D Lewis, D H Mayberg, M R Grady, M S Winn, H R J-Neurosurg. 1998 February; 88(2): 277-84 0022-3085

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Costs and effectiveness of using coumarins before, during and after coronary angioplasty. Author(s): Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands. [email protected] Source: ten Berg, J M Kelder, J C Plokker, T H van Hout, B A Pharmacoeconomics. 2002; 20(12): 847-53 1170-7690

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Current indications and results of cerebral angioplasty. Author(s): Department of Neurological Surgery, University of Washington, Seattle, Washington, USA. Source: Newell, D W Eskridge, J M Aaslid, R Acta-Neurochir-Suppl. 2001; 77: 181-3 0065-1419

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Dosimetry of rhenium-188 diethylene triamine penta-acetic acid for endovascular intra-balloon brachytherapy after coronary angioplasty. Author(s): Department of Nuclear Medicine, Seoul National University College of Medicine, Korea. Source: Lee, J Lee, D S Kim, K M Yeo, J S Cheon, G J Kim, S K Ahn, J Y Jeong, J M Chung, J K Lee, M C Eur-J-Nucl-Med. 2000 January; 27(1): 76-82 0340-6997

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Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent--a pilot study in the setting of coronary angioplasty. Author(s): Hopital Universitaire Saint-Jacques, Besancon, France. Source: Vuillemenot, A Schiele, F Meneveau, N Claudel, S Donat, F Fontecave, S Cariou, R Samama, M M Bassand, J P Thromb-Haemost. 1999 February; 81(2): 214-20 0340-6245

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Efficacy of transluminal angioplasty for the management of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Author(s): Department of Neurosurgery, Louisiana State University Medical Center, Shreveport 71130, USA. [email protected] Source: Polin, R S Coenen, V A Hansen, C A Shin, P Baskaya, M K Nanda, A Kassell, N F J-Neurosurg. 2000 February; 92(2): 284-90 0022-3085

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Endovascular brachytherapy for the prevention of restenosis after angioplasty. Author(s): Department of Nuclear Medicine, University of Ulm, Germany. Source: Kotzerke, J Hanke, H Hoher, M Eur-J-Nucl-Med. 2000 February; 27(2): 223-36 0340-6997

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Evaluation of ischemia-reperfusion damage during coronary angioplasty. Electrocardiographic assessment and biochemical modifications in blood from the coronary sinus. Author(s): Institute of Biochemistry, University of Ancona, Italy. Source: Tomasetti, M Alleva, R Piva, R Pancrazi, A Solenghi, M D Mucaj, A Littarru, G P Ital-Heart-J. 2000 March; 1(3): 216-20 1129-471X

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Heparin and coumadin versus acetylsalicylic acid for prevention of restenosis after coronary angioplasty. Author(s): Swiss Cardiovascular Center, University Hospital, Bern, Switzerland.

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Source: Garachemani, Ali Reza Fleisch, Martin Windecker, Stephan Pfiffner, Dorothy Meier, Bernhard Catheter-Cardiovasc-Intervolume 2002 Mar; 55(3): 315-20 1522-1946 •

Integrative cardiac revitalization: bypass surgery, angioplasty, and chelation. Benefits, risks, and limitations. Author(s): University of California at Berkeley, USA. Source: Kidd, P M Altern-Med-Revolume 1998 February; 3(1): 4-17 1089-5159

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Leukocyte/endothelium activation and interactions during femoral percutaneous transluminal angioplasty. Author(s): Department of Internal Medicine, Ev. Hospital Konigin Elisabeth Herzberge, Herzbergstrasse 79, 10362 Berlin, Germany. Source: Ludemann, J Schulte, K L Hader, O Brehme, S Volk, H D Docke, W D Vasc-Surg. 2001 Jul-August; 35(4): 293-301 0042-2835

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Local administration of ramiprilat is less effective than oral ramipril in preventing restenosis after balloon angioplasty in an animal model. Author(s): Department of Diagnostic Radiology, Eberhard-Karls-University, Tubingen, Germany. Source: Kalinowski, M Tepe, G Schieber, A Brehme, U Bruck, B Erley, C M Claussen, C D Duda, S H J-Vasc-Interv-Radiol. 1999 Nov-December; 10(10): 1397-404 1051-0443

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Nicorandil enhances myocardial tolerance to ischemia without progressive collateral recruitment during coronary angioplasty. Author(s): The First Department of Internal Medicine, Hiroshima University School of Medicine, Japan. Source: Sakai, K Yamagata, T Teragawa, H Matsuura, H Chayama, K Circ-J. 2002 April; 66(4): 317-22 1346-9843

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Nicorandil, a hybrid between nitrate and ATP-sensitive potassium channel opener, preconditions human heart to ischemia during percutaneous transluminal coronary angioplasty. Author(s): Cardiovascular Division, Ishinkai Yao General Hospital, Osaka, Japan. Source: Yasuda, T Hashimura, K Matsu ura, Y Kato, Y Ueda, T Mori, I Kijima, Y JpnCirc-J. 2001 June; 65(6): 526-30 0047-1828

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Nicorandil-induced preconditioning as evidenced by troponin T measurements after coronary angioplasty in patients with stable angina pectoris. Author(s): First Department of Internal Medicine, Hiroshima University School of Medicine, Japan. Source: Sakai, K Yamagata, T Teragawa, H Matsuura, H Chayama, K Jpn-Heart-J. 2002 September; 43(5): 443-53 0021-4868

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Opening of K(ATP) channel attenuates the increase in QT dispersion produced by the first balloon inflation during coronary angioplasty. Author(s): Department of Cardiology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan. [email protected] Source: Ashikaga, T Nishizaki, M Arita, M Yamawake, N Fujii, H Kishi, Y Isobe, M Hiraoka, M Circ-J. 2002 May; 66(5): 469-72 1346-9843

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Percutaneous femoral artery angioplasty with stent-in-stent technique and tirofiban administration. Author(s): Department of Invasive Cardiology, Montevergine Clinic, Mercogliano, Italy. [email protected] Source: Ambrosini, V Battaglia, S Cioppa, A Lo Muzio, L Salemme, L Sorropago, G Tesoria, T Rubino, P J-Invasive-Cardiol. 2002 October; 14(10): 619-23 1042-3931

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Prevention of restenosis after coronary angioplasty: a pharmacological approach. Author(s): Cardiology Centre, University Hospital, Geneva, Switzerland. Source: Meier, B Eur-Heart-J. 1989 December; 10 Suppl G: 64-8 0195-668X

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Site-specific delivery of iloprost during experimental angioplasty suppresses smooth muscle cell proliferation. Author(s): Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Source: Kandarpa, K Nakatsuka, S Yousuf, N Barry, J J J-Vasc-Interv-Radiol. 1998 MayJune; 9(3): 487-93 1051-0443

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Stent-assisted angioplasty of intracranial vertebrobasilar atherosclerosis: an initial experience. Author(s): Department of Neurosurgery, Cleveland Clinic Foundation, Ohio 44195, USA. [email protected] Source: Rasmussen, P A Perl, J Barr, J D Markarian, G Z Katzan, I Sila, C Krieger, D Furlan, A J Masaryk, T J J-Neurosurg. 2000 May; 92(5): 771-8 0022-3085

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The optimal mode of coronary revascularization for diabetics. A risk-adjusted longterm study comparing coronary angioplasty and coronary bypass surgery. Author(s): Cardiovascular and Cardiothoracic Research Center, Mid America Heart Institute, Kansas City, Missouri, USA. Source: O'Keefe, J H Blackstone, E H Sergeant, P McCallister, B D Eur-Heart-J. 1998 November; 19(11): 1696-703 0195-668X

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Time course of free radical production after primary coronary angioplasty for acute myocardial infarction and the effect of vitamin C. Author(s): The Second Department of Internal Medicine, Hirosaki University School of Medicine, Japan. Source: Guan, W Osanai, T Kamada, T Ishizaka, H Hanada, H Okumura, K Jpn-Circ-J. 1999 December; 63(12): 924-8 0047-1828

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Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations. Author(s): Department of Neurosurgery, University of Mississippi Medical Center, Jackson 39216-4505, USA. Source: Zubkov, A Y Lewis, A I Scalzo, D Surg-Neurol. 1999 January; 51(1): 75-9; discussion 80 0090-3019

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Two-year results of a controlled study of residential rehabilitation for patients treated with percutaneous transluminal coronary angioplasty. A randomized study of a multifactorial programme. Author(s): Department of Cardiology, Thoracic Clinics, Karolinska Hospital, Stockholm, Sweden. Source: Hofman Bang, C Lisspers, J Nordlander, R Nygren, A Sundin, O Ohman, A Ryden, L Eur-Heart-J. 1999 October; 20(20): 1465-74 0195-668X

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

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

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

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

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

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to angioplasty; 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: •

Food and Diet The Dean Ornish Diet Source: Healthnotes, Inc.; www.healthnotes.com

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

A prescreening system for potential antiproliferative agents: implications for local treatment strategies of postangioplasty restenosis. Author(s): Voisard R, Seitzer U, Baur R, Dartsch PC, Osterhues H, Hoher M, Hombach V. Source: International Journal of Cardiology. 1995 August; 51(1): 15-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8522393&dopt=Abstract

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A salvianolic acid B-rich fraction of Salvia miltiorrhiza induces neointimal cell apoptosis in rabbit angioplasty model. Author(s): Hung HH, Chen YL, Lin SJ, Yang SP, Shih CC, Shiao MS, Chang CH. Source: Histology and Histopathology. 2001 January; 16(1): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11193193&dopt=Abstract

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Associations between different status of myocardial ischemia and ischemia-related negative or positive epicardial U-waves: observations during coronary angioplasty. Author(s): Kataoka H, Yano S. Source: Journal of Electrocardiology. 1999 October; 32(4): 293-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10549905&dopt=Abstract

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Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate? Author(s): Bellamy CM, Schofield PM, Faragher EB, Ramsdale DR. Source: European Heart Journal. 1992 December; 13(12): 1626-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1289091&dopt=Abstract

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Clinical experience of emergency coronary artery bypass grafting following failed percutaneous transluminal coronary angioplasty. Author(s): Kioka Y, Dallan L, Oliveira S, Jatene A. Source: Jpn J Surg. 1991 November; 21(6): 643-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1787610&dopt=Abstract

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Coronary angioplasty in the United States. Author(s): Jutzy KR. Source: Rev Port Cardiol. 1999 February; 18 Suppl 1: I37-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10191674&dopt=Abstract

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Correlations between preprocedure mood and clinical outcome in patients undergoing coronary angioplasty. Author(s): Grunberg GE, Crater SW, Green CL, Seskevich J, Lane JD, Koenig HG, Bashore TM, Morris KG, Mark DB, Krucoff MW. Source: Cardiology in Review. 2003 November-December; 11(6): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14580299&dopt=Abstract

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Desirability of immediate surgical standby for coronary angioplasty. Author(s): Levy RD, Bennett DH, Brooks NH. Source: British Heart Journal. 1991 February; 65(2): 68-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1867949&dopt=Abstract

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Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty. Author(s): Grigg LE, Kay TW, Valentine PA, Larkins R, Flower DJ, Manolas EG, O'Dea K, Sinclair AJ, Hopper JL, Hunt D. Source: Journal of the American College of Cardiology. 1989 March 1; 13(3): 665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2537349&dopt=Abstract

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Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism. Author(s): de Lorgeril M, Salen P. Source: Nutr Metab Cardiovasc Dis. 2003 December; 13(6): 345-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14979680&dopt=Abstract

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Do fish oils prevent restenosis after coronary angioplasty? Author(s): Leaf A, Jorgensen MB, Jacobs AK, Cote G, Schoenfeld DA, Scheer J, Weiner BH, Slack JD, Kellett MA, Raizner AE, et al. Source: Circulation. 1994 November; 90(5): 2248-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7955181&dopt=Abstract

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Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Author(s): Bairati I, Roy L, Meyer F. Source: Circulation. 1992 March; 85(3): 950-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1537131&dopt=Abstract

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Early and long-term outcome after emergency coronary artery bypass surgery after failed coronary angioplasty. Author(s): Buffet P, Danchin N, Villemot JP, Amrein D, Ethevenot G, Juilliere Y, Mathieu P, Cherrier F. Source: Circulation. 1991 November; 84(5 Suppl): Iii254-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1934417&dopt=Abstract

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Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. Author(s): Nye ER, Ablett MB, Robertson MC, Ilsley CD, Sutherland WH. Source: Aust N Z J Med. 1990 August; 20(4): 549-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2222347&dopt=Abstract

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Effect of high dose verapamil on restenosis after peripheral angioplasty. Author(s): Schweizer J, Kirch W, Koch R, Hellner G, Uhlmann K. Source: Journal of the American College of Cardiology. 1998 May; 31(6): 1299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9581724&dopt=Abstract

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Effect of the antioxidant Nicanartine on the proliferative and inflammatory response after experimental balloon angioplasty. Author(s): Wohlfrom M, Hanke S, Kamenz J, Voisard R, Heise N, Seibold W, Lenz C, Quack G, Wuhlfroth P, Hanke H. Source: Coronary Artery Disease. 1998; 9(12): 831-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9894928&dopt=Abstract

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Effect of vitamin E supplementation on circulating cell adhesion molecules pre- and post-coronary angioplasty. Author(s): Ferns GA, Forster LA, Williams JC, Tull SP, Verma PK, Starkey B, Gershlick AH. Source: Annals of Clinical Biochemistry. 2000 September; 37 ( Pt 5): 649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11026517&dopt=Abstract

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Effects of laser irradiation on human erythrocytes: considerations concerning clinical laser angioplasty. Author(s): Theis JH, Lee G, Ikeda RM, Stobbe D, Ogata C, Lui H, Mason DT. Source: Clin Cardiol. 1983 August; 6(8): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6616986&dopt=Abstract

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Emergency surgical revascularisation for coronary angioplasty complications. Author(s): Carey JA, Davies SW, Balcon R, Layton C, Magee P, Rothman MT, Timmis AD, Wright JE, Walesby RK. Source: British Heart Journal. 1994 November; 72(5): 428-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7818959&dopt=Abstract

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Experimental studies on prevention of atherosclerotic arterial stenosis and restenosis after angioplasty with Andrographis Paniculata Nees and fish oil. Author(s): Wang DW, Zhao HY. Source: J Tongji Med Univ. 1993; 13(4): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8151735&dopt=Abstract

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Fish oil supplements and restenosis after percutaneous transluminal coronary angioplasty. Author(s): Reis GJ, Pasternak RC. Source: The American Journal of Cardiology. 1990 August 1; 66(3): 385-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2368688&dopt=Abstract

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Fish oil supplements for prevention of restenosis after coronary angioplasty. Author(s): Kaul U, Sanghvi S, Bahl VK, Dev V, Wasir HS. Source: International Journal of Cardiology. 1992 April; 35(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1563884&dopt=Abstract

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Influence of catheter technology and adjuvant medication on acute complications in percutaneous coronary angioplasty. Author(s): Spielberg C, Schnitzer L, Linderer T, Schroder R. Source: Catheterization and Cardiovascular Diagnosis. 1990 October; 21(2): 72-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2225038&dopt=Abstract

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Inhibition of restenosis by beraprost sodium (a prostaglandin I2 analogue) in the atherosclerotic rabbit artery after angioplasty. Author(s): Isogaya M, Yamada N, Koike H, Ueno Y, Kumagai H, Ochi Y, Okazaki S, Nishio S. Source: Journal of Cardiovascular Pharmacology. 1995 June; 25(6): 947-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7564340&dopt=Abstract

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Integrative cardiac revitalization: bypass surgery, angioplasty, and chelation. Benefits, risks, and limitations. Author(s): Kidd PM. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1998 February; 3(1): 4-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9600022&dopt=Abstract

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Marine lipids and coronary angioplasty. Benefit or risk. Author(s): Sipperly ME. Source: Progress in Cardiovascular Nursing. 1989 October-December; 4(4): 119-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2690063&dopt=Abstract

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N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. Author(s): Johansen O, Brekke M, Seljeflot I, Abdelnoor M, Arnesen H. Source: Journal of the American College of Cardiology. 1999 May; 33(6): 1619-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10334433&dopt=Abstract

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Personal experience with “use of hypnosis before and during angioplasty”. Author(s): Kostka M. Source: Am J Clin Hypn. 1992 April; 34(4): 281-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1580234&dopt=Abstract

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Pilot findings of a percutaneous transluminal coronary angioplasty-restenosis-prone prevention program. Author(s): Goodman M. Source: Mayo Clinic Proceedings. 1997 May; 72(5): 487. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146696&dopt=Abstract

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Preventing restenosis with fish oils following coronary angioplasty. A meta-analysis. Author(s): Gapinski JP, VanRuiswyk JV, Heudebert GR, Schectman GS. Source: Archives of Internal Medicine. 1993 July 12; 153(13): 1595-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8323422&dopt=Abstract

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Prevention of atherosclerotic arterial stenosis and restenosis after angioplasty with Andrographis paniculata nees and fish oil. Experimental studies of effects and

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mechanisms. Author(s): Wang DW, Zhao HY. Source: Chinese Medical Journal. 1994 June; 107(6): 464-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7956489&dopt=Abstract •

Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis ITalian Study (ESPRIT). Author(s): Maresta A, Balduccelli M, Varani E, Marzilli M, Galli C, Heiman F, Lavezzari M, Stragliotto E, De Caterina R; ESPRIT Investigators. Source: American Heart Journal. 2002 June; 143(6): E5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075272&dopt=Abstract

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Prostanoid release immediately after balloon angioplasty in three models of atherosclerosis in rabbits. Author(s): Mattsson E, Brunkwall J, Falt K, Bergqvist D. Source: The European Journal of Surgery = Acta Chirurgica. 1993 January; 159(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8095801&dopt=Abstract

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Randomised trial of fish oil for prevention of restenosis after coronary angioplasty. Author(s): Reis GJ, Boucher TM, Sipperly ME, Silverman DI, McCabe CH, Baim DS, Sacks FM, Grossman W, Pasternak RC. Source: Lancet. 1989 July 22; 2(8656): 177-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2568519&dopt=Abstract

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Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. Author(s): Dehmer GJ, Popma JJ, van den Berg EK, Eichhorn EJ, Prewitt JB, Campbell WB, Jennings L, Willerson JT, Schmitz JM. Source: The New England Journal of Medicine. 1988 September 22; 319(12): 733-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2842680&dopt=Abstract

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Restenosis following coronary angioplasty: clinical presentations and therapeutic options. Author(s): Levine GN, Chodos AP, Loscalzo J. Source: Clin Cardiol. 1995 December; 18(12): 693-703. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8608668&dopt=Abstract

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Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin. Author(s): Braden GA, Knapp HR, FitzGerald GA. Source: Circulation. 1991 August; 84(2): 679-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1860212&dopt=Abstract

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Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. Author(s): Sollott SJ, Cheng L, Pauly RR, Jenkins GM, Monticone RE, Kuzuya M, Froehlich JP, Crow MT, Lakatta EG, Rowinsky EK, et al. Source: The Journal of Clinical Investigation. 1995 April; 95(4): 1869-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7706494&dopt=Abstract

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Tetradecylthioacetic acid reduces stenosis development after balloon angioplasty injury of rabbit iliac arteries. Author(s): Kuiper KK, Muna ZA, Erga KS, Dyroy E, Svendsen E, Berge RK, Nordrehaug JE. Source: Atherosclerosis. 2001 October; 158(2): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583704&dopt=Abstract

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The effect of a psychological intervention program on the risk of a new coronary event after angioplasty: a feasibility study. Author(s): Appels A, Bar F, Lasker J, Flamm U, Kop W. Source: Journal of Psychosomatic Research. 1997 August; 43(2): 209-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9278909&dopt=Abstract

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The Frankfurt experience in restenosis after coronary angioplasty. Author(s): Bussmann WD, Kaltenbach M, Kober G, Vallbracht C. Source: The American Journal of Cardiology. 1987 July 31; 60(3): 48B-49B. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2956842&dopt=Abstract

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The Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) trial. Results of a multicenter randomized trial investigating the effects of high dose unfractionated heparin on angiographic restenosis and clinical outcome. Author(s): Brack MJ, Ray S, Chauhan A, Fox J, Hubner PJ, Schofield P, Harley A, Gershlick AH. Source: Journal of the American College of Cardiology. 1995 October; 26(4): 947-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7560622&dopt=Abstract

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Use of hypnosis before and during angioplasty. Author(s): Weinstein EJ, Au PK. Source: Am J Clin Hypn. 1991 July; 34(1): 29-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1951141&dopt=Abstract

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Usefulness of fish oil supplements in preventing clinical evidence of restenosis after percutaneous transluminal coronary angioplasty. Author(s): Milner MR, Gallino RA, Leffingwell A, Pichard AD, Brooks-Robinson S, Rosenberg J, Little T, Lindsay J Jr.

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Source: The American Journal of Cardiology. 1989 August 1; 64(5): 294-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2526993&dopt=Abstract •

Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Author(s): DeMaio SJ, King SB 3rd, Lembo NJ, Roubin GS, Hearn JA, Bhagavan HN, Sgoutas DS. Source: Journal of the American College of Nutrition. 1992 February; 11(1): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1541798&dopt=Abstract

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Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty. Author(s): Orbe J, Rodriguez JA, Calvo A, Grau A, Belzunce MS, Martinez-Caro D, Paramo JA. Source: Cardiovascular Research. 2001 February 1; 49(2): 484-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164859&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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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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

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

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The following is a specific Web list relating to angioplasty; 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 Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Peripheral Vascular Disease Source: Healthnotes, Inc.; www.healthnotes.com Shock Source: Integrative Medicine Communications; www.drkoop.com TIAs Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com

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Alternative Therapy Chelation Therapy Source: Healthnotes, Inc.; www.healthnotes.com Chelation Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679,00.html

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Herbs and Supplements EDTA Source: Integrative Medicine Communications; www.drkoop.com Ethylenediaminetetraacetic Acid (EDTA) Source: Integrative Medicine Communications; www.drkoop.com

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON ANGIOPLASTY Overview In this chapter, we will give you a bibliography on recent dissertations relating to angioplasty. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “angioplasty” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on angioplasty, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Angioplasty ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to angioplasty. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A Study on the Cost Effectiveness of Percutaneous Transluminal Coronary Angioplasty (PTCA) and Coronary Artery Bypass Surgery (CABG) in Multivessel Artery Disease by Lee, Jae Sang, PhD from Emory University, 1996, 122 pages http://wwwlib.umi.com/dissertations/fullcit/9625925

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An Economic Evaluation of Percutaneous Transluminal Coronary Angioplasty (PTCA) Versus Coronary Artery Bypass Surgery (CABG) for the Treatment of Multivessel Coronary Artery Disease (Angioplasty, Bypass Surgery, Health Economics) by Mauldin, Patrick Duriez, PhD from Emory University, 1993, 122 pages http://wwwlib.umi.com/dissertations/fullcit/9323175

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

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CHAPTER 5. CLINICAL TRIALS AND ANGIOPLASTY Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning angioplasty.

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

Bypass Angioplasty Revascularization Investigation in Type 2 Diabetics (BARI 2D) Condition(s): Coronary Disease; Cardiovascular Diseases; Heart Diseases; Insulin Resistance; Diabetes Mellitus; Diabetes Mellitus, non-insulin dependent Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The BARI 2D trial is a multicenter study that uses a 2x2 factorial design, with 2800 patients being assigned at random to initial elective revascularization with aggressive medical therapy or aggressive medical therapy alone with equal probability, and simultaneously being assigned at random to an insulin providing or insulin sensitizing strategy of glycemic control (with a target value for HbA1c of <7.0% for all patients). SPECIFIC AIMS A. Primary Aim The primary aim of the BARI 2D trial is to test the following two hypotheses of treatment efficacy in 2800 patients with Type 2 diabetes mellitus and documented stable CAD, in the setting of uniform glycemic control and intensive management of all other risk factors including dyslipidemia, hypertension, smoking, and obesity: 1. Coronary Revascularization Hypothesis: a strategy of initial elective revascularization of choice (surgical or catheter-based) combined with aggressive medical therapy results in lower 5-year mortality compared to a strategy of aggressive medical therapy alone; 2. Method of Glycemic Control Hypothesis: with a target HbA1c level of <7.0%, a strategy of hyperglycemia management directed at insulin sensitization results in lower 5-year mortality compared

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These are listed at www.ClinicalTrials.gov.

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to a strategy of insulin provision. B. Secondary Aims The secondary aims of the BARI 2D trial include: a) comparing the death, myocardial infarction or stroke combined endpoint event rate between the revascularization versus medical therapy groups and between the insulin sensitization versus insulin provision groups; b) comparing rates of myocardial infarction, other ischemic events, angina and quality of life associated with each revascularization and hyperglycemia management strategy; c) evaluating the relative economic costs associated with the trial treatment strategies, d) exploring the effect of glycemic control strategy on the progression and mechanism of vasculopathy including changes in PAI-1 gene expression. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006305 •

Magnetic Resonance Imaging to Investigate Silent Strokes During Neck and Skull Angioplasty Condition(s): Brain Ischemia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will use magnetic resonance imaging (MRI) to determine if silent strokes occur during angioplasty of the blood vessels in the neck or skull. Neck and skull angioplasties are relatively new procedures whose possible complications are still under investigation. Patients 18 years of age or older who are admitted to Suburban Hospital in Bethesda, Maryland, for angioplasty of one or more of the blood vessels in the neck or skull may participate in this study. Participants must be able to undergo a brain MRI. Within 24 hours before their angioplasty, patients will provide a medical history and have a physical examination and brain MRI. The physical examination and MRI will be repeated within 24 hours after the angioplasty. MRI is a diagnostic test that uses a magnetic field and radio waves to show structural and chemical changes in tissues. This technique is more sensitive than X-rays in detecting some changes that occur in diseases of the brain. For the procedure, the patient lies on a table that slides into a metal cylinder (the scanner). The confined space may produce anxiety in some patients, and patients can talk to the technician at all times during the procedure. Earplugs are provided to muffle loud knocking and pulsing noises that occur while the scanner is taking pictures. During the study, the contrast material gadolinium may be injected into an arm vein. Gadolinium "brightens" the pictures, producing better images of brain blood flow. Patients will be contacted by telephone 30 days after the procedure to follow how they are doing and learn whether any complications resulted from the angioplasty. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015717

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MRI to Detect Embolism Following Angiography and Angioplasty-Stenting of the Renal Artery Condition(s): Renal Artery Obstruction; Kidney Disease

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Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will use magnetic resonance imaging (MRI) to picture the kidney and renal arteries (arteries that supply blood to the kidney) in patients scheduled for kidney artery angiogram and angioplasty/stenting procedures. An angiogram is a way of taking pictures of arteries that shows areas of narrowing caused by atherosclerosis-a buildup of plaque on the vessel wall. Angioplasty/stent is a treatment procedure in which a balloon-tipped catheter is inserted in the artery and advanced to the area of blockage to open the vessel, increasing blood flow to the kidney. A permanent metal tube (stent) may or may not be put in place to maintain the opening. During either of these invasive procedures, small pieces of plaque can break off and travel in the blood to lodge elsewhere in the body. This is called embolization. Lodged in the kidney, the embolus can impair kidney function. Currently, these emboli cannot be detected. A new way of visualizing the kidneys that allows detection of emboli may reveal whether material has moved to the kidneys and predict if there will be any kidney damage. Patients 21 years of age and older with suspected kidney artery disease scheduled for invasive angiographic evaluation in NIH protocol 95-H-0047 may be eligible for this study. Participants will be assigned to one of two study groups, based on the angiogram findings and the decision to have the angioplasty/stent procedure. Participants in both groups will have baseline MRI scans up to 2 weeks before the invasive procedure (angiogram with or without angioplasty/stent) and again within a day after the procedure. Patients who undergo angioplasty/stent will have another MRI study within about a month following the procedure. MRI uses a magnetic field and radio waves to produce images of body tissues. The patient lies on a table that slides into a large hollow tube (the scanner). During part of the scan, a material called gadolinium contrast may be injected into a vein. This substance brightens the images to better show the kidneys, their blood vessels and blood flow. The procedure lasts from about 1 to 2 hours. During the MRI, the heart is monitored with an electrocardiogram (EKG) and breathing is monitored with a flexible belt. Blood pressure is measured intermittently. The patient can communicate with a staff member at all times. Blood samples will be drawn from an arm vein at the initial clinic visit, within a day after the procedure and about 1 week after the procedure. For patients who had the angioplasty/stent procedure, a third blood sample will be taken within another 6 six weeks. The blood samples will be used to check for changes in kidney function. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027469 •

Open-label Prostaglandin E1 {Liprostin] treatment with lower limb angioplasty for Peripheral Arterial Occlusive Disease Condition(s): Peripheral Vascular Disease Study Status: This study is currently recruiting patients. Sponsor(s): Endovasc Purpose - Excerpt: This is the first clinical research trial in which intravenous Prostaglandin E1 (PGE1 is a vasoactive hormone) will be used as supportive treatment along with the angioplasty procedure to treat or open up a blocked artery within one lower limb or the most affected of two limbs in subjects with Peripheral Arterial

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Occlusive Disease. PAOD results in a decrease in arterial blood flow to the lower limb and feet with symptoms that can include, pain at rest, a numbing sensation in limb or feet, limited ability to walk before pain occurs. PAOD can occur along with diabetic ulcers. Proposed treatment will be given at a medical center with an overnight hospital stay. Treatment includes angioplasty to open up one or two occluded arteries in a lower limb plus a drug (Liprostin) a special formulation of liposomal Prostaglandin E1,or PGE1, a natural occuring vasoactive hormone). Drug treatment is given twice to each artery to be treated, just before and after angioplasty. When angioplasty procedure is completed, a 12 hour intravenous infusion of Liprostin is given to complete the treatment procedure. A total of 12 PAOD subjects will be enrolled in a single center: Memorial Hermann Hospital, Houston, TX. Study will begin in February, 2003 with the last (12th) subject to be enrolled, likely by August, 20 Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053716 •

Bypass Angioplasty Revascularization Investigation (BARI) Condition(s): Angina Pectoris; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Heart Diseases; Myocardial Ischemia Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To assess the relative long-term safety and efficacy of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) surgery in patients with multivessel disease and severe angina or ischemia who required revascularization and had coronary anatomy suitable for either procedure. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000462

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Percutaneous Transluminal Coronary Angioplasty (PTCA) Registries I, II, and III and the Dynamic Registry Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) and alternative angioplasty devices in patients with coronary heart disease. There are four registries. The first registry followed 3,079 patients who received PTCA between 1977 and 1982. The second registry followed 1,500 patients from the first registry for a minimum of five years and followed 2,000 newly entered patients who received PTCA in 1985 and 1986 so that the second cohort would also be followed for five years. The third registry, the New Approaches to Coronary Intervention (NACI), followed approximately 4,424 patients between November 1990

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and February 1997. The dynamic evaluation study will follow a total of 6,000 procedures. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005677 •

A blinded study conducted at multiple centers evaluating various doses of an investigational agent (BO-653) against placebo, for safety and effectiveness in preventing post-angioplasty blood vessel re-closure (restenosis) in stented vessels. Condition(s): Graft Occlusion, Vascular; Coronary Restenosis; Atherosclerosis Study Status: This study is completed. Sponsor(s): Chugai Pharma USA Purpose - Excerpt: This research study is intended to evaluate the safety and effectiveness of 3 different doses of BO-653, an investigational inhibitor of LDL cholesterol oxidation, when given orally twice a day compared to placebo (an inactive substance) in preventing restenosis (closure of vessel) within six months after stent implantation. Patients must be enrolled into this study within 24 hours after the stenting procedure. Additionally, over a 1- to 9-month post-stent period, the study will compare the safety and effectiveness of BO-653 versus placebo for measures of coronary artery vessel size by quantitative coronary angiography, major adverse cardiac events, and effects on the oxidative status of plasma lipids and other plasma components. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055510

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Biobehavioral Predictors of Coronary Angioplasty Outcome Condition(s): Cardiovascular Diseases; Heart Diseases; Coronary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine some of the psychosocial predictors of poor outcome among revascularized coronary artery disease patients. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005554

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Do Fish Oils Prevent Restenosis Post-Coronary Angioplasty? Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)

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Purpose - Excerpt: To determine whether a dietary supplement of n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil would decrease the restenosis rate in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000473 •

Emory Angioplasty Versus Surgery Trial (EAST) Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare the efficacy of coronary artery bypass graft (CABG) surgery with percutaneous transluminal coronary angioplasty (PTCA) in patients with multiple vessel coronary heart disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000465

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Magnetic Resonance Imaging to Detect Blood Vessel Inflammation in Patients Undergoing Peripheral Balloon Angioplasty Condition(s): Atherosclerosis; Peripheral Vascular Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine the use of magnetic resonance imaging (MRI) in detecting blood vessel inflammation. The results of this study may later be applied to diagnosing inflammation of arteries in patients with atherosclerosis, predicting disease progression in these patients, and guiding therapy. Patients with peripheral artery disease (for example, blockage of a leg artery) undergoing balloon angioplasty at Suburban Hospital in Bethesda, Maryland, may be eligible to participate in this study. Because this procedure, which opens blocked arteries, can cause inflammation in the vessel wall, it affords an opportunity for studying MRI detection of such inflammation. Study candidates will be screened with a medical history and physical examination. Participants will have a MRI scan and blood drawn at Suburban Hospital before the angioplasty and again either 1 to 3 days or 2 weeks after the procedure. Before the MRI scan is begun, a catheter (a thin plastic tube) is inserted in an arm vein and 90 milliliters (about 3 ounces) of blood is drawn. The patient then lies on a table that slides into the MRI scanner-a large donut-shaped machine with a magnetic field. A flexible, padded sensor called an MRI coil is placed over the area to be imaged; this device is used to improve the quality of the pictures. During the scan a contrast material called gadolinium is injected through the catheter. Gadolinium brightens the image of the blood vessels. The procedure lasts up to 2 hours. Phase(s): Phase I

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004549 •

Platelet-Inhibitor Drug Trial in Coronary Angioplasty Condition(s): Angina Pectoris; Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effectiveness of dipridamole and aspirin in prevention of restenosis of the dilated lesion in patients who had undergone percutaneous transluminal coronary angioplasty (PTCA). Secondary aims were to determine the effectiveness of platelet inhibitor therapy in reducing the incidence of coronary events and the severity and incidence of angina. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000510

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Potential Role of CMV in Restenosis Following Angioplasty, in Atherosclerosis, and in Endothelial Dysfunction Condition(s): Arterial Occlusive Cytomegalovirus Infections

Diseases;

Atherosclerosis;

Coronary

Disease;

Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The purpose of this study is to investigate whether the susceptibility of subjects to atherosclerosis is influenced by prior CMV exposure, whether the susceptability to endothelial dysfunction in patients with and in patients without atherosclerosis is influenced by prior CMV exposure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001531

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 “angioplasty” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 6. PATENTS ON ANGIOPLASTY 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 “angioplasty” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on angioplasty, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Angioplasty By performing a patent search focusing on angioplasty, 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 angioplasty: •

1, 3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders Inventor(s): Hoong; Lee K. (Suwanee, GA), Meng; Charles Q. (Alpharetta, GA), Ni; Liming (Duluth, GA), Sikorski; James A. (Alpharetta, GA) Assignee(s): Atherogenics, Inc. (alpharetta, Ga) Patent Number: 6,608,101 Date filed: June 20, 2001 Abstract: It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, postangioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Excerpt(s): The present invention includes novel heteroaryl or heterocyclic 1,3-bis(substituted-phenyl)-2-propen-1-ones as well as methods and compositions for the treatment of disorders mediated by VCAM-1 or MCP-1 and for the treatment of inflammatory disorders generally that include the administration of a 1,3-bis(substituted-phenyl)-2-propen-1-one that has at least one phenyl substituent that is an aryl, heteroaryl or heterocyclic moiety. Adhesion of leukocytes to the endothelium represents a fundamental, early event in a wide variety of inflammatory conditions, autoimmune disorders and bacterial and viral infections. Leukocyte recruitment to endothelium is mediated in part by the inducible expression of adhesion molecules on the surface of endothelial cells that interact with counterreceptors on immune cells. Endothelial cells determine which types of leukocytes are recruited by selectively expressing specific adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. VCAM-1 binds to the integrin VLA-4 expressed on lymphocytes, monocytes, macrophages, eosinophils, and basophils but not neutrophils. This interaction facilitates the firm adhesion of these leukocytes to the endothelium. VCAM-1 is an inducible gene that is not expressed, or expressed at very low levels, in normal tissues. VCAM-1 is upregulated in a number of inflammatory diseases, including arthritis, asthma, dermatitis, psoriasis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Coronary heart disease (CHD), primarily as a result of atherosclerosis, remains the leading cause of death in industrialized countries. Atherosclerosis is a disease characterized by vascular inflammation, deposition of lipids in the arterial vessel wall and smooth muscle cell proliferation resulting in a narrowing of the vessel passages. In advanced stages of the disease atherosclerotic lesions can become unstable resulting in plaque rupture, thrombosis, myocardial infarction and

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ischemic heart disease. It is now well accepted that the initiating events in atherosclerosis are local injury to the arterial endothelium that results in the induction of VCAM-1 and recruitment of mononuclear leukocytes that express the integrin counterreceptor, VLA-4, (O'Brien, et al., J. Clin. Invest., 92: 945-951, 1993). Subsequent conversion of leukocytes to foamy macrophages results in the synthesis of a wide variety of inflammatory cytokines, growth factors, and chemoattractants that help propagate formation of the mature atheromatous plaque by further inducing endothelial activation, leukocyte recruitment, smooth muscle cell proliferation, and extracellular matrix deposition. Pharmacological inhibition of VCAM-1 expression has been shown to inhibit atherosclerosis in several animal models (Sundell et al., Circulation, 100: 42, 1999). A monoclonal antibody against VCAM-1 has also been shown to inhibit neointimal formation in a mouse model of arterial wall injury (Oguchi, S., et al., Arterioscler. Thromb. Vasc. Biol., 20: 1729-1736, 2000). Web site: http://www.delphion.com/details?pn=US06608101__ •

Angioplasty apparatus facilitating rapid exchanges Inventor(s): Yock; Paul G. (Menlo Park, CA) Assignee(s): Scimed Life Systems, Inc. (maple Grove, Mn) Patent Number: 6,585,657 Date filed: July 16, 2001 Abstract: The invention provides a nested tubing cannula which comprises outer and inner elongate tubular members, both having a proximal end, a distal end, and a lumen therebetween. The inner tubular member is sealed at its distal end and is nested substantially coaxially within the lumen of the outer tubular member, so that the gap between the inner and the outer tubular member defines a second lumen whereas the first lumen is the lumen of the inner tubular member. A tubular sleeve is disposed coaxially between the inner and outer tubular members. A balloon is mounted on a distal region of the outer tubular member and is in communication with the first lumen. The cannula further comprises a port proximal or distal the balloon occluder and is in communication with the second lumen. Methods for making the devices herein are disclosed. Excerpt(s): This invention relates to angioplasty apparatus facilitating rapid exchanges and a method for making rapid exchanges of angioplasty devices. At the present time in practicing angioplasty, it is often necessary to exchange one dilatation catheter for another. In doing so, it has been necessary to utilize long exchange wires having a length of approximately 300 centimeters which typically requires two operators to perform the procedure. During this procedure, it is necessary that the operators communicate with each other which makes the procedure time consuming. In addition, since the exchange wire is so long it often is awkward to handle and for that reason may come in contact with the floor or become contaminated which necessitates removing the entire apparatus being utilized for the angioplasty procedure. There is therefore a need for a new and improved angioplasty apparatus which overcomes such difficulties. In general, it is an object of the present invention to provide an angioplasty apparatus and a method which facilitates rapid exchanges of various types of devices. Web site: http://www.delphion.com/details?pn=US06585657__

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Angioplasty stents Inventor(s): Gaschino; Paolo (Chivasso, IT), Rolando; Giovanni (Chivaso, IT) Assignee(s): Sorin Biomedica Cardio S.p.a. (saluggia (vc) Patent Number: 6,616,690 Date filed: October 30, 2001 Abstract: An angioplasty stent comprises a body comprising a plurality of successive segments connected in pairs by bridge means so that the successive segments can be oriented relative to one another for the purposes of bending of the body in any direction defined by a linear combination of respective orientation axes defined by the bridge connection means. During the radial expansion of the stent, the axial contraction of the segments resulting from the opening-out of the respective loops is compensated by axial projection of the bridge elements from the respective concave portions. The wall of the body comprises arms for supporting a lumen as well as regions which are selectively deformable during the expansion of the stent, the arms and the selectively deformable regions having different cross-sections and/or cross-sectional areas. At least one portion of the body may have a substantially reticular structure, the branches of which define geometrical figures identifiable as fractals. Excerpt(s): The present invention relates in general to so-called stents for angioplasty. The term "stent" is intended to indicate in general a device to be fitted in a lumen (for example, inside a blood vessel), usually by catheterization, and subsequently spread out in situ in order to support the lumen locally. This has the main purpose of preventing the re-establishment of a stenotic site in the location treated. It should, however, be pointed out that it has already been proposed in the art to use substantially similar structures for spreading-out and anchoring vascular grafts in situ; naturally this possible extension of the field of application is also intended to be included in the scope of the invention. For a general teaching with regard to vascular stents, reference may usefully be made to the work "Textbook of Interventional Cardiology" by Eric J. Topol, W. B. Saunders Company, 1994 and, in particular, to Section IV of Vol. II, entitled "Coronary stenting". Web site: http://www.delphion.com/details?pn=US06616690__

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Apparatus and method for placing bifurcated stents Inventor(s): Besselink; Petrus (Gronausestraat 1220, Enschede 7534, NL) Assignee(s): None Reported Patent Number: 6,669,718 Date filed: July 18, 2001 Abstract: An apparatus and method to place a bifurcated stent into a body lumen by using a delivery device requiring only one incision. Relative axial movements between a catheter and a sheath in the delivery device permit the insertion and expansion of the stent. During placement into and removal from the patient's body, the branch sections of the bifurcated stent are held in substantially parallel arrangement. Opposing tendencies between a self-expanding stent and leg portions within the delivery device can be tailored such that, during deployment, the bifurcation bias due to the elastic spring forces in the stent overcome the parallel bias within the delivery device. In situations where a balloon-expandable stent is used, the delivery device obviates the need for

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balloon change during stent placement. Such catheters can also be used for angioplasty, eventually in combination with stenting, and are also equally applicable to both multibranch and side branch body lumens, which are difficult to reach with conventional devices and techniques. Excerpt(s): The present invention generally relates to a device and method for delivering an expandable endoluminal prosthetic device, such as a stent, and more particularly to a device and method for placing a bifurcated stent such that only a single incision into a patient need be made. Expandable surgical devices, such as stents and angioplasty balloons, are used in a variety of places in the human body to support various anatomical lumens, such as blood vessels, respiratory ducts, gastrointestinal ducts and the like. Conventionally, these devices are deployed in regions of stenosis or constriction in the target body lumen to hold the lumen open, thus obtaining a patent lumen and preventing immediate or future occlusion or collapse of the lumen and the resultant obstruction of fluids flowing therethrough. Because stent and balloon implantation is a relatively non-invasive procedure, it has proven to be a favorable alternative to surgery in, for example, certain cases of vascular stenosis. Bifurcated devices, with their trunk and branching configuration, are particularly well-suited for use in branching body lumen systems, such as in the coronary vasculature (which include the right, left common, left anterior descending and circumflex arteries and their branches) and the peripheral vasculature (including branches of the carotid, aorta, femoral, popliteal, and related arteries). Placement of such a bifurcated device can be rather complicated, often involving approaching the bifurcated section of the artery through at least two side branches or through the trunk plus one side branch. This procedure can be not only time-consuming, but also lead to more incision sites in the patient's body, as well as necessitate more complicated maneuvers for the surgeon. Procedures for placement of a bifurcated stent are described in U.S. Pat. No. 5,720,735 to Dorros, entitled "Bifurcated Endovascular Catheter" and U.S. Pat. No. 4,994,071 to MacGregor, entitled "Bifurcating Stent Apparatus and Method". In these patents, which are representative of the state of the art, each of the branches has a dedicated guide wire to guide the placement of balloons, stents, stent grafts or grafts into a bifurcated anatomical lumen. This redundancy can lead to increases in the overall size, cost and complexity of delivery devices. Accordingly, there exists a need for an apparatus used to place bifurcated stents and related surgical devices into a body lumen such that simpler surgical procedures are enabled, with a concomitant decrease in incision number or size and related invasive steps, thereby reducing patient trauma associated with complex medical procedures. Web site: http://www.delphion.com/details?pn=US06669718__ •

Balloon shoulder designs Inventor(s): Gaudoin; Henri A. (Mountain View, CA), Jacobson; David T. (San Jose, CA) Assignee(s): Advanced Cardiovascular Systems, Inc. (santa Clara, Ca) Patent Number: 6,652,485 Date filed: May 31, 2000 Abstract: An inflatable member suitable for angioplasty or other medical procedures comprising asymmetric conic shoulder portions that optimize the wrapped profile. The asymmetry distributes the inflatable member material of the shoulder portions over a larger area to reduce the inflatable member profile and improve flexibility. Optionally, the asymmetrical shoulder portions preformed creases to facilitate folding. In an alternate embodiment, each shoulder portion has at least three radially spaced

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preformed creases to optimize folding in the shoulder portion. The invention also comprises methods of forming such inflatable members, the methods generally comprising using molds having the requisite characteristics. Specifically, the mold may have ridges within the areas corresponding the shoulder portions to form the preformed creases when the inflatable member is blow molded. Excerpt(s): The invention relates to the field of intravascular delivery systems, and more particularly to dilatation balloon catheters. Angioplasty balloons must be able to expand to a relatively large diameter in order to dilate stenosed regions of the vasculature effectively. However, it is also desirable for the angioplasty balloons to exhibit a minimal profile when deflated to facilitate introduction into and travel within the vasculature. A small crossing profile also allows the balloon to be positioned across the lesion. Furthermore, the deflated balloon should be sufficiently flexible to allow the balloon to be advanced through the often tortuous coronary anatomy. To obtain a minimized deflated profile, the prior art has adopted various strategies to cause the balloon to preferentially fold into a compact shape when deflated. Typically, these strategies involve preformed creases that cause the balloon material to fold into flaps that then may be wrapped to minimize profile. Nevertheless, these attempts remain an incomplete solution to the problems of minimizing balloon profile. Web site: http://www.delphion.com/details?pn=US06652485__ •

Catheter and guide wire Inventor(s): Usami; Akino (Tokyo, JP), Usami; Gono (Tokyo, JP), Usami; Kaya (Tokyo, JP), Usami; Keiko (Tokyo, JP), Usami; Masano (Tokyo, JP), Usami; Nano (Tokyo, JP), Usami; Nobuko (Tokyo, JP), Usami; Shino (Tokyo, JP), Usami; Tomono (Tokyo, JP) Assignee(s): Usaminanotechnology Inc. (tokyo, Jp) Patent Number: 6,610,046 Date filed: December 29, 2000 Abstract: A catheter and guide wire in which at least a distal end portion of a catheter body or guide wire is formed of a shape memory-specialized metal having shape memory property, but free from superelasticity or pseudoelasticity at least at the body temperature, have high safety and improved operability as compared with prior art ones and are advantageously used in a wide range of examination and treatment, especially in angiography, angioplasty, embolization, foreign matter removal and recovery, calculus capture and so on. Excerpt(s): This invention relates to a medical catheter and guide wire which have high safety and improved operability and are advantageously used in a wide range of examination and treatment, especially in angiography, angioplasty, embolization, retriever/recovery of foreign body, and calculus capture. Conventional catheters designed to be inserted into blood vessels and ureters for examination and treatment purposes include, for example, those used in angiography, intravascular medicament administration, intravascular surgery, ureterolithotomy, and endoscopic retrograde cholangiopancreatography (ERCP). There have been proposed several catheters of this type including a tube of a flexible polymer having a leading metallic guide wire inserted therein, a tube of polyethylene having stainless steel wire braided in a mesh fashion, and a helically cut stainless steel tube enclosed in a synthetic resin (see JP-A 6-134034 and JPA 7-96037). Web site: http://www.delphion.com/details?pn=US06610046__

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Catheter having exchangeable balloon Inventor(s): Gertner; Kevin (Los Gatos, CA), Sirhan; Motasim (Sunnyvale, CA), Yan; John (Los Gatos, CA) Assignee(s): Avantec Vascular Corporation (sunnyvale, Ca) Patent Number: 6,569,180 Date filed: June 2, 2000 Abstract: An intravascular balloon catheter comprises a tubular catheter body having a balloon structure removably mounted over the catheter body. The catheter body has a guidewire lumen , and the catheter body may be left in place within a patient's vasculature while the balloon structure is withdrawn and optionally a second balloon structure introduced over the catheter body. The catheter and methods of the present invention are particularly suitable for performing angioplasty and subsequent procedures, such as stent placement, which are best performed using successive interventional balloon structures. Excerpt(s): The present invention relates generally to medical devices and methods. More particularly, the present invention relates to a balloon catheter having an exchangeable balloon structure. Percutaneous transluminal angioplasty procedures have become a therapy of choice for treating stenosed regions in the patient's vasculature, particularly the coronary vasculature. Recently, the use of such angioplasty procedures has often been combined with stent placement and/or radiation treatment to inhibit restenosis and hyperplasia following angioplasty. When performing such multiple, sequential treatments, it is usually necessary to "exchange" catheters which are used to perform each of the procedures. That is, the initial angioplasty treatment will be performed using a balloon angioplasty catheter. After the angioplasty is completed, a second catheter carrying a stent or other vascular prosthesis must then be introduced to the treatment site. Introduction of the second catheter involves first removing the balloon angioplasty catheter and then placing the second catheter in the treatment region. Optionally, a third catheter may then be exchanged for the second in order to perform radiation or other treatments in order to inhibit hyperplasia. In performing such multiple, sequential treatments, most physicians prefer to leave a "guidewire" in place to the treatment location. A guidewire is a small diameter, highly flexible wire that can be steered to the target location through the vasculature and which then acts as a guide path for introducing and positioning the balloon angioplasty and other interventional catheters. Web site: http://www.delphion.com/details?pn=US06569180__

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Catheter support for stent delivery Inventor(s): Blaeser; David J. (Champlin, MN), Brown; Terry V. (Fridley, MN), Dusbabek; Andrew J. (Dayton, MN), Ellis; Louis G. (St. Anthony, MN), Euteneuer; Charles L. (St. Michael, MN), Larson; Christoper R. (St. Paul, MN), Mattison; Richard C. (Zimmerman, MN), Mertens; Steven P. (New Hope, MN) Assignee(s): Scimed Life Systems, Inc. (maple Grove, Mn) Patent Number: 6,610,069 Date filed: December 4, 2001

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Abstract: An angioplasty and stent delivery system to facilitate introduction and placement of a stent, including a catheter having an expandable distal portion constructed and arranged for expanding the outer diameter of the catheter from a contracted state to an expanded state: a stent positioned around the distal portion of the catheter having a contracted condition and being expandable to an expanded condition, and being sized in the contracted condition to closely surround the catheter in the contracted state, the expandable distal portion of the catheter including a balloon within which or over which there is included on a catheter shaft at least one axially movable or enlargeable body of a diameter larger than the catheter shaft to which the stent and balloon are fitted, as by crimping, for holding the stent in place until it is released therefrom by expansion of the balloon. Excerpt(s): In typical PTCA procedures, a guiding catheter is percutaneously introduced into the cardiovascular system of a patient through a vessel and advanced through therein until the distal end thereof is at a desired location in the vasculature. A guidewire and a dilatation catheter having a balloon on the distal end thereof are introduced through the guiding catheter with the guidewire sliding through the dilatation catheter. The guidewire is first advanced out of the guiding catheter into the patient's coronary vasculature and the dilatation catheter is advanced over the previously advanced guidewire until the dilatation balloon is properly positioned across the lesion. Once in position across the lesion, the flexible, expandable, preformed balloon is inflated to a predetermined size with a liquid or gas at relatively high pressures, such as greater than about four atmospheres, to radially compress the arthrosclerotic plaque of the lesion against the inside of the artery wall and thereby dilate the lumen of the artery. The balloon is then deflated to a small profile so that the dilatation catheter may be withdrawn from the patients vasculature and blood flow resumed through the dilated artery. In angioplasty procedures of the kind described above, there may be restenosis of the artery, which either necessitates another angioplasty procedure, a surgical by-pass operation, or some method of repairing or strengthening the area. To prevent restenosis and strengthen the area, a physician can implant an intravascular prosthesis, called a stent, for maintaining vascular patency inside the artery at the lesion. The stent is expanded to a larger diameter for placement or implantation in the vasculature, often by the balloon portion of the catheter. Stents delivered to a restricted coronary artery, expanded to a larger diameter as by a balloon catheter, and left in place in the artery at the site of a dilated lesion are shown in U.S. Pat. No. 4,740,207 to Kreamer; U.S. Pat. No. 5,007,926 to Derbyshire; U.S. Pat. No. 4,733,665 to Palmaz; U.S. Pat. No. 5,026,377 to Burton et al.; U.S. Pat. No. 5,158,548 to Lau et al.; U.S. Pat. No. 5,242,399 to Lau et al.; U.S. Pat. No. 5,344,426 to Lau et al.; U.S. Pat. No. 5,415,664 to Pinchuk; U.S. Pat. No. 5,453,090 to Martinez et al.; U.S. Pat. No. 4,950,227 to Savin; U.S. Pat. No. 5,403,341 to Solar; U.S. Pat. No. 5,108,416 to Ryan et al., U.S. Pat. No. 5,242,451 to Harada and European Patent Application No. 707 837 A1 to Sheiban, all of which are incorporated herein by reference. A stent particularly preferred for use with this invention is described in PCT Application No. 960 3092 A1, published Feb. 8, 1996, the content of which is also incorporated herein by reference. The present invention is particularly directed to improved arrangements for catheters of reduced profile for performing angioplasty and for releasably attaching the stent to the catheter to facilitate delivery thereof. The invention is applicable to all the various types of catheters used in such procedures, including rapid exchange types and over-the-wire types. Web site: http://www.delphion.com/details?pn=US06610069__

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Catheter system with catheter and guidewire exchange Inventor(s): Kramer; Barry L. (Chicago, IL) Assignee(s): Advanced Cardiovascular Systems, Inc. (santa Clara, Ca) Patent Number: 6,685,721 Date filed: May 12, 1992 Abstract: An intravascular catheter system, such as a dilatation catheter system for angioplasty procedures, which provides for the replacement of the catheter or the guidewire thereof during the procedure. The intravascular catheter has an guidewirereceiving inner lumen extending along the length thereof. A first guidewire port is provided in the catheter body at or near the proximal end of the catheter, a second guidewire port is provided in the catheter body at a location spaced distally from the first guidewire port and proximally from a diagnostic or therapeutic element, such as a dilatation balloon, on a distal portion of the catheter and a third guidewire port is provided in the distal end of the catheter. The guidewire ports are in communication with the guidewire-receiving inner lumen. Excerpt(s): This invention generally relates to a catheter system which is suitable for intravascular procedures such as percutaneous transluminal coronary angioplasty (PTCA) and which allows for the exchange of guidewires and catheters during such procedures. In classic PICA procedures, a guiding catheter having a preshaped distal tip is percutaneously introduced into the cardiovascular system of a patient and advanced therein until the preshaped distal tip thereof is disposed within the aorta adjacent the ostium of the desired coronary artery. The guiding catheter is twisted or torqued from the proximal end to turn the distal tip of the guiding catheter so that it can be guided into the coronary ostium. A dilatation catheter having a balloon on the distal end thereof and a guidewire slidably disposed within an inner lumen of the dilatation catheter are introduced into and advanced through the guiding catheter to the distal tip thereof. The distal tip of the guidewire is usually manually shaped (i.e. curved) by the physician or one of the attendants before the guidewire is introduced into the guiding catheter along with the dilatation catheter. The guidewire is first advanced out the distal tip of the guiding catheter, which is seated in the ostium of the patient's coronary artery, into the patient's coronary artery. A torque is applied to the proximal end of the guidewire, which extends out of the patient, to guide the curved or otherwise shaped distal end of the guidewire as the guidewire is advanced within the coronary anatomy until the shaped distal end of the guidewire enters the desired artery. The advancement of the guidewire within the selected artery continues until it crosses the lesion to be dilated. The dilatation catheter is then advanced out of the distal tip of the guiding catheter, over the previously advanced guidewire, until the balloon on the distal extremity of the dilatation catheter is properly positioned across the lesion. Once properly positioned, the flexible, relatively inelastic balloon is inflated to a predetermined size with radiopaque liquid at relatively high pressures (e.g., 4-12 atmospheres) to dilate the stenosed region of the diseased artery. The balloon is then deflated so that the dilatation catheter can be removed from the dilated stenosis and blood flow can then be resumed therethrough. Further details of guiding catheters, dilatation catheters, guidewires, and the like for angioplasty procedures can be found in U.S. Pat. No. 4,323,071 (SimpsonRobert); U.S. Pat. No. 4,439,185 (Lundquist); U.S. Pat. No. 4,468,224 (Enzmann et al.); U.S. Pat. No. 4,516,972 (Samson); U.S. Pat. No. 4,438,622 (Samson et al.); U.S. Pat. No. 4,554,929 (Samson et al.); U.S. Pat. No. 4,582,185 (Samson); U.S. Pat. No. 4,616,652 (Simpson); U.S. Pat. No. 4,638,805 (Powell); U.S. Pat. No. 4,748,986 (Morrison et al.); U.S.

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Pat. No. 4,898,577 (Badger et al.); and U.S. Pat. No. 4,748,982 (Horzewski et al.) which are hereby incorporated herein in their entirety by reference thereto. Web site: http://www.delphion.com/details?pn=US06685721__ •

Catheter with improved transition Inventor(s): Garcia; Renee E. (Cupertino, CA), Happ; Dorrie M. (San Jose, CA), Liang; Jessica (Redwood City, CA), Lumauig; Rommel C. (San Jose, CA), Wang; Chicheng Jack (Sunnyvale, CA) Assignee(s): Advanced Cardiovascular Systems, Inc. (santa Clara, Ca) Patent Number: 6,575,958 Date filed: May 23, 2000 Abstract: The invention is generally directed to an intraluminal catheter system with an improved transition between a proximal shaft portion and a more flexible distal shaft portion. The improvement provides enhanced flexibility and kink-resistance, thus, facilitating advancement through tortuous anatomy. The present catheters may be used for either or both angioplasty and stent deployment. Excerpt(s): The invention relates to the field of intravascular catheters, and particularly to a catheter suitable for angioplasty and/or stent deployment, and the like. In percutaneous transluminal coronary angioplasty (PTCA) procedures a guiding catheter is advanced in the patient's vasculature until the distal tip of the guiding catheter is seated in the ostium of a desired coronary artery. A guidewire is first advanced out of the distal end of the guiding catheter into the patient's coronary artery until the distal end of the guidewire crosses a lesion to be dilated. A dilatation catheter, having an inflatable balloon on the distal portion thereof, is advanced into the patient's coronary anatomy over the previously introduced guidewire until the balloon of the dilatation catheter is properly positioned across the lesion. Once properly positioned, the dilatation balloon is inflated with inflation fluid one or more times to a predetermined size at relatively high pressures so that the stenosis is compressed against the arterial wall and the wall expanded to open up the vascular passageway. Generally, the inflated diameter of the balloon is approximately the same diameter as the native diameter of the body lumen being dilated so as to complete the dilatation but not overexpand the artery wall. After the balloon is finally deflated, blood flow resumes through the dilated artery and the dilatation catheter and the guidewire can be removed therefrom. In such angioplasty procedures, there may be restenosis of the artery, i.e. reformation of the arterial blockage, which necessitates either another angioplasty procedure, or some other method of repairing or strengthening the dilated area. To reduce the restenosis rate of angioplasty alone and to strengthen the dilated area, physicians now normally implant an intravascular prosthesis, generally called a stent, inside the artery at the site of the lesion. Stents may also be used to repair vessels having an intimal flap or dissection or to generally strengthen a weakened section of a vessel or to maintain its patency. Stents are usually delivered to a desired location within a coronary artery in a contracted condition on a balloon of a catheter which is similar in many respects to a balloon angioplasty catheter, and expanded within the patient's artery to a larger diameter by expansion of the balloon. The balloon is deflated to remove the catheter and the stent left in place within the artery at the site of the dilated lesion. See for example, U.S. Pat. No. 5,507,768 (Lau et al.) and U.S. Pat. No. 5,458,615 (Klemm et al.), which are incorporated herein by reference. Thus, stents are used to keep open a stenosed vessel, and strengthen the dilated area by remaining inside the vessel. Instead of first using one

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catheter to dilate the body lumen and a second catheter to deploy the stent after the dilatation, the stent may be mounted on a balloon catheter and deployed at the same time the balloon is inflated to dilate the stenotic region. Web site: http://www.delphion.com/details?pn=US06575958__ •

Collapsible blood filter with optimal braid geometry Inventor(s): Adams; Bruce (Malden, MA), Brightbill; Jerry R. (Newton, MA), Brin; David S. (Danvers, MA), Brooks; Dennis L. (Windsor, CA), Douk; Nareak (Lowell, MA), Lashinski; Robert D. (Sebastopol, CA), Malek; Ahmed (Cairo, EG), Rafiee; Nasser (Andover, MA) Assignee(s): Medtronic Ave, Inc. (santa Rosa, Ca) Patent Number: 6,602,271 Date filed: December 12, 2000 Abstract: The present invention is a collapsible blood filter for use during a vascular procedure, such as angioplasty or stent deployment. A filter made of braided filaments is located on the distal end of a delivery member, and the filter is deployed downstream of the vascular treatment site to capture emboli released during and immediately after the procedure. Optimal braid geometry of the filter ensures that captured emboli will be retained during collapse and removal of the filter following the procedure. Excerpt(s): The present invention relates generally to endovascular devices for capturing particulate. More particularly, the invention relates to a filter assembly located at the distal end of a delivery member to capture emboli in a blood vessel during a vascular procedure and then remove the captured emboli from the patient after completion of the procedure. A variety of treatments exists for dilating or removing athersclerotic plaque in blood vessels. The use of an angioplasty balloon catheter is common in the art as a minimally invasive treatment to enlarge a stenotic or diseased blood vessel. This treatment is known as percutaneous transluminal angioplasty, or PTA. To provide radial support to the treated vessel in order to prolong the positive effects of PTA, a stent may be implanted in conjunction with the procedure. Thrombectomy is a minimally invasive technique for removal of an entire thrombosis or a sufficient portion of the thrombosis to enlarge the stenotic or diseased blood vessel may be accomplished instead of a PTA procedure. Atherectomy is another well known minimally invasive procedure that mechanically cuts or abrades a stenosis within the diseased portion of the vessel. Alternatively, ablation therapies use laser or RF signals to superheat or vaporize the thrombis within the vessel. Emboli loosened during such procedures may be removed from the patient through the catheter. Web site: http://www.delphion.com/details?pn=US06602271__

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Corewire securement system Inventor(s): Lenz; Jason T. (Maplewood, MN), Simer, Jr.; Loren J. (Minnetonka, MN), Slayhi; Mirna A. (Minneapolis, MN) Assignee(s): Scimed Life Systems, Inc. (maple Grove, Mn) Patent Number: 6,620,149 Date filed: October 5, 2000

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Abstract: A catheter for use in vasculature or other lumen within body structures includes a shaft formed from an elongated polymeric flexible tube. A metallic tube may be bound to the distal end of this tube. A thinner, more flexible tube may be attached to the distal end of a metallic tube. The two plastic tubes, together with any metallic tube define a lumen for providing communication with an angioplasty balloon or with a body lumen at the distal end of the catheter. A catheter may include a core member to facilitate moving the catheter through a lumen, and to reduce the likelihood that the catheter will kink or bend improperly. This metallic core member extends from the hub to some point distal on the catheter, and may extend to the distal tip of the catheter. The distal end of a catheter balloon may be secured to the core member during manufacture of the catheter. The core member has a zigzagged or helix shape at the proximal end which is friction fit into the hub lumen, and may have a pointed tip that embeds in the hub inner wall. During manufacture, the core member can be secured within the hub with reduced reliance on adhesives or molding of the core member within the hub body. The core member may be secured within the hub by being press fit into the hub lumen. The catheter is more easily manufactured, and has an increased volume and reduced obstruction by adhesive in comparison with other methods of securing the core member. Excerpt(s): The present invention relates to the field of catheterization of lumen within the human body, particularly vasculature. Even more particularly, the invention will have application to the manufacture and construction of balloon catheters used in angioplasty. Angioplasty procedures have gained wide acceptance as an efficient and effective method for treating certain types of vascular diseases. In particular, angioplasty is widely used for stenoses in the coronary arteries, although it is also used for the treatment of stenoses in other parts of the vascular system. The use of core members to provide rigidity and pushability for catheters is well known, and the incorporation of such core members is discussed, for example, in U.S. Pat. No. 5,921,958, entitled Intravascular Catheter with Distal Tip Guide Wire Lumen, which is hereby incorporated by reference. The most widely used form of angioplasty makes use of a dilatation balloon catheter to treat a stenosis and thereby reestablish an acceptable blood flow through the artery. The dilatation catheter includes an elongated tubular shaft and an inflatable balloon carried at a distal end of the shaft. In operation, the catheter is inserted through a guide catheter which has been previously introduced into a patient's vascular system from a location remote from the heart (e.g., femoral artery). The proximal end of the guide catheter remains outside the patient while the distal end of the guide catheter is positioned at the coronary artery ostium. A dilatation catheter is introduced into the proximal end of the guiding catheter and advanced to the distal end of the guide catheter. Then, by using fluoroscopy, the physician guides the dilatation catheter the remaining distance through the vascular system until the balloon is positioned across the stenosis. Web site: http://www.delphion.com/details?pn=US06620149__ •

Cryoplasty device and method Inventor(s): Lafontaine; Daniel M. (Plymouth, MN) Assignee(s): Scimed Life Systems, Inc. (maple Grove, Mn) Patent Number: 6,648,878 Date filed: July 25, 2001 Abstract: A cryoplasty catheter and method for preventing or slowing reclosure of a lesion following angioplasty. The cryoplasty catheter includes a shaft having proximal

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and distal ends and a dilatation balloon disposed at the distal end. An intake lumen and exhaust lumen are defined by the shaft to deliver coolant to the balloon and to exhaust or drain coolant from the balloon. The method in accordance with the present invention includes cooling a lesion to aid in remodeling the lesion through dilatation and/or freezing a portion of the lesion adjacent the dilatation balloon to kill cells within the lesion to prevent or retard restenosis. Excerpt(s): The present invention pertains generally to the field of angioplasty and, in particular, to a form of angioplasty involving lesion cooling. Conventional angioplasty has been preformed for several decades, prolonging the lives of an ever increasing number of patients. Angioplasty procedures involves the dilatation of a balloon placed across a lesion in a coronary artery. Dilatation of the balloon in turn dilates the lesion, opening the artery for increased blood flow. In some cases, however, the goal of the angioplasty procedure is, in whole or in part, frustrated by complete or partial reclosure of the artery at the lesion. Two mechanisms are believed to be principally responsible for reclosure of the artery, these are restenosis and recoil. Restenosis is believed to be caused by continued growth or regrowth of the smooth muscle cells associated with the lesion. Recoil is in part a mechanical process involving elastic rebound of the dilated lesion. Several means have been disclosed for addressing the problem of restenosis. These include, among others, radiation treatments to slow or prevent smooth muscle cell proliferation associated with the restenotic process. Certain drug therapies have been proposed to prevent or slow restenosis. Web site: http://www.delphion.com/details?pn=US06648878__ •

Gels and multilayer surface structures from boronic acid containing polymers Inventor(s): Elbert; Donald L. (Lexington, KY), Hubbell; Jeffrey A. (Zumikon, CH), Winblade; Natalie D. (Seattle, WA) Assignee(s): Eidgenossische Technische Hochschule Zurich (zurich, Ch), Universitat Zurich (zurich, Ch) Patent Number: 6,652,902 Date filed: December 28, 2001 Abstract: Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form crosslinked hydrogels, which are highly swollen in water. The crosslinking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically crosslinked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ, decreasing the incidence or severity of such pathologic conditions as the formation of post-surgical adhesions, and thrombosis following angioplasty. Excerpt(s): This is generally in the field of polymeric materials for modulation of cell to cell interactions, especially for biomedical applications. Biodegradable hydrogels can be carriers for biologically active materials such as hormones, enzymes, antibiotics,

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antineoplastic agents, and cell suspensions. Temporary preservation of functional properties of a carried species, as well as controlled release of the species into local tissues or systemic circulation, are possible. Proper choice of hydrogel macromers can produce membranes with a range of permeability, pore sizes and degradation rates suitable for a variety of applications in surgery, medical diagnosis and treatment. Polymeric hydrogels have also been used as tissue adhesives and sealants. Fibrin gels have been used extensively in Europe as sealants and adhesives in surgery (Thompson et al., 1988, Drug Intell. and Clin. Pharm., 22:946; Gibble et al., 1990, (1990), Transfusion, 30(8): 741). Synthetic polymers have been explored as adhesives (Lipatova, 1986, Advances in Polymer Science 79: 65-93), but these materials have generally been associated with local inflammation, cytotoxicity, and poor biocompatability. Web site: http://www.delphion.com/details?pn=US06652902__ •

Guided filter with support wire and methods of use Inventor(s): Tsugita; Ross S. (Mountain View, CA) Assignee(s): Scimed Life Systems Inc. (maple Grove, Mn) Patent Number: 6,652,505 Date filed: September 29, 2000 Abstract: A guided filter system for temporary placement of a filter in an artery or vein is disclosed. The system includes a guidewire slideable through a wire guide included in a distal region of a support wire. The support wire has an expandable filter, which is operable between a collapsed or enlarged condition. A variety of endovascular devices, including angioplasty, atherectomy, and stent-deployment catheters, are insertable over the guidewire and/or the support wire. Methods of using the guided filter system to direct and exchange endovascular devices to a region of interest, and to entrap and remove embolic material from the vessel are also disclosed. Excerpt(s): The present invention relates generally to devices and methods for providing temporary placement of a filter in a blood vessel. More particularly, the invention provides a guidewire system for entrapment of embolic material in an artery or vein during an endovascular procedure. The system also provides a support wire for directing and/or exchanging other "over the wire" devices, such as angioplasty, atherectomy, or stent deployment catheters, to a region of interest within the vessel. Treatment of thrombotic or atherosclerotic lesions in blood vessels using an endovascular approach has recently proven to be an effective and reliable alternative to surgical intervention in selected patients. For example, directional atherectomy and percutaneous translumenal coronary angioplasty (PTCA) with or without stent deployment are useful in treating patients with coronary occlusion. Atherectomy physically removes plaque by cutting, pulverizing, or shaving in atherosclerotic arteries using a catheter-deliverable endarterectomy device. Angioplasty enlarges the lumenal diameter of a stenotic vessel by exerting mechanical force on the vascular walls. In addition to using angioplasty, stenting, and/or atherectomy on the coronary vasculature, these endovascular techniques have also proven useful in treating other vascular lesions in, for example, carotid artery stenosis, peripheral arterial occlusive disease (especially the aorta, the iliac artery, and the femoral artery), renal artery stenosis caused by atherosclerosis or fibromuscular disease, superior vena cava syndrome, and occlusive iliac vein thrombosis resistant to thrombolysis. It is well recognized that one of the complications associated with endovascular techniques is the dislodgment of embolic materials generated during manipulation of the vessel, thereby

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causing occlusion of the narrower vessels downstream and ischemia or infarct of the organ which the vessel supplies. In 1995, Waksman et al. disclosed that distal embolization is common after directional atherectomy in coronary arteries and saphenous vein grafts. See Waksman et al., American Heart Journal 129(3): 430-5 (1995), incorporated herein by reference. This study found that distal embolization occurs in 28% (31 out of 111) of the patients undergoing atherectomy. In January 1999, Jordan, Jr. et al. disclosed that treatment of carotid stenosis using percutaneous angioplasty with stenting is associated with more than eight times the rate of nicroemboli seen using carotid endarterectomy. See Jordan, Jr, et al. Cardiovascular surgery 7(1): 33-8 (1999), incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06652505__ •

Instrument for thromboembolic protection Inventor(s): Wholey; Mark H. (816 Woodland Ave., Oakmont, PA 15139), Wholey; Michael (19407 Straus, San Antonio, TX 78256) Assignee(s): None Reported Patent Number: 6,652,554 Date filed: January 3, 2000 Abstract: A thromboembolic capturing system captures thromboemboli in the arterial and venous circulation. A vascular tube such as a guidewire includes a porous filter at is distal end. The filter is collapsible, capable of maintaining open and closed configurations when placed within a vessel. Opening and closing of the filter is controlled by strings or sutures running through the tube. The filter is able to retain captured thromboembolic material in conjunction with angioplasty or interventional cardiovascular procedure. When the tube comprises a guidewire, it is of sufficient strength, torquability and softness to be used for angioplasty, stent placement and other interventional procedures. Excerpt(s): The present invention relates to thromboembolic protection, and more particularly relates to an instrument including a collapsible filter mounted on a tube such as a guidewire for thromboembolic protection. It is common practice today to open occluded (i.e., blocked) or stenotic (i.e., narrowed) blood vessels by inserting a guidewire and then a catheter carrying a balloon shaped distal end, and inflating the balloon, which exerts radial force, to press the stenosis outward against the wall of the vessel. This procedure is called balloon angioplasty. Frequently, an implantable metallic stent will be used additionally to provide greater radial strength and longer-term patency. The stent can be delivered with a balloon catheter or on a special sheath. This procedure is called A stent placement. During balloon angioplasty and stent placement of the stenotic lesion, there is the risk of dislodging fragments of plaque, thrombus (blood clots) or other material. If the lesion involves arterial circulation, then the particles could flow into smaller vessels in the brain, other organs or extremities resulting in disastrous complications. Likewise, if the lesions involve the venous circulation, then the thromboemboli could flow into the heart and lung possibly resulting in the demise of the patient. Web site: http://www.delphion.com/details?pn=US06652554__

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Intraluminal therapy catheter with inflatable helical member and methods of use Inventor(s): Stiger; Mark L. (Santa Rosa, CA) Assignee(s): Medtronic Ave, Inc. (santa Rosa, Ca) Patent Number: 6,679,860 Date filed: June 19, 2001 Abstract: The invention is an intraluminal therapy catheter having a least two treatment members disposed near the distal end of the catheter, the members being independently inflatable to perform angioplasty and/or fluid-sourced brachytherapy. A first treatment member is helically mounted about the shaft of the catheter, and forms a helical perfusion channel when inflated into contact with the vessel being treated. In a first embodiment of the invention, the second treatment member is also helically mounted about the catheter shaft and capable of forming a helical perfusion channel when inflated into contact with the vessel. The first and second treatment members are intertwined to form a double helix configuration wherein each member is capable of being inflated to generally fill the helical perfusion channel created by simultaneous inflation of the other member. In a second embodiment of the invention, the second treatment member is a tubular balloon mounted generally coaxially about the catheter shaft, adjacent to the first treatment member. Excerpt(s): The present invention relates to intraluminal therapy devices and more particularly to catheters intended for use in angioplasty and brachytherapy. Stenosis is a narrowing or constriction of a duct or canal. A variety of disease processes, such as atherosclerotic lesions, immunological reactions, congential abnormalities and the like, can lead to stenoses of arteries or other vessels. Stenosis of a coronary artery can reduce blood flow sufficiently to cause myocardial ischemia. Percutaneous transluminal coronary angioplasty (PTCA), the insertion and inflation of a balloon catheter in a coronary artery to affect its repair, is widely accepted as an option in the treatment of obstructive coronary artery disease. In general, PTCA is used to increase the lumen diameter of a coronary artery that is partially or totally obstructed by a build-up of cholesterol fats or atherosclerotic plaque. In PTCA, a coronary guiding catheter provides a channel from outside the patient to the ostium of a coronary artery. A balloon catheter is advanced over a small diameter, steerable guidewire through the guiding catheter, into the artery, and across the stenosis. The tubular balloon near the tip of the catheter is inflated to expand the narrowing. Dilation of the occlusion, however, can form flaps, fissures and dissections which threaten abrupt reclosure of the dilated vessel or even perforations in the vessel wall. To treat or prevent such sequelae, tubular stents are often placed within the angioplasty site to scaffold the vessel lumen. Since a tubular balloon typically occludes, or shuts off blood flow through an artery, angioplasty can be conducted for only short periods before the lack of blood flow may cause ischaemia or tissue damage. To solve this problem, some PTCA catheters include a bypass, or perfusion channel, so that blood continues to flow through the artery during dilatation. In some devices, the perfusion channel is a hollow shaft extending through the balloon. Blood ingress to and egress from the hollow shaft is provided by open ports in the shaft, located proximal and distal to the balloon. In other PTCA catheters, a helical balloon mounted around the catheter shaft forms a spiral perfusion channel between the wall of the vessel and the inflated balloon. The flow rate of blood passing through the spiral channel depends upon the channel cross sectional area, which is related, in part, to the channel width between adjacent turns of the helical balloon. However, widening the channel width to increase flow also decreases the surface area of the stenosis that is exposed to the dilating force of the helical balloon. Thus, there are design trade-offs that

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attend dilatation balloon catheters having spiral perfusion channels. In other prior art perfusion angioplasty catheters, the catheter shaft is mounted off-center within a coiled balloon such that blood can flow through the center of the coil. Web site: http://www.delphion.com/details?pn=US06679860__ •

Irradiation catheter and method of use Inventor(s): Teirstein; Paul S. (1515 Coast Walk, La Jolla, CA 92037) Assignee(s): None Reported Patent Number: 6,585,715 Date filed: July 28, 2000 Abstract: A catheter for use with a radioactive source within the catheter to irradiate a selected area of a blood vessel in combination with angioplasty procedures, to prevent restenosis of that area of the blood vessel. The catheter has a guidewire channel formed near its distal end to facilitate use of the catheter as a rapid exchange catheter, allowing insertion of the catheter over a guidewire also used in performance of an angioplasty procedure. The catheter also has a radiation lumen with a sealed end to retain the radioactive source within the catheter. The radiation lumen is sufficiently longer than the guidewire channel to extend into a non-sterile field, keeping the radiation source segregated from the blood, allowing the use of a non-sterile radiation source. The catheter can also be provided with a centering balloon or a set of centering wire loops to center the radioactive source radially within the blood vessel. Excerpt(s): The present invention is in the field of devices used to subject portions of a blood vessel to nuclear radiation to prevent restenosis of the irradiated area after performance of an angioplasty procedure. A common problem after performance of a percutaneous transluminal coronary angioplasty is the restenosis of the treated area. In fact, restenosis occurs in 30% to 50% of cases. Restenosis occurs, at least in part, as a result of vascular smooth muscle cell migration, proliferation, and neointima formation at the site of the angioplasty. It has been shown that intracoronary delivery of ionizing radiation causes focal medial fibrosis, which when delivered at the site of the angioplasty, impedes the restenosis process. Adjacent coronary segments and the surrounding myocardium are undamaged by the irradiation treatment. Delivery of the ionizing radiation at the site of the stenosis can be achieved by the introduction of an irradiation source, such as a ribbon, through an infusion catheter. In known systems, the infusion catheter is inserted to the site of the stenosis over a guidewire which may be inserted before, or alternatively, left after, the performance of an angioplasty procedure. After insertion of the infusion catheter, the guidewire is removed from the catheter, and the irradiation ribbon is inserted in its place. The irradiation ribbon typically incorporates a plurality of Iridium-192 seeds or pellets near its distal end. Other sources that might not be line sources of ionizing radiation can be used, as well. This plurality of radioactive sources arranged essentially in a line approximates a line source, although the intensity of the radiation will vary axially to some extent, depending upon the spacing and length of the seeds. The irradiation ribbon is inserted to the point where the radioactive material is placed in the area of the stenosis. The Iridium-192 emits gamma radiation having a range of energies between 296 and 612 thousand electron volts (keV). Web site: http://www.delphion.com/details?pn=US06585715__

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Method and composition for inhibiting cardiovascular cell proliferation Inventor(s): Cooke; John P. (Palo Alto, CA), Fathman; Garrison C. (Portola Valley, CA), Kown; Murray H. (Menlo Park, CA), Robbins; Robert C. (Stanford, CA), Rothbard; Jonathan B. (Woodside, CA), Uemura; Shiro (Nara, JP) Assignee(s): Board of Trustees of the Leland Stanford Junior University (stanford, Ca) Patent Number: 6,605,115 Date filed: June 5, 2000 Abstract: Cardiovascular cell proliferation in a blood vessel subjected to trauma, such as angioplasty, vascular graft, anastomosis, or organ transplant, can be inhibited by contacting the vessel with a polymer consisting of from 6 to about 30 amino acid subunits, where at least 50% of the subunits are arginine, and the polymer contains at least six contiguous arginine subunits. Exemplary polymers for this purpose include arginine homopolymers 7 to 15 subunits in length. Excerpt(s): The present invention relates to methods and compositions for inhibiting cardiovascular cell proliferation. The invention provides methods for improving the longevity and quality of arterial grafts, for enhancing vascular NO production, and for reducing post-graft intimal hyperplasia, stenosis, and restenosis. Best, P. J. et al., Arterioscler. Thromb. Vasc. Biol. 19:14-22 (1999). Boger, R. H. et al., "Asymmetric Dimethylarginine (ADMA): A Novel Risk Factor for Endothelial Dysfunction. Its Role in Hypercholestrolemia", Circulation 98:1842-1847 (1998). Web site: http://www.delphion.com/details?pn=US06605115__

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METHOD AND DEVICE FOR PERFORMING COOLING- OR CRYO-THERAPIES FOR, E.G., ANGIOPLASTY WITH REDUCED RESTENOSIS OR PULMONARY VEIN CELL NECROSIS TO INHIBIT ATRIAL FIBRILLATION EMPLOYING MICROPOROUS BALLOON Inventor(s): Kramer; Hans W. (Temecula, CA) Assignee(s): Innercool Therapies, Inc. (san Diego, Ca) Patent Number: 6,685,732 Date filed: August 17, 2001 Abstract: An enhanced method and device are provided to inhibit or reduce restenosis following angioplasty or stent placement. A porous balloon-tipped catheter is disposed in the area treated or opened through balloon angioplasty immediately following angioplasty. The balloon, which can have a dual balloon structure, may be delivered through a guiding catheter and over a guidewire already in place. A fluid such as a perfluorocarbon flows into the balloon to freeze the tissue adjacent the balloon, this cooling being associated with reduction of restenosis. A similar catheter may be used to reduce atrial fibrillation by inserting and inflating the porous balloon such that an exterior surface of the balloon, as well as a portion of the cold working fluid, from the microporosity contacts at least a partial circumference of the portion of the pulmonary vein adjacent the left atrium. Excerpt(s): Balloon angioplasty, or the technology of reshaping of a blood vessel for the purpose of establishing vessel patency using a balloon tipped catheter, has been known since the late 1970's. The procedure involves the use of a balloon catheter that is guided by means of a guidewire through a guiding catheter to the target lesion or vessel

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blockage. The balloon typically is equipped with one or more marker bands that allow the interventionalist to visualize the position of the balloon in reference to the lesion with the aid of fluoroscopy. Once in place, i.e., centered with the lesion, the balloon is inflated with a biocompatible fluid, and pressurized to the appropriate pressure to allow the vessel to open. Typical procedures are completed with balloon inflation pressures between 8 and 12 atmospheres. A percentage of lesions, typically heavily calcified lesions, require much higher balloon inflation pressures, e.g., upward of 20 atmospheres. At times, the balloon inflation procedure is repeated several times before the lesion or blockage will yield. The placement of stents after angioplasty has become popular as it reduces the rate of restenosis. Restenosis refers to the renarrowing of the vascular lumen following vascular intervention such as a balloon angioplasty procedure or stent insertion. Restenosis is clinically defined as a greater than 50% loss of initial lumen diameter. The mechanism or root causes of restenosis are still not fully understood. The causes are multifactorial, and are partly the result of the injury caused by the balloon angioplasty procedure and stent placement. With the advent of stents, restenosis rates have dropped from over 30% to 10-20%. Recently, the use and effectiveness of low-dose radiation administered intravascularly following angioplasty is being evaluated as a method to alter the DNA or RNA of an affected vessel's cells in the hope of reducing cell proliferation. Web site: http://www.delphion.com/details?pn=US06685732__ •

MRI medical device markers utilizing fluorine-19 Inventor(s): Pacetti; Stephen Dirk (San Jose, CA) Assignee(s): Advanced Cardiovascular Systems, Inc. (santa Clara, Ca) Patent Number: 6,574,497 Date filed: December 22, 2000 Abstract: Medical devices that incorporate compounds containing fluorine-19 materials for use as contrast agents and passive markers in interventional magnetic resonance angiography. The device may be a guidewire, guiding catheter, angioplasty catheter, stent, embolic protection device, endovascular graft, endotracheal tube, Foley catheter, Hickman catheter, Broviac catheter, cerebrospinal fluid shunt, biliary stent, stylet, biopsy needle, electrode, percutaneous or endoluminal transducer or other desired interventional medical device. The fluorine-19 material may be configured from an elastomer, a fluid, a fluorosilicone, or a perfluorocarbon grease or oil. Such materials may be incorporated into marker bands and/or stripes, or may be deposited into or dispersed within the walls or lumens of the medical device to be visualized. Use of fluorine-19 containing markers and contrast agents provide a novel method of performing angioplasty and deploying stents, grafts, embolic protection and other such devices using interventional magnetic resonance angiography. Excerpt(s): The present invention relates to apparatus and methods for medical imaging, specifically to the use of passive markers for magnetic resonance imaging. In a particular, the invention relates to the use of fluorine-19 (.sup.19 F) nuclei containing compounds as contrast agents and markers for medical devices used in interventional magnetic resonance angiography. Currently, x-ray fluoroscopy is the preferred imaging modality for cardiovascular interventional procedures. No other method, at this time, has the temporal or spatial resolution of fluoroscopy. As good as fluoroscopy is, however, it does have drawbacks. Catheterization is required in order to directly inject the high concentration of iodinated contrast agent required. Systemic administration of

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the contrast agent would require too high a dose of agent. Additionally, iodinated contrast agents are nephrotoxic with a real incidence of acute renal failure, particularly in patients with compromised renal function. Allergic reactivity also serves as a contraindication for certain patients. Visualization and tracking of devices under fluoroscopy is accomplished either by the device's inherent adsorption of x-rays, or by the placement of radiopaque markers. Fluoroscopy generates a compressed, two dimensional image of what are three dimensional structures. This requires multiple views to appraise complex vasculature. Moreover, fluoroscopy uses ionizing x-ray radiation with its attendant hazards. This is an issue for the patient during protracted or repeated interventions. It is a daily issue for the interventionalist who must also cope with the burden of personal dose monitoring and wearing lead shielding. One imaging modality, which has the potential to supplant fluoroscopy, or perhaps replace it in the long term, is magnetic resonance imaging (MRI). MRI does not use ionizing radiation and does not require catheterization to image vasculature. MRI contrast agents, which are often necessary for best resolution, are much less nephrotoxic than iodinated fluoroscopy agents and are effective when administered intravenously. Web site: http://www.delphion.com/details?pn=US06574497__ •

Polyamine analogues as therapeutic and diagnostic agents Inventor(s): Bergstrom; Donald E. (3416 Hamilton St., West Lafayette, IN 47906), Burns; Mark R. (226 NW. 184th St., Shoreline, WA 98177), O'Day; Christine L. (4404-B 216th St., SW., Mountlake Terrace, WA 98043), Vermeulin; Nicolaas M. J. (19334 - 196th Ave., NE., Woodinville, WA 98072), Webb; Heather K. (5705 Seaview Ave., NW., Seattle, WA 98107) Assignee(s): None Reported Patent Number: 6,646,149 Date filed: May 31, 2000 Abstract: Novel "bispolyamine" inhibitor compounds of polyamine transport are disclosed. These compounds are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. These compounds display desirable activities both for diagnostic and research assays and therapy. Excerpt(s): The invention in the field of chemistry and biochemistry relates to the synthesis and use of novel polyamine transport (PAT) inhibitor compounds with pharmacological or agricultural uses and as probes for biochemical assays or for purification of selected polyamine binding targets. As drugs, these compounds are used to treat disorders of undesired cell proliferation, primarily cancer, alone or combined with other agents such as polyamine synthesis inhibitors. The invention also relates to the synthesis and use of such novel polyamine compounds as part of combinatorial libraries. These libraries are used to discover compositions that inhibit PAT and/or that bind to a cellular polyamine transporter (PATr). Various members of these libraries or compounds discovered through use of the libraries have utility as drugs, agricultural chemicals, and as probes. Decades of research on the myriad of biological activities that the polyamines, putrescine, spermidine and spermine play in cellular processes have shown the profound role they play in life (Cohen, S. S., "A Guide to the Polyamines" 1998, Oxford University Press, New York). As polycations at physiological pH, they bind tightly to and strongly modulate the biological activities of all of the anionic cellular components. Specific and strong interactions have been associated with DNA

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and RNA together with their associated chromatin proteins (Tabor, H. et al. 1,4Diaminobutrane (putrescine), spermidine, and spermine. Ann Rev. Biochem. 1976, 45, 285-306; Matthews, H. R. Polyamines, chromatin structure and transcription. BioEssays, 1993, 15, 561-566). Spermine has been shown to function directly as a free radical scavenger that protects DNA from insults by reactive oxygen species (Ha, H. C. et al. Proc. Natl. Acad. Sci. USA, 1998, 95, 11140-11145). Specific interactions of multicationic polyamines with microtubules has been recently shown (Wolff, J. Promotion of Microtubule Assembly by Oligocations: Cooperativity between Charged Groups. Biochemistry, 1998, 37, 10722-10729; Webb, H. K. et al., J. Med. Chem. 1999, in press). Allosteric regulation of membrane-bound enzymes including acetylcholinesterase has been shown (Kossorotow, A. et al. Regulatory effects of polyamines on membranebound acetylcholinesterase. Biochem. J. 1974, 144, 21-27). Polyamines have a direct influence on many neurotransmitter receptors and ion channels (Carter, C. The Neuropharmacology of Polyamines, 1994, Academic Press, San Diego, Calif.; Williams, K. Interaction of polyamines with ion channels, Biochem. J., 1997, 325, 289-297). Specific polyamine binding sites have also been demonstrated for the NMDA receptor complex (Ransom, R. W. et al. Cooperative modulation of [.sup.3 H]MK-801 Binding to the NMethyl-D-Aspartate Receptor-Ion Channel Complex by L-Glutamate, Glycine, and Polyamines. J. Neurochem. 1988, 51, 830-836; Williams, K. et al. Minireview: Modulation of the NMDA receptor by polyamines. Life Sci. 1991, 48, 469-498). Web site: http://www.delphion.com/details?pn=US06646149__ •

Prevention of in-stent thrombosis and complications after arterial angioplasty with stent placement using magnesium Inventor(s): Kaul; Sanjay (Northridge, CA), Shah; Prediman K. (Los Angeles, CA) Assignee(s): Cedars-sinai Medical Center (los Angeles, Ca) Patent Number: 6,692,772 Date filed: July 18, 2001 Abstract: Treatment with magnesium produces a inhibition of acute stent thrombosis under high-shear flow conditions without any hemostatic or significant hemodynamic complications. Excerpt(s): This invention relates to methods of treating thrombosis, and more particularly to the use of magnesium to prevent conditions such as in-stent thrombosis. Coronary artery disease is one of the country's largest health concerns. According to the American Heart Association, this disease affects 13.5 million Americans. Almost a million of these people have experienced heart attacks. Still others have experienced angina, undergone coronary artery bypass surgery and/or had heart transplants. Others in the later, or more severe, stages of coronary artery disease are in varying stages of congestive heart failure. Coronary artery disease, which has been linked with the increase in cholesterol and saturated fat in our diets, is treatable. One main symptom of coronary artery disease is the deposit of these fatty materials alongside a vessel wall such as an arterial wall. This results in the progressive narrowing of the lumen, and arteriosclerosis. Such deposits may be treated through a procedure called angioplasty. During angioplasty, the doctor inserts a catheter into an artery, typically a groin artery, and maneuvers the catheter up through the artery until the catheter is positioned at the site of the narrowing or obstruction caused by plaque. The plaque may then be flattened by inflating a balloon located around the tip of the catheter. As the balloon expands, it compresses the fatty deposits against the walls of the artery.

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Web site: http://www.delphion.com/details?pn=US06692772__ •

Puncture resistant balloon for use in carotid artery procedures and methods of use Inventor(s): Parodi; Juan Carlos (Buenos Aires, AR) Assignee(s): Arteria Medical Science, Inc. (san Francisco, Ca) Patent Number: 6,582,396 Date filed: March 20, 2000 Abstract: Methods and apparatus are provided for removing emboli during an angioplasty, stenting, or surgical procedure comprising apparatus for occluding the external carotid artery to prevent reversal of flow into the internal carotid artery during carotid stenting, the apparatus further comprising a wedge or capsule configured to reduce the risk of potentially dangerous interaction with the stent during retrieval. Excerpt(s): This invention relates to apparatus and methods for occluding a body lumen. More particularly, the present invention provides a puncture resistant balloon for occlusion of the external carotid artery during stenting of the internal carotid artery. Carotid artery stenoses typically manifest in the common carotid artery, internal carotid artery or external carotid artery as a pathologic narrowing of the vascular wall, for example, caused by the deposition of plaque, that inhibits normal blood flow. Endarterectomy, an open surgical procedure, traditionally has been used to treat such stenosis of the carotid artery. In view of the trauma and long recuperation times generally associated with open surgical procedures, considerable interest has arisen in the endovascular treatment of carotid artery stenosis. In particular, widespread interest has arisen in transforming interventional techniques developed for treating coronary artery disease, such as stenting, for use in the carotid arteries. Such endovascular treatments, however, are especially prone to the formation of emboli. Web site: http://www.delphion.com/details?pn=US06582396__

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Segmented balloon catheter blade Inventor(s): Radisch, Jr.; Herbert R. (San Diego, CA) Assignee(s): Scimed Life Systems, Inc. (maple Grove, Mn) Patent Number: 6,632,231 Date filed: August 23, 2001 Abstract: A device for incising a stenosis in the vasculature of a patient includes a plurality of blades mounted on a resilient base member. The blades are arranged in a pattern to allow for relative movement between adjacent blades. Specifically, at least one end portion of each blade is juxtaposed with an end portion of the next closest blade. The base member, in turn, is mounted on the external surface of an inflatable angioplasty balloon. When the balloon is inserted into the vasculature of a patient, positioned across a stenosis and subsequently inflated, the individually moveable blades form an effective cutting edge that conforms to the surface of the stenosis to effectively allow the stenosis to be incised to a substantially uniform depth. Excerpt(s): The present invention relates generally to medical devices. More particularly, the present invention pertains to invasive surgical devices which are useful for the incision and dilation of a stenosis in the vasculature of a patient. The present invention

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is particularly, though not exclusively, useful for incising a stenosis with a balloon catheter blade to facilitate subsequent dilation of the stenosis. The blockage of human arteries can lead to a variety of serious medical complications. This is so because arterial blockages reduce blood flow through the affected artery and may result in damage to the tissue that is relying on the blood supply. For example, if the blockage is in an artery which supplies blood to the heart itself, a heart attack may result. Such arterial blockages, which are also called stenoses, are typically caused by the build-up of atherosclerotic plaque on the inside wall of an artery. In fact, several such stenoses may occur contiguously within a single artery. This can result in a partial, or even complete, blockage of the artery. As a result of the danger associated with such a blockage, several methods and procedures have been developed to treat stenoses. One such method is an angioplasty procedure which uses an inflatable balloon to dilate the blocked artery. A typical inflatable angioplasty device, for example, is disclosed in U.S. Pat. No. 4,896,669 which issued to Bhate et al. for an invention entitled "DILATION CATHETER". The Bhate et al. angioplasty device includes an inflatable angioplasty balloon which is insertable into a peripheral artery of a patient for positioning across a stenosis. Once positioned, the angioplasty balloon is then inflated to flatten the stenosis against the inside wall of the artery thereby improving the blood flow through the artery. Web site: http://www.delphion.com/details?pn=US06632231__ •

Stent coating Inventor(s): Smith; Scott R. (Chaska, MN), Stanslaski; Joel L. (New Hope, MN), Wang; Lixiao (Maple Grove, MN), Yang; Dachuan (Plymouth, MN) Assignee(s): Scimed Life Systems, Inc. (maple Grove, Mn) Patent Number: 6,569,195 Date filed: June 18, 2001 Abstract: A stent having a polymeric coating for controllably releasing an included active agent. The polymeric coating includes a blend of a first polymeric material, which if alone, would release the agent at a first, higher rate, and a second polymeric material, which if alone would release the agent at a second, lower rate over a longer time period. One stent coating utilizes a faster releasing hydrophilic polymeric material and a slower releasing hydrophobic material. One stent coating includes a blend of a faster releasing PLA-PEO copolymer and a slower releasing PLA-PCL copolymer. One active agent is Taxol. One use of the Taxol delivering stent is to inhibit restenosis following angioplasty. Excerpt(s): The present application is generally related to medical devices. More specifically, the present invention relates to stent coatings capable of releasing agents over time. In particular, the present invention includes a blend of two co-polymers adapted to release restenosis-inhibiting agents over a sustained time period. Vascular disease is a leading cause of death and disability in the developed world. In the United States, more than half of all deaths are due to cardiovascular disease. Atherosclerosis is the most common form of vascular disease and leads to insufficient blood supply to body organs, which can result in hearts attacks, strokes, and kidney failure. Atherosclerosis is a form of vascular injury in which the vascular smooth muscle cells in the artery wall undergo hyperproliferation and invade and spread into the inner vessel lining, which can make the vessels susceptible to complete blockage when local blood clotting occurs. This can lead to death of the tissue served by that artery. In the case of a coronary artery, this blockage can lead to myocardial infarction and death. Coronary

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artery blockage can be treated with coronary artery bypass surgery and/or angioplasty. Both procedures may initially appear to be successful, but can be in effect undone by the effect of restenosis, or the recurrence of stenosis after such a treatment. Restenosis is believed to include hyperproliferation of vascular smooth muscle cells. In particular, about one third of patients treated using angioplasty have restenosis and blockage within 6 months after the procedure. Web site: http://www.delphion.com/details?pn=US06569195__ •

Stent delivery system Inventor(s): Hosny; Ayman A. (2222 East St., #260, Concord, CA 94520) Assignee(s): None Reported Patent Number: 6,676,691 Date filed: March 28, 2001 Abstract: A stent delivery system including a stent unit having a first portion and second portion which are contiguous with one another. The first and second portions are expandable through angioplasty balloons. The first portion is constructed with a recess in its collapsed position to hold the second portion. The second portion extends or protracts from the first portion to allow the stent to deploy in a bifurcated vessel. The stent may be employed with a delivery sheath that has separable portions. Excerpt(s): The present invention to a novel stent delivery system in the treatment of occluded blood vessels. Percutaneous transluminal coronary angioplasty (PTCA) has proven to be a successful technique in the treatment of stenotic arteries and vessels, particularly those found in the human heart. In fact in certain cases, this treatment has served as a substitute for coronary by-pass surgery. During PTCA procedures, a catheter is inserted through a large artery in the leg or arm of the patient and is directed into an occluded vessel, such as a coronary artery. The catheter also carries an inflatable balloon which forces open the obstruction, normally in the form of a plaque material. In addition to the use of such balloon angioplasty procedures, stents have been developed to maintain the dilated vessel in an open condition. The use of stents has prevented subsequent closures of vessels referred to as "restenosis", due to scarring, the accumulation of plaque and the like. A particularly vexing situation occurs in vessels which include a branching arrangement. Such situation is referred to as a bifurcating vessel, i.e. where a main trunk vessel meets a side branch vessel. The angle between the main trunk vessel and the side branch is usually referred to a "carina". Carinas may be acute, orthogonal, or obtuse. In a bifurcating vessel situation, the side branch often includes lesions similar to that of the main trunk branch. Insertion of a stent in the main trunk vessel alone, following dilation, is not satisfactory, since the side branch lumen is blocked. Stents must be placed in the main trunk vessel as well as the side branch to properly rectify occluded vessels in a bifurcating vessel. Web site: http://www.delphion.com/details?pn=US06676691__

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Stent for angioplasty and a production process therefor Inventor(s): Chinaglia; Benito (Turin, IT), Curcio; Maria (Saluggia, IT), Rolando; Giovanni (Chivasso, IT), Vallana; Franco (Turin, IT) Assignee(s): Sorin Biomedica Cardio S.p.a. (saluggia, It) Patent Number: 6,645,243 Date filed: January 8, 1998 Abstract: The stent for angioplasty has a body in the form of a generally tubular casing capable of being dilated in use from a radially-contracted position to a radiallyexpanded position. The body includes a support structure made from a first material capable of withstanding this dilation without losing its structural integrity. A structure made from a second material which has been rendered radioactive following the exposure of the stent itself to a neutron flux is associated with at least a portion of the carrying structure. Excerpt(s): The present invention generally concerns so-called stents for angioplasty. The term "stent" is intended generally to indicate devices intended for endoluminal application (for example, within a blood vessel) usually effected by catheterisation, with the subsequent expansion in place for the local support of the lumen. The principal aim of this is to avoid the re-establishment of a stenotic site at the treated site. It should be noted that the use of substantially similar structures to effect the expansion and anchorage in place of vascular grafts has already been proposed in the art: naturally, this possible extension of the field of application should also be seen as being included within the ambit of the invention. For a general review of vascular stents, reference may usefully be made to the work "Textbook of Interventional Cardiology" edited by Eric J. Topol, W. B. Saunders Company, 1994 and, in particular, to section IV of volume II, entitled "Coronary stenting". Web site: http://www.delphion.com/details?pn=US06645243__

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System and methods for catheter procedures with circulatory support in high risk patients Inventor(s): Macoviak; John A. (La Jolla, CA), Samson; Wilfred J. (Saratoga, CA) Assignee(s): Cardeon Corporation (cupertino, Ca) Patent Number: 6,673,040 Date filed: August 27, 1999 Abstract: A system and methods are described for performing catheter based procedures on high risk patients that mitigate the risk to the patient and extend the acceptable time window for response when emergencies or complications arise. The system is useful for stopped heart catheter procedures or as a safety backup in beating heart catheter procedures and is compatible with concurrent or sequential surgical interventions. The system combines a therapeutic or diagnostic catheter subsystem with a selective aortic perfusion and cardiopulmonary bypass subsystem. The catheter subsystem may include catheters for angioplasty, stent delivery, atherectomy, valvuloplasty or other diagnostic or therapeutic procedures. The selective aortic perfusion and cardiopulmonary bypass subsystem generally includes catheters and/or cannulas for draining blood from the patient's venous or arterial system, a perfusion pump, a blood oxygenator, at least one blood heat exchanger and catheters and/or

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cannulas for perfusing oxygenated blood into the patient's arterial system. The arterial perfusion catheters and/or cannulas are constructed with an upstream flow control member located in the patient's ascending aorta and a downstream flow control member located in the patient's descending aorta. The external flow control members may take the form of inflatable occlusion balloons and/or selectively deployable external catheter flow control valves. The external flow control members may be mounted on a single elongated catheter or cannula shaft or they may be mounted on separate catheter or cannula shafts for independent placement and deployment. Excerpt(s): The present invention relates generally to cardiovascular catheters and also to circulatory support systems. More particularly, it relates to a system and method for performing catheter based medical procedures, such as balloon angioplasty, stent placement, atherectomy, valvuloplasty and other therapeutic procedures, with protective circulatory support in order to minimize the risk to the patient from such procedures. The system and methods of the present invention serve to expand the patient population treatable by catheter based procedures to include patients who might otherwise require open chest surgery with cardiopulmonary bypass and also to high risk patients who might not be acceptable candidates for these surgical alternatives. Many catheter based diagnostic and therapeutic procedures have been developed in the areas of interventional cardiology, interventional radiology, interventional neuroradiology and electrophysiology. Examples of such procedures include balloon angioplasty, stent placement, atherectomy and valvuloplasty. These and many other catheter based diagnostic and therapeutic procedures can benefit from the system and methods of the present invention, particularly in high risk patients. Balloon angioplasty is a procedure in which a small, cylindrical balloon is mounted on an elongated catheter which is inserted into a stenosis or a narrowing in a blood vessel and inflated to dilate the stenosis and improve blood flow. Balloon angioplasty can be applied to coronary arteries, carotid arteries and peripheral arteries, as well as other body passages. Patents which describe apparatus and methods for performing balloon angioplasty include U.S. Pat. Nos. 4,195,637; 4,323,071; 4,545,390; 4,545,390; 4,538,622; 5,055,024; 4,490,421; 4,616,653; 5,133,364; 5,060,660; 5,031,636; 4,922,923; 4,917,103; 4,875,489; 4,827,941; 4,762,129; 4,988,356; 4;748;982; 5,040,548 and 5,061,2,73. The specifications of these patents and all other patents and patent applications mentioned herein are hereby incorporated by reference in their entirety. Web site: http://www.delphion.com/details?pn=US06673040__ •

Therapeutic coating for an intravascular implant Inventor(s): Jayaraman; Swaminathan (459 Lowell Pl., Fremont, CA 94536) Assignee(s): None Reported Patent Number: 6,641,611 Date filed: November 26, 2001 Abstract: The invention relates to a coating for an intravascular implant that prevents hyperproliferative vascular disease after a mechanical injury, such as angioplasty. The coating includes first and second agents, with the first agent acting on a calcium independent cellular pathway and the second agent acting on a calcium dependent cellular pathway. In an exemplary embodiment, the first agent is rapamycin and the second agent is cyclosporine A. The agents can be incorporated in a polymeric agent and can be applied either directly to the implant or on top of a primer layer placed on the implant. A top coat can be applied to the therapeutic coating, if desired.

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Excerpt(s): The present invention relates to a therapeutic coating for an intravascular implant, and in particular to a coating that prevents or treats hyperproliferative vascular disease including intimal smooth muscle cell hyperplasia, restenosis, and vascular occlusion. As discussed in more detail below, the prior art discloses many examples of therapeutic coatings that have been applied to intravascular devices. The objective behind applying the therapeutic coating is to either mediate or suppress a tissue response at the site of implantation. For example in intravascular situations, one of the obvious outcomes of implanting a foreign body is for an intense reaction at the site of implantation. This intense reaction can result from either the implantation itself or the stresses generated after implantation. Due to the reaction, there is an obvious interaction by the vessel wall to compensate for this injury by producing a host of tissue related responses that is generally called "healing due to injury." It is this healing process that the therapeutic coating attempts to mediate, suppress, or lessen. In some instances, this healing process is excessive in which it occludes the entire lumen providing for no blood flow in the vessel. This reoccluded vessel is also called a resteinotic vessel. Therapeutic coatings can behave in different ways. For example, depending upon the kind of therapeutic agent used, the various cellular levels of mechanisms are tackled. Some of the therapeutic agents act on the growth factors that are generated at the site of implantation or intervention of the vessel. Some other therapeutic agents act on the tissues and suppress the proliferative response of the tissues. Others act on the collagen matrix that comprises the bulk of the smooth muscle cells. Some examples of prior art relating to therapeutic coatings follow. Web site: http://www.delphion.com/details?pn=US06641611__ •

Treating metal surfaces to enhance bio-compatibility and/or physical characteristics Inventor(s): Al-Lamee; Kadam Gayad (Leeds, GB), Taktak; Yousef Samih (Matlock, GB) Assignee(s): Polybiomed Limited (gb) Patent Number: 6,599,558 Date filed: December 2, 1999 Abstract: A metal, glass or ceramics surface is treated to enhance its compatibility with biological material such as blood or blood related products. Treatment involves covalently bonding to the surface by means of a catalyst functional molecules each of has at least one alkoxysilane group which can form at least one first covalent bond by reaction with the oxide or hydroxide of said surface and at least one other group which can participate in free-radical polymerisation. Free-radical polymerisation from said functional molecules is then effected to build bio-compatible and/or hydrophilic polymer chains. The compatibility of the metal surface with biological material may be further improved by bonding bio-active molecules, such as heparin or heparin derived molecules to the polymer chains. Suitable metal surfaces are those of medical devices such as heat exchangers, coronary and peripheral stents and guide wires used in angioplasty. In the case of a stent, restenosis may be inhibited by incorporating into the coating a radio-labelled compound, foe example radio-labelled heparin and/or by incorporating a compound that inhibits cell proliferation e.g. mitoxantrone. Excerpt(s): The present invention relates to a method of treating metal surfaces to enhance the bio-compatibility and/or physical characteristics of said surfaces. The invention also relates to bio-compatible metal articles. The invention is particularly relevant to surfaces of medical devices. Many medical techniques are known in which human or animal blood is brought into contact with foreign surfaces, either within the

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body or outside the body. In some situations, usually due to mechanical characteristics, it is necessary to use metallic surfaces, as required by coronary stents (vascular endoprostheses) located within arteries or, for example, within heat exchanger assemblies external to the body. Thus, in the first application, the mechanical strength of the metal object is required whereas in the external application it is the heat transfer characteristics that are required. However, in both applications, blood or related blood products are brought into contact with metal surfaces, which may in turn have detrimental effects upon the blood itself. Heparin is a naturally occurring substance that consists of a polysaccharide with a heterogeneous structure and a molecular weight ranging from approximately 6000 to 30000 Dalton (atomic mass units). It prevents uncontrolled clotting by suppressing the activity of the coagulation system through complexing with antithrombin (III), whose activity it powerfully enhances. Approximately one in three heparin molecules contains a sequence of highly specific structures to which antithrombin binds with high affinity. When bound to the specific sequence, the coagulation enzymes are inhibited at a rate that is several order of magnitude higher than in the absence of Heparin. Thus, the heparin molecule is not in itself an inhibitor but acts as a catalyst for natural control mechanisms without being consumed during the anticoagulation process. The catalytic nature of heparin is a desirable property for the creation of a bio-active surface, because the immobilised heparin is not functionally exhausted during exposure to blood but remains a stable active catalyst on the surface. Web site: http://www.delphion.com/details?pn=US06599558__ •

Ultrasonic angioplasty transmission wire Inventor(s): Cornish; Wayne E. (Fallbrook, CA), Gesswein; Douglas H. (Temecula, CA) Assignee(s): Advanced Cardiovascular Systems, Inc. (santa Clara, Ca) Patent Number: 6,589,253 Date filed: December 30, 1999 Abstract: The ultrasonic angioplasty transmission wire for use in an ultrasonic angioplasty device comprises an inner layer of a first ultrasound transmitting material, and at least one outer coaxial shell or tube of a second ultrasound transmitting material different from the first ultrasound transmitting material. The first inner layer and one or more of the outer coaxial shells or tubes can be formed of ultrasound transmitting metal compositions such as stainless steel, nickel-titanium, or aluminum, or other similar suitable ultrasound transmitting metals. In one embodiment, the first inner layer is formed of a nickel-titanium alloy, and at least one outer coaxial shell or tube is formed of stainless steel. In another embodiment, the first inner layer is formed of nickeltitanium alloy, a first outer coaxial shell or tube is formed of stainless steel, and a second outer coaxial shell or tube is formed of the nickel-titanium alloy. Excerpt(s): This invention relates generally to medical devices, and more particularly concerns an improved ultrasound transmission member for use in an ultrasonic catheter for treatment of blockages of hollow anatomical structures. In typical percutaneous transluminal coronary angioplasty (PTCA) procedures, a guiding catheter having a preformed distal tip is percutaneously introduced into the cardiovascular system of a patient through the brachial or femoral arteries and is advanced therein until the distal tip thereof is in the ostium of the desired coronary artery. A guide wire and a dilatation catheter having a balloon on the distal end thereof are introduced through the guiding catheter with the guide wire slidably disposed within an inner lumen of the dilatation

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catheter. The guide wire is first advanced into the patient's coronary vasculature until the distal end thereof crosses the lesion to be dilated and then the dilatation catheter is advanced over the previously introduced guide wire until the dilatation balloon is properly positioned across the lesion. The balloon may then be inflated to treat the lesion. Thereafter, a stent device may be located at the treated lesion, if deemed necessary. In "ultrasonic" angioplasty, an ultrasonic angioplasty catheter is similarly advanced to an area of vascular blockage, and mechanical vibration at ultrasonic frequencies, generated typically by a piezoceramic transducer, is delivered along an ultrasonic angioplasty transmission member or wire to a distal catheter tip. When the distal catheter tip is abutted against intravascular blockage, the vibration of the distal end of the ultrasonic angioplasty transmission member removes the obstruction by mechanical impact and cavitation. Web site: http://www.delphion.com/details?pn=US06589253__

Patent Applications on Angioplasty 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 angioplasty: •

1,3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders Inventor(s): Hoong, Lee K.; (Suwanee, GA), Meng, Charles Q.; (Alpharetta, GA), Ni, Liming; (Duluth, GA), Sikorski, James A.; (Alpharetta, GA) Correspondence: King & Spalding; 191 Peachtree Street, N.E.; Atlanta; GA; 30303-1763; US Patent Application Number: 20030236298 Date filed: May 21, 2003 Abstract: It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-one- s, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, postangioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Excerpt(s): This application is a continuation U.S. Ser. No. 09/886,348, filed Jun. 20, 2001, which claims priority to U.S. S. No. 60/212,769, filed on Jun. 20, 2000, and U.S. S. No. 60/255,934 filed on Dec. 15, 2000, the disclosures of which are hereby incorporated by reference in their entirety. The present invention includes novel heteroaryl or heterocyclic 1,3-bis-(substituted-phenyl)-2-propen-1-ones as well as methods and compositions for the treatment of disorders mediated by VCAM-1 or MCP-1 and for the

10

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

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treatment of inflammatory disorders generally that include the administration of a 1,3bis-(substituted-phenyl)-2-propen-1-one that has at least one phenyl substituent that is an aryl, heteroaryl or heterocyclic moiety. Adhesion of leukocytes to the endothelium represents a fundamental, early event in a wide variety of inflammatory conditions, autoimmune disorders and bacterial and viral infections. Leukocyte recruitment to endothelium is mediated in part by the inducible expression of adhesion molecules on the surface of endothelial cells that interact with counterreceptors on immune cells. Endothelial cells determine which types of leukocytes are recruited by selectively expressing specific adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. VCAM-1 binds to the integrin VLA-4 expressed on lymphocytes, monocytes, macrophages, eosinophils, and basophils but not neutrophils. This interaction facilitates the firm adhesion of these leukocytes to the endothelium. VCAM-1 is an inducible gene that is not expressed, or expressed at very low levels, in normal tissues. VCAM-1 is upregulated in a number of inflammatory diseases, including arthritis, asthma, dermatitis, psoriasis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Acetamide derivatives and the use thereof as inhibitors of coagulation factors xa and viia Inventor(s): Barnes, Christopher; (Bad Soden, DE), Dorsch, Dieter; (Ober-Ramstadt, DE), Gleitz, Johannes; (Darmstadt, DE), Juraszyk, Horst; (Seeheim-Jugenheim, DE), Mederski, Werner; (Erzhausen, DE), Tsaklakidis, Christos; (Weinheim, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030187037 Date filed: January 29, 2003 Abstract: Novel compounds of the formula I, in which R, R.sup.1 and R.sup.2 are as defined in patent claim 1, are inhibitors of coagulation factor Xa and VIIa and can be employed for the treatment of thromboses, myocardial infarction, arteriosclerosis, inflammation, apoplexis, angina pectoris, restenosis after angioplasty, claudicatio intermittens, tumours, tumour diseases and/or tumour metastases. Excerpt(s): and pharmaceutically tolerated salts, solvates and stereoisomers thereof. The invention also relates to the optically active forms, the racemates, the diastereomers and the hydrates and solvates, for example alcoholates, of these compounds. The invention had the object of finding novel compounds having valuable properties, in particular those which can be used for the preparation of medicaments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 169

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Angioplasty balloon with thin-walled taper and method of making the same Inventor(s): Lee, Jeong S.; (Diamond Bar, CA) Correspondence: James C. Scheller, JR.; Blakely, Sokoloff, Taylor & Zafman Llp; Seventh Floor; 12400 Wilshire Boulevard; Los Angeles; CA; 90025-1026; US Patent Application Number: 20030139762 Date filed: February 3, 2003 Abstract: An angioplasty balloon and method of manufacture are provided. The balloon has a working length and a taper each having a substantially equivalent thickness. This allows the balloon to be steered easily through vasculature to the site of a stenosis prior to inflation during an angioplasty procedure. The taper thickness in particular is achieved through use of a specially designed multi-tubular slug which is molded to form the angioplasty balloon of the present invention. Excerpt(s): This invention relates generally to dilation catheters. More particularly, the invention relates to intravascular angioplasty catheter balloons and a method of manufacturing the same. Angioplasty is a procedure by which stenotic lesions (atheromatous deposits), found in cases of atherosclerosis. During angioplasty, a guidewire is inserted into the cardiovascular system, generally via the femoral artery under local anesthesia. The guidewire is advanced through the patient's vasculature to the site of the stenosis (stenotic lesion). Placement of the guidewire may be aided by way of fluoroscopic observation. A dilatation catheter, having a guidewire lumen and distensible balloon portion, is then advanced through the vasculature until the balloon portion, at the distal end of the catheter, traverses or crosses a stenotic lesion. The artery is narrowed in the area of the stenotic lesion due to the atheromatous deposits occupying arterial space at the walls of the artery. Once placed, the balloon portion of the catheter is inflated, generally with a fluid, to compress the atheromatous deposits against the walls of the artery. This compression dilates the lumen of the artery leaving an unblocked arterial passage once the guidewire and catheter are removed. Looking back to where the uninflated balloon encounters the stenosis, it must first cross at least a portion thereof in order to reach its distal-most destination. Therefore, a flexible, low profile balloon is preferable. In particular, the ends of the uninflated balloon should taper smoothly and lay low so that the balloon can be threaded into tight passages. It is preferable that the thickness of the balloon material be substantially constant from a working length throughout each taper. In the present context, a thick wall is at least approximately 0.002" in thickness while a thin wall is approximately 0.001" in thickness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Angioplasty device with embolic recapture mechanism for treatment of occlusive vascular diseases Inventor(s): Divani, Afshin A.; (Buffalo, NY), Qureshi, Adnan I.; (Buffalo, NY) Correspondence: David L. Principe; Hodgson Russ Llp; One M&t Plaza, Suite 2000; Buffalo; NY; 14203-2391; US Patent Application Number: 20040006307 Date filed: July 2, 2002 Abstract: An angioplasty device with emboli pull-in mechanism is provided that includes an infusion catheter with a proximal end and a distal end. A balloon catheter

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having an inflatable cavity formed by an inner wall and an outer wall is disposed coaxially with the infusion catheter. The balloon catheter has a proximal end and a distal end. The distal end of the balloon catheter is sealingly attached to the infusion catheter. And the balloon catheter has at least one communicating channel disposed from the outer wall to the inner wall of the balloon catheter. A suction catheter is disposed between the balloon catheter and the infusion catheter. The suction catheter is in fluid communication with the at least one communicating channel in the balloon catheter. Excerpt(s): The present invention relates to a medical device suitable for use in intravascular angioplasty. Release of atherosclerotic debris is the primary cause of ischemic events such as stroke or myocardial infarction during a routine intravascular angioplasty. A standard balloon inflates and deflates via the change in pressure induced by contrast material and saline. The balloon provides a radial force to the surrounding vessel wall resulting in dilation of occlusive lesions in the vessel wall. The process nevertheless releases debris from the site of angioplasty that can migrate distally with the blood flow to occlude small blood vessels resulting in catastrophic outcomes. While the balloon is completely inflated, the loosened plaque particles are compressed against the vessel wall. However, once the balloon is deflated, the plaque particles can move freely with the blood stream into the distal vasculature and embolize arteries of various sizes. Plaque particles of 100 micron or larger can occlude small and medium size vessels. Conventional angioplasty balloons cannot provide protection against debris generated during an angioplasty procedure. In recent years, the use of an embolic protection device is suggested to capture embolic debris during angioplasty. Distal protection devices, such as filters, are under investigation to be placed distal to site of occlusion to block the passage of particles. Different devices are introduced to the market with various degrees of success in capturing plaque particles. However, the use of new embolic protection devices requires insertion and position of the device into the artery distal to the angioplasty site. In many cases the lumen of the artery at the atherosclerotic site is reduced to a point that passage of any extra device is difficult. Furthermore, tortuosity and angulation of the distal vessels prevent successful placement of protection devices. What is needed is a balloon that can perform angioplasty and at the same time prevent the release of embolic debris. The present invention meets the above-described need by providing an angioplasty device having a balloon catheter with an embolic recapture mechanism that does not require deployment of a trap located beyond the balloon catheter in the distal direction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Angioplasty super balloon fabrication with composite materials Inventor(s): Jimenez, Oscar; (Coral Gables, FL) Correspondence: Thomas R. Vigil; C/o Welsh & Katz, LTD.; 22nd Floor; 120 South Riverside Plaza; Chicago; IL; 60606; US Patent Application Number: 20030143350 Date filed: January 14, 2002 Abstract: The balloon catheter comprises a plastic tubing, a balloon fused to one end portion of said tubing, and the balloon being made of a polymer and one of a carbon nano-tube material, a nano-clay material or a nano-ceramic fiber material. Excerpt(s): The present invention relates to reinforced balloons and to several methods for creating composite films of organic polymers and inorganic additives on a

Patents 171

nanometric scale which are compounded with polymers to be used to form angioplasty ballons to increase their strength. The super balloons or reinforced balloons are created with carbon nanotubes, clay platelets or ceramic, e.g. alumina, fibers which are included in the balloon material with a polymer. Angioplasty balloons are required to be able to withstand very high pressures, which force the balloons surface against various vessel tissues and deposits representing a range of viscoelastic characteristics, and include some very hard and rough surfaces. As the balloons must be thin-walled to collapse into a small profile (cross-section) for introduction to the target area, the balloons must be made extremely strong and puncture resistant. The balloons also must expand in a predictable manner when the internal pressure is beyond the nominal value where the cross-section is rated. In addition, balloon catheters are also used to deploy metallic stents within a constricted vessel. Stents are expandable wire or flat metal mesh devices that help retain proper vessel lumen after dilation. In this application, the balloon must come in contact with a metallic mesh that may inflict damage to the balloon. To meet these exacting requirements the present invention teaches several methods of creating composite films of organic polymers and inorganic additives, including carbon nanotubes, nanoclays, and ceramic, alumina, fibers on a nanometric scale. The invention is also directed at the preparation and formation of balloons using specifically carbon nanotubes, clay platelets and ceramic fibers. Angioplasty addresses the problems related to partially or fully obstructed blood vessels. Angioplasty balloons have been used by invasive cardiologists since the 1970s when Andreas Grunzig reported his data on reopening the occluded coronary arteries of five patients and that these arteries remained patent, open, allowing blood flow for six months or longer. The Grunzig procedure involved the introduction of a high-pressure angiographic catheter with a deflated or collapsed polymer balloon attached to its distal portion. Once the catheter is positioned within the occluded range (lesion) in the artery under fluoroscopic control, the balloon is pressurized, typically by injecting a fluid. The pressure in the balloon exerts pressure on the surrounding obstructive structures and enlarges the lumen, which results in an increase in blood flow. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apparatus for trapping emboli Inventor(s): Ladd, William Gregory; (Williamsport, TN) Correspondence: Medtronic Ave, INC.; 3576 Unocal Place; Santa Rosa; CA; 95403; US Patent Application Number: 20040006364 Date filed: April 1, 2003 Abstract: A filter for filtering micro-emboli from a patient's blood during an angioplasty procedure is disclosed which comprises a plurality of curved wires connected to a rod between a first connector fixed with respect to the rod and a second connector slidingly mounted on the rod. Two layers of filter material are connected to opposite sides of the wires, and each layer includes perforations which are offset from the perforations in the other layer. When the rod and the wires are disposed within a catheter, the inner wall of the catheter compresses the wires toward the rod and when the rod is extended from the catheter, the wires resume their curved shape and pull the sliding connector along the rod toward the fixed connector. Excerpt(s): This application is a continuation-in-part of application Ser. No. 867,531 filed Jun. 2, 1997, and converted into a provisional application on Aug. 13, 1997. The present application is directed toward a filter, and more specifically, toward a filter for use

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during a catheterization procedure for filtering blood downstream of the procedure site. Arteriosclerosis is a condition in which plaques develop on the inner walls of blood vessels and restrict the flow of blood therethrough. Organs downstream of this constriction can be starved of oxygen, and the heart must work harder to pump blood through a circulatory system that includes such blockages. When the blockage occurs in the coronary arteries which feed the heart, a heart attack can result. Similarly, blockages in the carotid arteries can restrict the flow of blood to the brain with obvious negative consequences. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Aza-amino acid derivatives (factor Xa inhibitors 15) Inventor(s): Barnes, Christopher; (Bad Soden, DE), Dorsch, Dieter; (Ober-Ramstadt, DE), Gleiltz, Johannes; (Darmstadt, DE), Juraszyk, Horst; (Seeheim-Jugenheim, JP), Mederski, Werner; (Zwingenberg, DE), Tsaklakidis, Christos; (Weinheim, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040034072 Date filed: August 4, 2003 Abstract: The invention relates to semicarbazides of the general formula I 1where R.sup.1, R.sup.2, R.sup.3, R.sup.4 and I have the meaning indicated in claim 1.The compounds of the formula I can be employed as pharmaceutical active compounds in human and veterinary medicine, in particular for the control and prevention of thromboembolic disorders such as thrombosis, mycocardial infarct, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after angioplasty and intermittent claudication. Excerpt(s): and their pharmaceutically tolerable salts and solvates. The invention also relates to the optically active forms, the racemates, the diastereomers and also the hydrates and solvates, e.g. alcoholates, of these compounds. For the control of hemorrhages caused by injuries, the human body has a mechanism by means of which, with the aid of blood clots, a rapid wound closure is achieved. Blood clots are formed by a series of zymogen activations. In the course of this enzymatic cascade, the activated form of a factor in each case catalyzes the activation of the next. Since this process is of catalytic nature, very small amounts of the triggering factor suffice to set the cascade in motion. As a result of the large number of steps, a large amplification is achieved, which guarantees a rapid response to the injury. The plasmatic clotting after a tissue lesion can take place exogenously due to the release of tissue thrombokinase. The corresponding reaction sequence is designated as an extravascular system (extrinsic system) and proceeds within seconds. The clotting can also be triggered endogenously by thrombocytolysis. This reaction sequence, which is designated as an intravascular system, proceeds within minutes. Both systems result in a final common sequence of steps which lead to the formation of a blood clot. The intravascular and the extravascular system have a mutual influence in vivo. Both are necessary for the complete course of blood clotting. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 173

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Balloon catheter Inventor(s): Garakani, Morteza Hemmati; (Margate, FL) Correspondence: White & Case Llp; Patent Department; 1155 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20040006360 Date filed: July 3, 2002 Abstract: A balloon catheter comprises a shaft including a tubular having a relatively rigid proximal shaft section and a distal shaft section, each section connected to one another through a flexible transition member, and an inflatable balloon extending at a distal portion of the distal shaft section. The proximal and distal shaft sections define an inflation lumen extending therein which is in fluid communication with an interior of the balloon to allow inflation pressure to the balloon. The distal shaft further comprises a guide wire lumen to receive a guide wire. The guide wire lumen has a guide wire inlet, located between the end portion of the proximal shaft section and the balloon, and a guide wire outlet, located distally to the balloon and leading to an exterior of the catheter. The balloon catheter can be used for coronary angioplasty. Excerpt(s): The present invention relates to a balloon catheter comprising a shaft including a mainly tubular relatively rigid proximal shaft section and a distal shaft section, more flexible than the proximal shaft section, attached to a distal end portion of the proximal shaft section, and an inflatable balloon extending at a distal portion of the distal shaft section, the proximal and distal shaft section defining an inflation lumen extending therein which is in fluid communication with an interior of the balloon to allow inflation pressure to the balloon, the distal shaft section comprising a guide wire lumen to receive a guide wire, which guide wire lumen has a guide wire inlet, located between the end portion of the proximal shaft section and the balloon, and a guide wire outlet, located distally to the balloon and leading to an exterior of the catheter, in which a flexible transition member is attached to the distal end portion of the proximal shaft segment extending into the distal shaft segment. In particular the present invention relates to a dilatation balloon catheter of the so called "rapid exchange over-the-wire" type having a relatively short distal guide wire lumen extending through part of the distal shaft section, including the balloon area. Such a balloon catheter is widely used in the field of coronary angioplasty, particularly for percutaneous transluminal coronary angioplasty (PTCA). Angioplasty procedures have gained wide acceptance as efficient and effective methods of treating various types of vascular disease. In particular, angioplasty is widely used for opening stenosis in the coronary arteries, although it may be used for the treatment of stenosis in other areas of the body as well. The most widely used form of angioplasty requires a dilatation catheter carrying an inflatable balloon at its distal end. Typically, a hollow guide catheter is initially placed, percutaneously, in the femoral artery of the patient and is advanced along the descending aorta over the aortic arch and into the ascending aorta that leads from the heart. The distal end of the guide catheter is specially shaped so that the distal tip of the guide catheter will easily lodge in the entrance to the right or left coronary artery. This guide catheter is used in rapidly guiding the dilatation catheter through the vascular system to a position slightly beyond said entrance. Using, fluoroscopy, the physician guides the dilatation catheter the remaining distance across a strongly curved part of the trajectory through the vascular system until the balloon is positioned to cross the stenosis. The balloon is then inflated by supplying fluid under pressure through the inflation lumen extending from a proximal end of the catheter to within the balloon. The inflation of the balloon causes stretching of the artery and pressing of the lesion into the artery wall, thus

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reestablishing an acceptable blood flow through the artery. In order to be readily advanced to the place of treatment, the catheter should preferably fulfill a number of mutually opposite requirements. First of all the catheter should be pushable such that pushing forces exerted on its proximal end are really transmitted to the distal tip. Also torque forces need to be transmitted as undisturbed as possible throughout the catheter to enhance the steerability and responsiveness of the device. The transmission of these forces is served by a rigid and stiff catheter shaft. However, the catheter should also be sufficiently flexible to be able to follow the natural anatomy of the vasculature, especially the strongly curved trajectory in the coronary region, and to reach the stenosis. The latter is generally referred to as the trackability of the catheter. In order to comply with both these requirements, the balloon catheter of the kind described in the opening paragraph comprises a composite shaft design with a distal section which is sufficient flexible to comply with the natural anatomy of the coronary arteries, offering the required trackability, and with a proximal shaft section, which is more rigid to provide the required pushability and steerability. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Balloon catheter for creating a longitudinal channel in a lesion and method Inventor(s): Meyer, Steven T.; (San Jose, CA), Ogata, Wayne M.; (San Ramon, CA) Correspondence: Flehr Hohbach Test Albritton & Herbert Llp; Suite 3400; Four Embarcadero Center; San Francisco; CA; 94111-4187; US Patent Application Number: 20030153870 Date filed: February 14, 2002 Abstract: A balloon catheter for performing an angioplasty procedure on a lesion in a vessel comprising a flexible elongate catheter shaft having proximal and distal extremities. A balloon is secured to the distal extremity of the catheter shaft and has an outer surface extending between proximal and distal extremities of the balloon. A flexible elongate element is provided which extends over the outer surface of the balloon. The flexible elongate element has proximal and distal extremities which are secured about the catheter shaft in positions spaced longitudinally away from the outer surface of the balloon to permit expansion of the balloon and to cause movement of the flexible elongate element into engagement with the lesion to form a longitudinal channel in the lesion. Excerpt(s): This invention relates to a balloon catheter for creating a longitudinal channel in a lesion and a method for constructing the balloon catheter. Balloon catheters have heretofore been provided which have knives mounted on the balloon such as disclosed in U.S. Pat. Nos. 5,196,024, 5,320,634, 5,616,149 and 5,797,935. Such devices have been found to have disadvantages in that a special mounting must be provided for securing the knives to the balloon. There is a potential for such knives becoming detached from the balloon. In other embodiments, the knives are seated within longitudinal grooves provided in the balloon. Such approaches decrease the flexibility of the balloon and in addition increase the costs of construction. There is therefore a need for a new and improved balloon catheter which overcomes these disadvantages. In general, it is an object of the present invention to provide a balloon catheter for creating a longitudinal channel in a lesion and a method for making the balloon catheter. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 175

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Biphenyl derivatives and the use thereof as integrin inhibitors Inventor(s): Goodman, Simon; (Griesheim, DE), Stahle, Wolfgang; (Ingelheim, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030187289 Date filed: February 21, 2003 Abstract: Novel biphenyl derivatives of the general formula (I), in which Y, R R.sup.1, R.sup.2, R.sup.3, R.sup.4, m, o and p are as defined in claim 1, and their physiologically acceptable salts and solvates are integrin inhibitors and can be employed for combating thrombosis, cardiac infarction, coronary heart disease, arteriosclerosis, inflammation, tumours, osteoporosis, infections aid restenosis after angioplasty or in pathological processes which are maintained or propagated by angiogenesis. 1 Excerpt(s): and their physiologically acceptable salts and solvates. Partially similar compounds are disclosed in WO 95/32710. The object of the invention was to discover novel compounds having valuable properties, in particular those which are used for the preparation of medicaments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Biphenyl derivatives and the use thereof as integrin inhibitors Inventor(s): Goodman, Simon; (Griesheim, DE), Holzemann, Gunter; (SeeheimJugenheim, DE), Stahle, Wolfgang; (Ingelheim, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040010023 Date filed: February 21, 2003 Abstract: The invention relates to novel biphenyl derivatives of the general formula (I), wherein R.sup.4 represents an aromatic heterocycle, and to the physiologically acceptable salts or solvates thereof. The inventive compounds are integrin inhibitors and are used for combating thromboses, cardiac infarction, coronary heart diseases, arteriosclerosis, inflammations, tumors, osteoporosis, infections and restenosis following angioplasty or for pathological processes that are maintained or propagated by angiogenesis. 1 Excerpt(s): and their physioligically acceptable salts and solvates. Compounds which in some cases are similar are disclosed in WO 97/26250. The invention was based on the object of finding novel compounds having valuable properties, in particular those which can be used for the production of medicaments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Blood flow maintaining stent delivery system Inventor(s): Kashyap, Ravindra L.; (Brooklyn, NY) Correspondence: George Likourezos; Carter, Deluca, Farrell & Schmidt, Llp; Suite 225; 445 Broad Hollow Road; Melville; NY; 11747; US Patent Application Number: 20030220680 Date filed: February 3, 2003 Abstract: The present invention is directed to a Flow Maintaining Stent Delivery System, FMSDS, which can be used in many cardiovascular and surgical procedures, especially for placing stents into patients having stenosed and occluded arteries and other vascular lumens. It can also be used as an examination tool for the vascular surgical operations and to examine small orifice internal or external to the body. Most important, the advantage of the present stent delivery system is that it allows antegrade downstream blood flow to be maximally maintained during stenting procedures, angioplasty procedures or in any other vascular surgical operations that can use this system. The present invention also allows for uniform placement of the stent onto the artery. Excerpt(s): This patent application claims priority to a U.S. Provisional Application filed on Mar. 19, 2002 and assigned U.S. Provisional Application Serial No. 60/365,504 and to a United States Provisional Application filed on Feb. 4, 2002 and assigned U.S. Provisional Application Serial No. 60/354,188, the contents of both applications are incorporated herein by reference. The present invention relates to a medical/surgical angioplasty and stent delivery system, and also its multi-purpose use as a small retractor to virtually keep open any small orifice of the body. Many balloon stent delivery systems occlude blood flow during stenting operations. For laminar flow the equation of flow in an artery is: Q (Flow)=.DELTA.P/R.sub.f=.DELTA.P/8.eta.l/.pi.R.sup.4=.pi.R.sup.4.DE- LTA.P/8.eta.l (where.DELTA.P is change in pressure; R.sub.f is resistance;.eta. is viscosity of fluid like blood; l is length of the artery; and R is radius of the artery). Most important, in the above equation for flow, Q, derived from physical principles is proportional to R.sup.4 (R being the radius of an artery). Thus any incremental decrease or increase in the radial length R of the artery has tremendous effect on blood flow Q. So, stent delivery systems that allow for an incremental decrease in the radial lumen length of an artery will substantially impede blood flow. In particular the interruption of blood flow to the heart is so critical to patients during angioplasty and stenting operations, that the system of using balloons as delivery system may not be efficient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Convertible balloon catheter and manufacture thereof Inventor(s): Coyle, Noel; (Galway, IE), Duffy, Niall; (Galway, IE) Correspondence: Medtronic Ave, INC.; 3576 Unocal Place; Santa Rosa; CA; 95403; US Patent Application Number: 20040039409 Date filed: August 23, 2002 Abstract: A convertible balloon catheter for use as either an over-the-wire catheter or a rapid exchange catheter, comprising a flexible outer shaft, flexible inner shaft, angioplasty balloon, and bifurcate hub. The inner shaft is comprised of a relatively elastic, deformable material and forms an inflation lumen. The inner inflation shaft is

Patents 177

attached to the outer shaft, and has a cross section that is radially collapsible to increase the size of a full-length guide wire lumen formed between an outer surface of the inner shaft and an inner surface of the outer shaft. Formed in the outer shaft is a hatch, which covers a guide wire port. The hatch has a perforated peripheral edge which allows the hatch to be removed. The balloon is simply constructed with essentially four components, which significantly reduces the labor required for assembly. Excerpt(s): This invention relates generally to a medical device. More specifically, the invention relates to a balloon catheter that is convertible from an over-the-wire catheter (OTW) to a rapid-exchange (RX) catheter. Cardiovascular disease, including atherosclerosis, is the leading cause of death in the U.S. The medical community has developed a number of methods and devices for treating coronary heart disease, some of which are specifically designed to treat the complications resulting from atherosclerosis and other forms of coronary arterial narrowing. One method for treating atherosclerosis and other forms of coronary narrowing is percutaneous transluminal coronary angioplasty, commonly referred to as "angioplasty" or "PTCA". The objective in angioplasty is to enlarge the lumen of the affected coronary artery by radial hydraulic expansion. The procedure is accomplished by inflating a balloon of a balloon catheter within the narrowed lumen of the coronary artery. Radial expansion of the coronary artery occurs in several different dimensions, and is related to the nature of the plaque. Soft, fatty plaque deposits are flattened by the balloon, while hardened deposits are cracked and split to enlarge the lumen. The wall of the artery itself is also stretched when the balloon is inflated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Coronary catheter with radiopaque length markers Inventor(s): Richard, Merwin F.; (Yonkers, NY) Correspondence: Bruce H. Johnsonbaugh; Eckhoff & Hoppe; Suite 3125; 333 Market Street; San Francisco; CA; 94105; US Patent Application Number: 20030199759 Date filed: April 15, 2003 Abstract: A coronary catheter is provided having a series of radiopaque length markers applied to the mid-region of the catheter, wherein the mid-region of the catheter lies directly behind the heart when the catheter is in its deployed position prior to coronary angioplasty. The length markers are applied to the mid-region a known distance apart, allowing the length of a coronary occlusion to be directly measured on an x-ray image of the occlusion by simply comparing the length of the occlusion with the known distance between two or more of the radiopaque markers. Excerpt(s): This application claims the benefit of and priority from U.S. provisional application Serial No. 60/373,593 filed Apr. 18, 2002. This invention pertains generally to coronary catheters. More particularly, the present invention provides radiopaque length markers along the central region of the catheter which extends behind the patient's heart. The radiopaque length markers applied on this portion of the catheter facilitates fairly accurate direct measurement of the length of coronary artery occlusions so that a stent of proper length can be utilized in the affected coronary artery. The problem addressed by the present invention is accurately and quickly determining the length of a coronary artery occlusion during a balloon angioplasty/stenting surgical procedure. Knowing the precise length of the occlusion allows the cardiologist to utilize

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a stent of proper length. Using a stent of improper length may have serious consequences for the patient, or at the very least require removal of the improper stent and a second procedure. The use of a stent which is too short results in restinosis. A stent which is too long may cause rupturing of the artery. At present, the cardiologist examines an x-ray taken during the surgical procedure. Unfortunately, the x-ray has no direct reference measurement points or markers. The cardiologist must estimate the length of stent to be used. The present invention solves this problem by applying radiopaque length markings to the catheter used in the procedure. The present invention thereby allows the cardiologist to quickly make a relatively precise, direct measurement of the occlusion length based on the x-ray. The direct measurement afforded is significantly more accurate than the estimates required by the prior art. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Delivery of microparticle-conjugated drugs for inhibition of stenosis Inventor(s): Iversen, Patrick L.; (Corvallis, OR), Kipshidze, Nicholas; (New York, NY) Correspondence: Perkins Coie Llp; P.O. Box 2168; Menlo Park; CA; 94026; US Patent Application Number: 20030206960 Date filed: July 2, 2002 Abstract: Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, an angioplasty procedure and/or stent implantation. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, an antisense oligonucleotide, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 10/138,589 filed on May 3, 2002, which is incorporated herein in its entirety by reference. The present invention relates to methods of treating or preventing hyperproliferative disease, e.g. stenosis, in blood vessels, and in particular to preventing stenosis following vascular injury, by delivery of a microparticle-conjugated antirestenotic drug, such as rapamycin, to a site of vascular injury. Albiero R et al., "Short- and intermediate-term results of.sup.32P radioactive b-emitting stent implantation in patients with coronary artery disease." Circulation 101:18-26 (2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Device and method for minimizing restenosis after angioplasty treatment Inventor(s): Neuberger, Wolfgang; (F.T. Labuan, MY) Correspondence: Bolesh J. Skutnik; 515 Shaker Road; East Longmeadow; MA; 01028; US Patent Application Number: 20030181894 Date filed: March 21, 2002

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Abstract: A novel device and method for preventing restenosis and streamlining the angioplasty procedure. The device and method provide a fiberoptic guidewire, or, alternatively, a light-conducting catheter, to decrease the size of the angioplasty device, decrease the overall time of the procedure, and increase the safety of the procedure. The present invention delivers radiation to a sclerotized area after balloon angioplasty treatment to prevent restenosis Radiation delivered via the catheter or fiberoptic guidewire discourages the cell proliferation and cell growth after angioplasty, thereby improving the chances of avoiding restenosis. Excerpt(s): This invention relates generally to a method and device using a targeted light source and a photosensitizer to streamline the process of repairing internal body passageways, prevent restenosis, and minimize re-injury after angioplasty treatment. The most common problem with any angioplasty procedure is restenosis, a re-closing of the affected passageway opened by the procedure. This effect is believed to be due to cell proliferation, triggered by the exerted pressure and the lesion caused by the balloon angioplasty. Restenosis occurs in about 30% of patients. The use of stents, or tiny expanding metal scaffolds, is the most common method used to prevent restenosis. However, restenosis through the stent or around the stented area is quite common. Constrictions in the coronary artery are caused by a buildup of plaque. Plaque can occur in many forms, from a thick viscous consistency (similar to toothpaste) to a rock-hard consistency depending on the proportion of components, which may include calcium, fibrous tissue, fatty deposits, organized clots and thrombus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Devices and methods for preventing distal embolization using flow reversal in arteries having collateral blood flow Inventor(s): Barbut, Denise R.; (New York, NY) Correspondence: O'melveny & Meyers; 114 Pacifica, Suite 100; Irvine; CA; 92618; US Patent Application Number: 20030171769 Date filed: March 12, 2003 Abstract: The invention provides a medical device having a catheter and one or more expandable constricting/occluding members. The catheter is adapted for use with therapeutic or diagnostic devices, including an angioplasty/stent catheter and an atherectomy catheter. The constrictor/occluder is mounted at the distal end of the catheter. Manometers may be mounted distal to one or more constrictors for measuring pressure distal to the constrictor(s). Methods of using the devices are disclosed for preventing distal embolization during extracranial or intracranial carotid artery, vertebral artery, or coronary artery procedures, or procedures involving any vessel having collateral flow by reversing flow in the diseased vessel. Excerpt(s): This is a continuation of U.S. application Ser. No. 09/915,648, filed Jul. 25, 2001, incorporated herein by reference in its entirety. The present invention relates generally to devices and methods useful in treating patients with occlusive vascular disease. More specifically, the invention provides devices capable of reversing blood flow in a first artery so that blood flows into a second artery during an invasive procedure, thereby avoiding distal embolization of vascular debris in the first artery. Collateral channels are present in arterial, venous, and lymphatic circulation throughout the body. Collateral circulation is established through connection(s) or anastomoses between two vessels supplying or draining two adjacent vascular regions. Blood supply

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to an organ is maintained through these collateral channels when the main vessel is obstructed. Collateral circulation, therefore, provides a compensatory mechanism that allows amelioration of the detrimental effect of blood flow cessation due to obstruction of a vascular pathway. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Distal protection and delivery system and method Inventor(s): Thielen, Joseph M.; (Buffalo, MN) Correspondence: Joseph M. Thielen; 3027 Cameron AVE. S.E.; Buffalo; MN; 55313; US Patent Application Number: 20030212434 Date filed: June 11, 2003 Abstract: A distal protection and delivery system is used to collect and remove embolic debris in the blood vessel. The system includes a guidewire, a filter assembly, and a distal introducer. The distal introducer can be positioned on a distal end of an introducer catheter or an angioplasty catheter or other interventional catheter. The guidewire has a small ferrule or locking mechanism fixed to it that does not affect the flexibility, torqueability, or trackability in comparison to standard guidewires. The introducer containing the filter assembly is advanced over the guidewire to a site distal to the lesion. Upon retraction of the guidewire proximally, the ferrule latches with an ejector latch of the filter assembly. Either advancement of the guidewire distally or retraction of the distal introducer proximally allows the filter assembly to be ejected from the distal introducer and into the blood vessel. Excerpt(s): The present invention relates to a distal protection and delivery system that is placed using a guidewire in a tubular member of the human body that has a lesion or injury that requires diagnosis or therapy without allowing emboli to be released downstream. More specifically the invention relates to an intravascular system that is placed percutaneously into a blood vessel of the body that has a lesion to be treated by angioplasty, stent placement, atherectomy, thrombectomy, or other therapy, or diagnosis. The blood vessel to be treated can include the coronary, carotid, femoral, popliteal, or other vessel having a vascular lesion that requires interventional treatment. During treatment of such blood vessels, embolic debris can be embolized downstream causing blockage to distal capillary beds and arterioles. This vascular blockage results in reduced tissue perfusion and compromised tissue function. Placement of a distal protection device downstream of the treatment site can allow emboli to be collected and removed from the body rather than causing embolic injury. The distal protection and delivery system of the present invention includes a guidewire that can navigate tortuous blood vessel to reach the vessel lesion as easily as other standard prior art guidewires. The system also includes a filter assembly that is not attached to the guidewire and therefore can be delivered with an introducer to a site distal to the vessel lesion separately from the guidewire. Distal protection devices have been used in tubular vessels of the body including arteries and veins in order to prevent emboli such as thrombi, plaque, and other embolic debris from drifting downstream and causing distal tissue injury. Most distal protection devices have filters that are attached directly to the distal portion of a guidewire or to a portion of a catheter. Filter devices can sometimes be used during surgery, during percutaneous interventional procedures, and also filters can be implanted permanently into the body. The device of the present invention is intended for use during angioplasty or other interventional use. Distal protection devices having a filter attached to a guidewire include the device of Tsugita (U.S. Pat.

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No. 5,910,154), Kerr (U.S. Pat. No. 5,941,896), Ruiz (U.S. Pat. No. 5,928,261), Reger (U.S. Pat. No. 5,160,342), and Ginsburg (U.S. Pat. No. 4,873,978). Tsugita describes a filter apparatus for treating stenosed blood vessels. The guidewire has a filter attached to it for capturing loose embolic material. The filter has an expansion frame having a filter mesh attached to it. One major difficulty with this type of device is that the guidewire cannot traverse a tortuous pathway in a blood vessel with a filter attached and with a holding tube surrounding the filter to hold it in the smaller diameter configuration. The filter along with the holding tube are very stiff and will restrict the ability of the guidewire from making tight turns into small vessels. Kerr describes a conically shaped filter with a porous fabric or a fine fiber mesh. Emboli from an angioplasty procedure are trapped by the filter and connecting loops can be drawn together to hold the emboli. This device shares similar disadvantages to the device of Tsugita. Ruiz describes a removable vascular filter and apparatus that is expanded within the vessel and held in place by a coiled-sheet stent portion with a magnetic band. When the coiled-sheet stent portion is released within the blood vessel, it uncoils to engage a wall of the vessel and deploys the filter element across the flow path. This device would be very stiff due to its configuration and would have much difficulty traversing a tortuous vascular pathway. Reger describes a filter device for use during angioplasty or atherectomy having a filter assembly mounted on a flexible catheter or guidewire. The device contains a filter element such as a polyester cloth that can be closed using a drawstring. A rotating motion can be used to twist the stocking filter to aid in containing the embolic material. This device has a filter permanently attached to the guidewire and will therefore have much greater stiffness than a standard guidewire, thereby limiting its access to smaller vessels and vessels with difficult conformation. Ginsburg describes a catheter device with a filter at the end of a wire that is entered percutaneously from the downstream side of the lesion. This device is extremely limited by virtue of reduced or nonexistent access to the blood vessel in most cases downstream of the lesion. This device also shares the difficulties associated with having a permanently attached filter that will result in a stiff device. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Endothelialization of vascular surfaces Inventor(s): Colb, A. Mark; (West Roxbury, MA), Gold, Herman K.; (Brookline, MA) Correspondence: Kriegsman & Kriegsman; 665 Franklin Street; Framingham; MA; 01702; US Patent Application Number: 20040029268 Date filed: January 29, 2003 Abstract: Endothelialization of vascular surfaces. According to one aspect, the invention involves a technique for re-endothelializing an artery whose endothelial layer has been damaged by balloon angioplasty. The technique comprises, in one embodiment, introducing into the bloodstream of a patient, prior to performing the angioplasty, a quantity of a bispecific antibody, the bispecific antibody having a first antigen binding site directed against a surface marker common to both endothelial progenitor cells (EPCs) and endothelial cells (ECs) and having a second antigen binding site directed against a subendothelial epitope. The bispecific antibody is introduced in a quantity sufficient to bind a substantial percentage of circulating EPCs and circulating ECs. In this manner, once the angioplasty has been performed and the target epitopes on the subendothelium have been exposed, the bispecific antibodies that have already become

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bound to the circulating EPCs and ECs also then bind to the subendothelium. Thus seeded by the bound EPCs and ECs, the exposed subendothelium is covered after a short period of proliferation and differentiation. Excerpt(s): The present application claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Patent Application Serial No. 60/352,684, filed Jan. 29, 2002, in the names of A. Mark Colb and Herman K. Gold, said provisional patent application being incorporated herein by reference. The present application relates generally to the treatment of arterial atherosclerotic disease and relates more particularly to techniques for reducing the occurrence of occlusions following treatment for arterial atherosclerotic disease. Atherosclerosis, which involves the deposition of a fatty plaque on the luminal surface of an artery, is one of the leading causes of death and disability in the world. This is because the deposition of plaque on the luminal surface of an artery causes a narrowing of the cross-sectional area of the artery. Such a narrowing reduces or effectively blocks blood flow distal to the site of the narrowing, causing ischemic damage to those tissues supplied by the artery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Expandable intraluminal graft Inventor(s): Schatz, Richard A.; (Paradise Valley, AZ) Correspondence: Wood, Phillips, Katz, Clark & Mortimer; 500 W. Madison Street; Suite 3800; Chicago; IL; 60661; US Patent Application Number: 20030195617 Date filed: May 30, 2003 Abstract: A plurality of expandable and deformable intraluminal vascular grafts are expanded within a blood vessel by an angioplasty balloon associated with a catheter to dilate and expand the lumen of a blood vessel. The grafts may be thin-walled tubular members having a plurality of slots disposed substantially parallel to the longitudinal axis of the tubular members, and adjacent grafts are flexibly connected by a single connector member disposed substantially parallel to the longitudinal axis of the tubular members. Excerpt(s): The invention relates to an expandable intraluminal graft for use within a body passageway or duct and, more particularly, expandable intraluminal vascular grafts which are particularly useful for repairing blood vessels narrowed or occluded by disease; and a method and apparatus for implanting expandable intraluminal grafts. Intraluminal endovascular grafting has been demonstrated by experimentation to present a possible alternative to conventional vascular surgery. Intraluminal endovascular grafting involves the percutaneous insertion into a blood vessel of a tubular prosthetic graft and its delivery via a catheter to the desired location within the vascular system. Advantages of this method over conventional vascular surgery include obviating the need for: surgically exposing, incising, removing, replacing, or bypassing the defective blood vessel. Structures which have previously been used as intraluminal vascular grafts have included coiled stainless steel springs; helically wound coil springs manufactured from an expandable heat-sensitive material; and expanding stainless steel stents formed of stainless steel wire in a zig-zag pattern. In general, the foregoing structures have one major disadvantage in common. Insofar as these structures must be delivered to the desired location within a given body passageway in a collapsed state, in order to pass through the body passageway, there is no effective control over the final,

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expanded configuration of each structure. For example, the expansion of a particular coiled spring-type graft is predetermined by the spring constant and modulus of elasticity of the particular material utilized to manufacture the coiled spring structure. These same factors predetermine the amount of expansion of collapsed stents formed of stainless steel wire in a zig-zag pattern. In the case of intraluminal grafts, or prostheses, formed of a heat sensitive material which expands upon heating, the amount of expansion is likewise predetermined by the heat expansion characteristics of the particular alloy utilized in the manufacture of the intraluminal graft. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Filter flush system and methods of use Inventor(s): Tsugita, Ross S.; (Mountain View, CA) Correspondence: Glenn M. Seager; Crompton, Seager & Tufte, Llc; Suite 800; 1221 Nicollet Avenue; Minneapolis; MN; 55403-2420; US Patent Application Number: 20040006370 Date filed: July 17, 2003 Abstract: A filter flush system for temporary placement of a filter in an artery or vein is disclosed. The system typically includes a guidewire insertable within a guiding catheter, which has an occlusion balloon disposed about its distal end. The guidewire has an expandable filter, which can be collapsed to pass through a lumen and distal port of the guiding catheter. The lumen is adapted to receive a variety of endovascular devices, including angioplasty, atherectomy, and stenting catheters. Fluid medium or blood can be infused through the lumen of the guiding catheter to flush embolic material or mobile plaque generated during the endovascular procedures toward the expanded filter deployed downstream from the region of interest. Methods of using the filter flush system to entrap and remove embolic material from the vessel are also disclosed. Excerpt(s): The present invention relates generally to devices and methods useful in capturing embolic material in blood vessels. More specifically, the devices and methods provide a vessel filtering system for temporary deployment in arteries such as the carotid arteries and the aorta, and veins such as the subclavian vein and the superior vena cava. The system also includes a guidewire for directing endovascular devices, e.g., atherectomy, stent-deployment, or angioplasty catheters, to a region of interest and a guiding catheter with fluid flushing capability to assist in filtering. Treatment of thrombotic or atherosclerotic lesions in blood vessels using the endovascular approach has recently been proven to be an effective and reliable alternative to surgical intervention in selected patients. For example, directional atherectomy and percutaneous translumenal coronary angioplasty (PTCA) with or without stent deployment are useful in treating patients with coronary occlusion. Atherectomy physically removes plaque by cutting, pulverizing, or shaving in atherosclerotic arteries using a catheter-deliverable endarterectomy device. Angioplasty enlarges the lumenal diameter of a stenotic vessel by exerting mechanical force on the vascular walls. In addition to using the angioplasty, stenting, and/or atherectomy on the coronary vasculature, these endovascular techniques have also proven useful in treating other vascular lesions in, for example, carotid artery stenosis, peripheral arterial occlusive disease (especially the aorta, the iliac artery, and the femoral artery), renal artery stenosis caused by atherosclerosis or fibromuscular disease, superior vena cava syndrome, occlusion iliac vein thrombosis resistant to thrombolysis. It is well recognized

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that one of the complications associated with endovascular techniques is the dislodgment of embolic materials generated during manipulation of the vessel, thereby causing occlusion of the narrower vessels downstream and ischemia or infarct of the organ which the vessel supplies. In 1995, Waksman et al. disclosed that distal embolization is common after directional atherectomy in coronary arteries and saphenous vein grafts. See Waksman et al., American Heart Journal 129(3): 430-5 (1995), incorporated herein by reference. This study found that distal embolization occurs in 28% (31 out of 111) of the patients undergoing atherectomy. In January 1999, Jordan, Jr. et al. disclosed that treatment of carotid stenosis using percutaneous angioplasty with stenting procedure is associated with more than eight times the rate of microemboli seen using carotid endarterectomy. See Jordan, Jr. et al. Cardiovascular surgery 7(1): 33-8 (1999), incorporated herein by reference. Microemboli, as detected by transcranial Doppler monitoring in this study, have been shown to be a potential cause of stroke. The embolic materials include calcium, intimal debris, atheromatous plaque, thrombi, and/or air. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Growth arrest homeobox gene Inventor(s): Gorski, David H.; (Cleveland, OH), Walsh, Kenneth; (Concord, MA) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20030199067 Date filed: August 27, 2001 Abstract: A novel growth arrest homeobox gene has been discovered and the nucleotide sequences have been determined in both the rat and the human. The expression of the novel homeobox gene inhibits vascular smooth muscle cell growth. The growth arrest homeobox gene hereinafter referred to as the "Gax gene" and its corresponding proteins are useful in the study of vascular smooth muscle cell proliferation and in the treatment of blood vessel diseases that result from excessive smooth muscle cell proliferation, particularly after balloon angioplasty. Excerpt(s): The leading cause of death in the United States and in most developed countries, is atherosclerosis. Atherosclerosis is a disease affecting the large and medium size muscular arteries such as the coronary or carotid arteries and the large elastic arteries such as the aorta, iliac, and femoral arteries. This disease causes narrowing and calcification of arteries. The narrowing results from deposits of substances in the blood in combination with proliferating vascular smooth muscle cells. The deposits known as atherosclerotic plagues are comprised of lipoproteins, mainly cholesterol, proliferating vascular smooth muscle cells and fibrous tissue, and extra cellular matrix components, which are secreted by vascular smooth muscle cells. As the plagues grow, they narrow the lumen of the vessel decreasing arterial blood flow and weakening the effected arteries. The resulting complications potentially include a complete blockage of the lumen of the artery, with ischemia and necrosis of the organ supplied by the artery, ulceration and thrombus formation with associated embolism, calcification, and aneurysmal dilation. When atherosclerosis causes occlusion of the coronary arteries, it leads to myocardial disfunction, ischemia and infarction and often death. Indeed, 2025% of deaths in the United States are attributable to atherosclerotic heart disease. Atherosclerosis also leads to lower extremity gangrene, strokes, mesenteric occlusion, ischemic encephalopathy, and renal failure, depending on the specific vasculature

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involved. Approximately 50% of all deaths in the United States can be attributed to atherosclerosis and its complications. Present treatments for atherosclerosis include drugs and surgery, including ballon angioplasty. As a result of angioplasty, vascular smooth muscle cells de-differentiate and proliferate and leading to leading to reocclusion of the vessel. These de-differentiated vascular smooth muscle cells deposit collagen and other matrix substances, that contribute to the narrowing of vessel. Vascular cells secrete growth factors such as platelet derived growth factor, which induces both chemotaxis and proliferation of vascular smooth muscle cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Heteroaryl nitriles Inventor(s): Gabriel, Tobias; (San Francisco, CA), Krauss, Nancy Elisabeth; (Mountain View, CA), Mirzadegan, Taraneh; (Los Altos, CA), Palmer, Wylie Solang; (Mountain View, CA), Smith, David Bernard; (San Mateo, CA) Correspondence: Roche Palo Alto Llc; 3431 Hillview Avenue; Patent DEPT., M/s A2250; Palo Alto; CA; 94304; US Patent Application Number: 20030212097 Date filed: December 3, 2002 Abstract: The present invention relates to compound of formula (I) 1wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and n are as defined in the description and claims and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof. The compounds are useful for the treatment of diseases which are associated with cysteine proteases such as osteoporosis, osteoarthritis, rheumatoid arthritis, tumor metastasis, glomerulonephritis, atherosclerosis, myocardial infarction, angina pectoris, instable angina pectoris, stroke, plaque rupture, transient ischemic attacks, amaurosis fugax, peripheral arterial occlusive disease, restenosis after angioplasty and stent placement, abdominal aortic aneurysm formation, inflammation, autoimmune disease, malaria, ocular fundus tissue cytopathy and respiratory disease. Excerpt(s): This application claims the priority benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Application Serial No. 60/336,750, filed Dec. 4, 2001, the disclosure of which is herein incorporated by reference. Cysteine proteases have been viewed as lysosomal mediators of terminal protein degradation. Several newly discovered members of this enzyme class, however, are regulated proteases with limited tissue expression, which implies specific roles in cellular physiology and thus would allow a specific targeting of these activities without interfering with the general lysosomal protein degragation. Development of inhibitors of specific cysteine proteases promises to provide new drugs for modifying immunity, osteoporosis, neurodegeneration, chronic inflammation, cancer and malaria (Bromme, Drug News Perspect 1999, 12(2), 73-82; Chapman et al., Annu. Rev. Phys. 1997, 59, 63-88). Cysteine proteases can be grouped into two superfamilies: the family of enzymes related to interleukin 1.beta. converting enzyme (ICE), and the papain superfamily of cysteine proteases. Presently there are at least 12 human proteases of the papain family from which sequences have been obtained (cathepsin B, L, H, S, O, K, C, W, F, V(L2), Z(X) and bleomycin hydrolase). Cathepsin K was first discovered as a cDNA prominent in rabbit osteoclasts and referred to as OC-2 (Tezuka et al., J. Biol. Chem. 1994, 269, 1106-1109). Recent observations indicate that cathepsin K is the most potent mammalian elastase yet described. Cathepsin K, as well as cathepsins S and L, are also potent collagenases and gelatinases. Macrophages appear capable of mobilizing the active proteases within

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endosomal and/or lysosomal compartments to the cell surface under special circumstances. In this case, the cell surface/substrate interface becomes a compartment from which endogenous inhibitors are excluded and can be viewed as a physiological extension of the lysosome. This type of physiology is an innate trait of osteoclasts, a bone macrophage, and may also be exploited by other macrophages or cells in the context of inflammation. The abundance of cathepsin K in osteoclasts leads to the suggestion that cathepsin K plays an important role in bone resorption. Studies revealed that cathepsin K is the predominant cysteine protease in osteoclasts and is specifically expressed in human osteoclasts. A correlation between inhibition of cysteine protease activity and bone resorption has been reported (Lerner et al., J. Bone Min. Res. 1992, 7, 433; Everts et al., J. Cell. Physiol. 1992, 150, 221). Cathepsin K has been detected in synovial fibroblasts of RA patients, as well as in mouse hypertrophic chondrocytes (Hummel et al., J. Rheumatol. 1998, 25(10), 1887-1894.). Both results indicate a direct role of cathepsin K in cartilage erosion. P. Libby (Libby et al., J. Clin. Invest. 1998, 102 (3), 576-583) reported that normal arteries contain little or no cathepsin K or S whereas macrophages in atheroma contained abundant immunoreactive cathepsins K and S. Most of the elastolytic activity of tissue extracts associated with human atheroma compared to non-atherosclerotic arteries could be inhibited with E64, a non-selective cysteine protease inhibitor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Inflatable member having elastic expansion with limited range Inventor(s): Bagaoisan, Celso Jacinto; (Newark, CA), Muni, Ketan P.; (San Jose, CA), Powers, Gerard F.; (San Ramon, CA) Correspondence: Fulwider Patton Lee & Utecht, Llp; Howard Hughes Center; 6060 Center Drive; Tenth Floor; Los Angeles; CA; 90045; US Patent Application Number: 20030229307 Date filed: March 25, 2003 Abstract: An intravascular catheter such as an angioplasty catheter having a catheter shaft with an expandable tubular element on its distal end which upon inflation to an internal pressure at or above a threshold pressure expands in a manner which is related to the internal pressure. The maximum transverse dimension of the expandable tubular element is generally not greater than the maximum transverse dimension of the catheter shaft. Preferably, the expandable tubular element is formed of a heat shrinkable polymeric material such as a polyolefinic ionomer. Excerpt(s): This application is a continuation-in-part application based on copending application Ser. No. 07/758,630 filed Sep. 12, 1991, and entitled FORMED IN PLACE BALLOON FOR VASCULAR CATHETER. This invention generally relates to intravascular catheters, such as balloon dilatation catheters used in percutaneous transluminal coronary angioplasty (PTCA). PTCA is a widely used procedure for the treatment of coronary heart disease. In this procedure, a balloon dilatation catheter is advanced into the patient's coronary artery and the balloon on the catheter is inflated within the stenotic region of the patient's artery to open up the arterial passageway and thereby increase the blood flow therethrough. To facilitate the advancement of the dilatation catheter into the patient's coronary artery, a guiding catheter having a preshaped distal tip is first percutaneously introduced into the cardiovascular system of a patient by the Seldinger technique through the brachial or femoral arteries. The catheter is advanced until the preshaped distal tip of the guiding catheter is disposed

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within the aorta adjacent the ostium of the desired coronary artery. The guiding catheter is twisted or torqued from the proximal end, which extends out of the patient, to guide the distal tip of the guiding catheter into the ostium. A balloon dilatation catheter may then be advanced through the guiding catheter into the patient's coronary artery until the balloon on the catheter is disposed within the stenotic region of the patient's artery. The balloon is inflated to open up the arterial passageway and increase the blood flow through the artery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Irradiation conversion of thermoplastic to thermoset polymers Inventor(s): Zamore, Alan M.; (Monsey, NY) Correspondence: Alan M Zamore; 23 Mountain Ave; Monsey; NY; 10952; US Patent Application Number: 20040002729 Date filed: June 30, 2003 Abstract: Disclosed is a radiation-crosslinkable thermoplastic polymer composition, a process for the preparation thereof, an angioplasty balloon and a medical catheter made using such a composition. The composition contains a reactive monomer cross-linker facilitates cross-linking of the reaction product upon contact of the cross-linkercontaining composition with energy from a radiation source. Excerpt(s): This application is a Continuation-In-Part of co-pending U.S. application Ser. No. 08/947,000 filed Oct. 8, 1997 which is a Continuation-In-Part of U.S. application Ser. No. 08/727,145, filed on Oct. 8, 1996, now U.S. Pat. No. 5,900,444 issued May 4, 1999. This invention relates generally to the conversion of thermoplastic polymers into thermoset polymers and more specifically to such thermoset polymers exhibiting improved physical and chemical properties, relative to the corresponding thermoplastic polymers. Illustrative of such polymers are the polyurethane thermoplastic polymers, the co-polyester elastomer thermoplastic polymers, and the nylon elastomer thermoplastic polymers all of which can be advantageously converted to thermoset forms in the presence of a reactive monomer crosslinker and actinic radiation. Thermoplastic polymers, are relatively easy to process into a wide variety of fabricated products. Unfortunately, however, for many of these thermoplastic polymers, the high temperature stability, and their physical properties such as mechanical strength at elevated temperatures, as well as their stability in some commonly-used organic solvents, are less than might be desired. Accordingly, methodology has been previously developed to provide heat-induced crosslinking to convert certain thermoplastic polymers, such as thermoplastic polyurethanes, into thermoset polyurethanes having the desired stability at high temperatures and in the presence of solvents. By way of illustration, U.S. Pat. No. 4,255,552 discloses thermoset polyurethane elastomers obtained by adding organic peroxides to a liquid polyurethane-forming composition prior to reacting the composition to form the polyurethane. The '552 patent teaches that a liquid polyurethane-forming composition containing "unactivated hydrogen peroxide" may be formed in a mold into a desired article and then heated to solidify and thermoset the article, or a composition in solid form such as sheet, crumbs, or granules containing "unactivated hydrogen peroxide" may be provided which are can then be formed into a desired article that is then thermoset by heating the article in a press. The organic peroxides disclosed in the '552 patent are said to have a half-life of greater than one hour at 100 deg C. Unfortunately, these peroxide-containing compositions are less stable than might be desired or necessary for a thermoplastic process such as extrusion or molding.

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The peroxide containing polyurethane composition would most likely thermoset prior to forming the desired finished article, thus providing technology that is not commercially practical for thermoplastics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Low profile metal/polymer tubes Inventor(s): Wang, Lixiao; (Long Lake, MN) Correspondence: Glenn M. Seager; Crompton, Seager & Tufte, Llc; Suite 800; 1221 Nicollet Avenue; Minneapolis; MN; 55403-2420; US Patent Application Number: 20030199851 Date filed: May 30, 2003 Abstract: The present invention relates generally to elongate support members, preferably for use with a catheter for performing medical procedures including percutaneous transluminal coronary angioplasty. An elongate support member, comprising a proximal end, a distal end, is disclosed. The proximal end of the elongate support member, is formed to define a plurality of flanges. A linkage connects the flanges, and a lumen within the shaft defined by connecting the flanges. The elongate support member comprises an improved catheter shaft design that maintains pushability, flexibility, and torquability while limiting the kinking. Excerpt(s): The present invention relates generally to catheters for performing medical procedures including percutaneous transluminal coronary angioplasty. More particularly, the present invention relates to balloon catheters with an improved proximal shaft design. The use of intravascular catheters has become an effective method for treating many types of vascular disease. In general, an intravascular catheter is inserted into the vascular system of the patient and navigated through the vasculature to a desired target site. Using this method, virtually any target site in the patient's vascular system may be accessed, including the coronary, cerebral, and peripheral vasculature. Examples of therapeutic purposes for intravascular catheters include percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA). Intravascular catheters are commonly used in conjunction with a guidewire. A guidewire may be advanced through the patient's vasculature until it has reached a target location. Once in place, a catheter may be threaded onto the guidewire and urged distally until the distal end of the catheter reaches a target location. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for treating a desired area in the vascular system of a patient Inventor(s): Crocker, Ian R.; (Stone Mtn., GA), Hillstead, Richard A.; (Duluth, GA), Larsen, Charles E.; (Cumming, GA), Meloul, Raphael F.; (Atlanta, GA), Rosen, Jonathan J.; (Alpharetta, GA), Waksman, Ron; (Atlanta, GA), Weldon, Thomas D.; (Gainesville, GA) Correspondence: Mark J. Murphy; Cook, Alex, Mcfarron, Manzo,; Cummings & Mehler, LTD.; 200 West Adams ST., STE. 2850; Chicago; IL; 60606; US Patent Application Number: 20030229259 Date filed: April 11, 2003

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Abstract: Apparatus and method are described for delivery of a treating element, such as a radiation source, through a catheter to a desired site in the vascular system of a patient, such as a coronary artery, for inhibiting the formation of scar tissue such as may occur in restenosis following balloon angioplasty. The apparatus includes an elongated flexible catheter tube having proximal and distal end portions, with a lumen extending therebetween, and a diameter sufficiently small for insertion in to a patient's vascular system. One or more treating elements, such as a capsule or pellet containing radioactive material, is positionable within the lumen and movable between the proximal and distal end portions under the force of liquid flowing through the lumen. A method for using such apparatus, including a method for using such apparatus simultaneously with a balloon angioplasty procedure, is disclosed. Excerpt(s): The present invention relates generally to the delivery of treating elements by a catheter to a selected site within the vascular system of a patient. More particularly, the present invention relates to method and apparatus for the delivery of a treating element, such as a radiation source, through a catheter to a desired site, such as a coronary artery, for inhibiting wound healing response, such as restenosis following balloon angioplasty. It is known that the human body's healing response to wounds typically includes the formation of what is commonly called scar tissue. This response also occurs within the vascular system of a person following injury to a blood vessel. An injury that provokes the formation of scar tissue may occur in various locations within the vascular system, such as in the carotid artery or in coronary bypasses, or in various ways, such as trauma from surgical or diagnostic procedures. One area of the vascular system of particular concern with respect to such injuries is coronary arteries that are subjected to procedures for removing or reducing blockages due to plaque within the arteries. Partial and even complete blockage of coronary arteries by the formation of an atherosclerotic plaque is a well known and frequent medical problem. Such blockages may be treated using atherectomy devices, which mechanically remove the plaque; hot or cold lasers, which vaporize the plaque; stents, which hold the artery open; and other devices and procedures which have the objective of allowing increased blood flow through the artery. The most common such procedure is the percutaneous transluminal coronary angioplasty (PTCA) procedures--more commonly referred to as balloon angioplasty. In this procedure, a catheter having an inflatable balloon at its distal end is introduced into the coronary artery, the uninflated balloon is positioned at the stenotic site and the balloon is inflated. Inflation of the balloon disrupts and flattens the plaque against the arterial wall, and stretches the arterial wall, resulting in enlargement of the intraluminal passageway and increased blood flow. After such expansion, the balloon is deflated and the balloon catheter removed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for delivering radiation to an intraluminal site in the body Inventor(s): Tam, Lisa A.; (Lake Forest, CA), Trauthen, Brett A.; (Newport Beach, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030208096 Date filed: August 31, 2001 Abstract: Disclosed is a thin film radiation source, which may be used to deliver a radioactive dose to a site in a body lumen. The source comprises a thin flexible substrate, and a layer of radioisotope attached thereto. The source may further comprise

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additional layers such as one or more tie layers disposed between the substrate and the radioisotope layer and one or more outer coating layers. In one embodiment, the source is wrapped around an inflatable balloon. Inflation of the balloon at a treatment site positions the source directly adjacent to the vessel wall, and allows irradiation of the site following or simultaneously with a balloon angioplasty, stent implantation, or stent sizing procedure. Excerpt(s): This application is a continuation-in-part of Ser. No. 09/025,921, filed Feb. 19, 1998. This invention relates to radiation sources which may be transported on catheters and used to deliver radiation to prevent or slow restenosis of an artery traumatized such as by percutaneous transluminal angioplasty (PTA). PTA treatment of the coronary arteries, percutaneous transluminal coronary angioplasty (PTCA), also known as balloon angioplasty, is the predominant treatment for coronary vessel stenosis. Approximately 300,000 procedures were performed in the United States in 1990 and nearly one million procedures worldwide in 1997. The U.S. market constitutes roughly half of the total market for this procedure. The increasing popularity of the PTCA procedure is attributable to its relatively high success rate, and its minimal invasiveness compared with coronary by-pass surgery. Patients treated by PTCA, however, suffer from a high incidence of restenosis, with about 35% or more of all patients requiring repeat PTCA procedures or by-pass surgery, with attendant high cost and added patient risk. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of inhibiting restenosis Inventor(s): Sahota, Harvinder; (Seal Beach, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040018113 Date filed: July 26, 2002 Abstract: A method of inhibiting restenosis is disclosed. The method includes reducing contaminants during manufacturing of angioplasty devices and during angioplasty procedures. An angioplasty device is preferably examined for contaminants prior to the angioplasty procedure, and the contaminants are reduce if present. Excerpt(s): The present invention relates to medical procedures and, in particular a method for inhibiting restenosis through improved manufacturing techniques for angioplasty catheters, and improved procedure techniques. The cause of restenosis in angioplasty has been a mystery to health care professionals. Many diseases cause body lumens to undergo stenosis or a narrowing of a canal within the body. The resulting reduced blood flow can permanently damage tissue and organs. Stenotic regions that limit or obstruct coronary blood flow are the major cause of ischemic heart disease related mortality and result in 500,000-600,000 deaths in the United States annually. The therapeutic alternatives available for treatment of stenosis include intervention (alone or in combination of therapeutic agents) to remove the blockage, replacement of the blocked segment with a new segment of artery, or the use of catheter-mounted devices such as a balloon catheter to dilate the artery. The dilation of an artery with a balloon catheter is called percutaneous transluminal angioplasty (PTA). During angioplasty, a balloon catheter in a deflated state is inserted within a stenotic segment of a blood vessel

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and is inflated and deflated a number of times to expand the vessel. A stent may also be delivered, as know in the art. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for flow augmentation in patients with occlusive cerebrovascular disease Inventor(s): Barbut, Denise; (New York, NY) Correspondence: O'melveny & Meyers; 114 Pacifica, Suite 100; Irvine; CA; 92618; US Patent Application Number: 20030199802 Date filed: May 6, 2003 Abstract: The invention provides a method for augmenting circulation in a patient having carotid stenosis. An elongate tubular member is provided having a lumen communicating with a port at a distal end. The tubular member is inserted into a peripheral artery and the distal port is advanced into a first carotid artery substantially free of a lesion where the patient possesses a second carotid artery substantially occluded by a lesion. Blood is perfused into the first carotid artery through the tubular member. Contralateral flow is augmented to improve perfusion to an ischemic region distal to the carotid stenosis. Angioplasty and stenting can be used to open the lesion in the second carotid artery. Excerpt(s): This is a divisional application of co-pending application Ser. No. 09/483,370, filed Apr. 25, 2000, now U.S. Pat. No. 6,558,356, which is a divisional application of co-pending application Ser. No. 09/232,438, filed Jan. 15, 1999, now U.S. Pat. No. 6,161,547, all of which are incorporated herein by reference in their entirety. The present invention generally relates to medical devices useful in treating patients with acute stroke or occlusive cerebrovascular disease. More specifically, the invention provides an extra/intracranial device capable of removing blood from a peripheral artery or symptomatic carotid artery and returning the blood to the contralateral carotid artery, thereby providing a means of augmenting the collateral vasculature and maintaining perfusion distal to the offending lesion. The device may employ neuroprotective agents, hypothermic perfusion, and an atherectomy device or an extracorporeal pumping mechanism to remove a vascular occlusion and reestablish cerebral perfusion. Stroke is the third most common cause of death in the United States and the most disabling neurologic disorder. Approximately 700,000 patients suffer from stroke annually. Stroke is a syndrome characterized by the acute onset of a neurological deficit that persists for at least 24 hours, reflecting focal involvement of the central nervous system, and is the result of a disturbance of the cerebral circulation. Outcome following stroke is influenced by a number of factors, the most important being the nature and severity of the resulting neurologic deficit. The patient's age, the cause of stroke, and coexisting medical illness also affect prognosis. Overall, less than 80% of patients with stroke survive for at least 1 month, and approximately 35% have been cited for the 10-year survival rates. Of patients who survive the acute period, up to 75% regain independent function, while approximately 15% require institutional care. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for treating vascular disease by inhibiting myeloid differentiation factor 88 Inventor(s): Arditi, Moshe; (Encino, CA), Rajavashisth, Tripathi; (El Camino Village, CA), Shah, Prediman K.; (Los Angeles, CA) Correspondence: Richard H. Zaitlen, ESQ.; Pillsbury Winthrop Llp; Intellectual Property Group; 725 South Figueroa Street, Suite 2800; Los Angeles; CA; 90017-5406; US Patent Application Number: 20030148986 Date filed: December 12, 2002 Abstract: Methods included herein describe the treatment of atherosclerosis and other vascular diseases such as thrombosis, restenosis after angioplasty and/or stenting, and vein-graft disease after bypass surgery, by inhibition of the expression or biologic activity of myeloid differentiation factor 88 (MyD88). Also included is an intravascular device coated with a compound that inhibits MyD88; thereby imparting an improved efficacy to the device. TLR-4 cell signal transduction is at least partially responsible for the manifestation, continuation, and/or worsening of atherosclerosis and other forms of vascular disease. The present invention provides several means with which to inhibit this signal transduction pathway by affecting the biological activity of MyD88. Excerpt(s): This is a Continuation-in-Part of U.S. patent application Ser. No. 10/128,166, filed Apr. 23, 2002, which is incorporated herein in its entirety. This application also claims the benefit of priority under 35 U.S.C.sctn. 119 of provisional application 60/341,359, filed Dec. 17, 2001, the contents of which are hereby incorporated by reference. This invention relates to methods for inhibiting the biological activity of myeloid differentiation factor 88 ("MyD88"), and, in particular, to methods for treating vascular disease by inhibiting the expression or signaling by MyD88. Heart disease remains the leading cause of death worldwide, accounting for nearly 30% of the annual total (i.e., approximately 15 million people). Heart and vascular disease debilitate many more individuals every year. For many, atherosclerotic disease is a life-long process; it may possess an initial stage in childhood, without clinical manifestation until middle age or later. Its development has been repeatedly linked to unhealthy lifestyles (e.g., tobacco use, unbalanced diet, and physical inactivity). Much progress has been made in the detection and treatment of various forms of heart and vascular disease, but preventative measures and assorted treatment regimens are usually incapable of halting or curing the underlying disease condition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Microcatheter Inventor(s): Blackledge, Victor R.; (Cologne, MN), Glantz, Jerald; (Lake Elmo, MN), Lee, Nathan T.; (Golden Valley, MN), Vreeman, Daniel J.; (Rogers, MN) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030225434 Date filed: May 30, 2002 Abstract: The present disclosure relates to a catheter having an elongate body defining a lumen. An angioplasty balloon is mounted adjacent a distal end of the elongate body. A flexible tip is located proximal to the angioplasty balloon. In one embodiment, the flexible tip is integral with the elongate body.

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Excerpt(s): This invention pertains to a catheter device. More particularly, this invention pertains to microcatheters adapted to navigate within narrow vessels such as cerebral vessels. Strokes are the leading cause of disability among adults in the United States, and are the third leading cause of death. A stroke occurs when blood flow to one or more regions of the brain is interrupted causing brain cells to die. The extent of damage is dependent upon the part of the brain affected. Common symptoms of a stroke include loss of mental capacity, changes in vision or speech, loss of muscle control and coordination, dizziness, loss of sensation and weakness. A stroke is most commonly caused by atherosclerosis. Atherosclerosis is the accumulation of plaque (i.e., fatty deposits) within blood vessels. A stroke occurs when plaque accumulates within a cerebral vessel to the extent that blood flow is substantially blocked. Blood clots that form in the brain, or emboli that become lodged in vessels of the brain, can also block blood flow to portions of the brain thereby causing a stroke. Occasionally, a stroke is caused by bleeding within the brain (e.g., rupture of a cerebral aneurysm). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Mutant plasminogen activator-inhibitor type 1 (PAI-1) and uses thereof Inventor(s): Lawrence, Daniel A.; (Derwood, MD), Stefansson, Steingrimor P.; (Gaithersburg, MD) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030216321 Date filed: September 30, 2002 Abstract: Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notatably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells. Such conditions include atherosclerosis, post angioplasty restenosis, fibrosis associated with chronic inflammation or chemotherapy, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. Also disclosed are peptides of such mutant proteins, mutant-specific antibodies, nucleic acid molecules, particularly DNA, encoding the mutant protein and host cells transformed by such nucleic acids. Excerpt(s): The invention in the field of biochemistry and medicine relates to compositions comprising mutant proteins of plasminogen activator inhibitor-type 1 (PAI-1) which have the capacity to inhibit the enzyme elastase and to inhibit vitronectin (Vn)-dependent migration of cells. This invention also relates to uses of these proteins for the treatment of diseases and disorders associated with elastase activity or in which migration and migration-driven proliferation of cells have pathophysiologic consequences. Plasminogen activators (PAs) are specific serine proteinases that activate the proenzyme plasminogen, by cleavage of a single Arg-Val peptide bond, to the enzyme plasmin (Saksela O, Biochim Biophys Acta (1985) 823:35-65). Two plasminogen

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activators are found in mammals, tissue-type PA (tPA) and urokinase-type PA (uPA) (Saksela O et al, Annu Rev Cell Biol (1988) 4:93-126). These enzymes are thought to influence critically many biological processes, including vascular fibrinolysis (Bachmann E, Thromb Haemost (1987) 10:227-265), ovulation (Hsuch A J W et al, In: Haseltine F P et al, eds, Meiotic Inhibition: Molecular Control of Meiosis New York: Liss 1988:227-258), inflammation (Pollanen J et al., Adv Cancer Res (1991) 57:273-328), tumor metastasis (Dano K et al., Adv Cancer Res (1985) 44:139-266), angiogenesis (Moscatelli D et al., Biochim Biophys Acta (1988) 948:67-85), and tissue remodeling (Saksela, supra). The regulation of PAs is a complex process controlled on many levels. The synthesis and release of PAs are governed by various hormones, growth factors, and cytokines (Saksela, supra; Dano et al., supra). Following secretion, PA activity can be regulated both positively and negatively by a number of specific protein-protein interactions. Activity can be enhanced or concentrated by interactions with fibrin (Hoylaerts M et al., J Biol Chem (1982) 257:2912-2919), the uPA receptor (uPAR) (Ellis V et al., Semin Thromb Hemost (1991) 17:194-200), the tPA receptor (tPAR) (Hajjar K A et al., J Biol Chem (1990) 265:2908-2916), or the plasminogen receptor (Plow E F et al., Thromb Haemost (1991) 66:32-36). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Propanoic acid derivatives as intergrin receptor antagonists Inventor(s): Bandiera, Tiziano; (Gambolo, IT), Cozzi, Paolo; (Milano, IT), Galvani, Arturo; (Parabiago, IT), Vianello, Paola; (Milano, IT) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030144311 Date filed: November 1, 2002 Abstract: Novel propanoic acid derivatives are integrin receptor antagonists or inhibitors, in particular of the avb3 integrin receptor. The compounds of the invention are for instance useful for the treatment of solid tumors by inhibition of angiogenic growth of tumor vessel network, thus promoting tumor regression, inhibition of metastatic spread, thus avoiding cancer metastases, inhibition of bone resorption, thus controlling osteoporosis, inhibition of smooth muscle cells migration into neointima, thus blocking restenosis after percutaneous coronary angioplasty and the treatment of other pathological conditions mediated by cell adhesion, cell migration or angiogenesis such e.g. diabetic retinopaty, rheumatoid arthritis and inflammation. Excerpt(s): The present invention relates to novel non-peptide compounds which bind to the integrin receptor.alpha.v.beta.3, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents. Integrins are membrane-bound receptors that mediate cell-matrix and cell-cell adhesion interactions. The compounds of present invention are useful for the treatment of diseases in which the pathology arises from ligation of an integrin receptor, especially the vitronectin receptor, and therefore of diseases mediated by cell adhesion and angiogenesis. The compounds of present invention are useful in selectively inhibiting or antagonizing.alpha.v.beta.3 integrin and therefore are useful for the treatment of solid tumors by inhibition of angiogenic growth of tumor vessel network, thus promoting tumor regression, inhibition of metastatic spread, thus avoiding cancer metastases, inhibition of bone resorption, thus controlling osteoporosis, inhibition of smooth muscle

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cells migration into neointima, thus blocking restenosis after percutaneous coronary angioplasty and the treatment of other pathological conditions mediated by cell adhesion, cell migration or angiogenesis such e.g. diabetic retinopaty, rheumatoid arthritis and inflammation. The utility of antagonists of the.alpha.v.beta.3 integrin and related cell surface adhesive protein receptors is well known in the art. and the pharmaceutically acceptable salts thereof. The present invention includes within its scope all possible isomers, stereoisomers and optical isomers and their mixtures, and the metabolites and the metabolic precursors or bioprecursors of the compounds of formula (I). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Reducing torque needed to perform a cardiovascular procedure Inventor(s): Day, Ronald W.; (Salt Lake City, UT) Correspondence: Kirton & Mcconkie; Suite 1800; 60 East South Temple; Salt Lake City; UT; 84111; US Patent Application Number: 20040015152 Date filed: May 20, 2003 Abstract: Systems and methods for providing a medical device for use in right coronary arteriography or right coronary angioplasty and stent placement, wherein the medial device and use thereof reduces the amount of torque required to perform the cardiovascular procedure. A catheter is provided that is U-shaped and includes an angle near the distal end. The catheter is used to perform a selective right coronary arteriography procedure at or near the orifice of a blood vessel with a limited amount of torque and catheter manipulation. The safety and efficacy of the right coronary arteriography procedure using the limited-torque technique and catheter results in a decreased incidence of intimal injury due to a reduction in the amount of torque required to finalize proper placement of the catheter. Excerpt(s): This application claims priority to U.S. Provisional Patent Application Serial No. 60/381,982 filed May 20, 2002, entitled DESIGN OF A CATHETER FOR RIGHT CORONARY ARTERIOGRAPHY AND A GUIDING CATHETER FOR RIGHT CORONARY ANGIOPLASTY AND STENT PLACEMENT AND LIMITED TORQUE METHODS OF USE. The present invention relates to reducing torque needed to perform a cardiovascular procedure. In particular, the present invention relates to systems and methods for providing a medical device for use in right coronary arteriography or right coronary angioplasty and stent placement, wherein the medial device and use thereof reduces the amount of torque required to perform the cardiovascular procedure. A variety of medical procedures are currently performed on the cardiovascular system of a patient. For example, selective coronary arteriography, which is an X-ray examination of the blood vessels or chambers of the heart, is occasionally indicated in patients with congenital or acquired heart disease. In the procedure, a catheter is inserted into a blood vessel of the patient's groin or arm. The tip of the catheter is positioned either in the heart or at the beginning of the arteries supplying the heart. A contrast medium is injected through the catheter that is visible by X-ray. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Reinforced monorail balloon catheter Inventor(s): Duane, Patrick J.E.; (Galway, IE), Fitzmaurice, Thomas K.; (Galway, IE), Gilson, Paul; (Galway, IE) Correspondence: Medtronic Ave, INC.; 3576 Unocal Place; Santa Rosa; CA; 95403; US Patent Application Number: 20030176837 Date filed: March 19, 2003 Abstract: The invention is a dilation catheter which comprises an elongated catheter shaft, a guide wire tube, and an angioplasty balloon. The distal end of the balloon is attached to the distal portion of the guide wire tube, and the proximal portion of the balloon is attached to the distal portion of the catheter shaft. A stiffening wire is attached to the inner wall of the catheter shaft at a plurality of points along its length. The distal extremity of the guide wire tube is decreased in size relative to the proximal portion of the guide wire tube. A fluid is contained within the guide wire lumen. Excerpt(s): This invention relates to a dilatation catheter and more particularly to a dilatation catheter construction of particular utility as a monorail dilatation catheter. Monorail dilatation catheters are becoming increasingly popular in angioplasty procedures because, unlike over-the-wire catheters that require guide wire extenders to perform a catheter exchange, the monorail dilatation catheter construction enables one monorail dilatation catheter to be exchanged readily for another. U.S. Pat. No. 4,762,129 to Bonzel discloses one such catheter having a guide wire lumen only at the distal segment of the catheter, for coupling the catheter and the guide wire together. The guide wire tube extends through the balloon, from the distal end of the catheter to a point proximal to the balloon. Rapid exchange and manipulation of the dilatation catheter is facilitated because the catheter segment in contact with the surface of the guide wire is only as long as the balloon. Although conventional monorail-type catheters allow rapid catheter exchange, they tend to lack stiffness along their shaft length proximal to the exchange joint, at which point, the catheter gains the benefit of the guide wire to impart stiffness to the catheter. This lack of stiffness along the proximal portion of the catheter makes it difficult to advance the catheter through the body passageway. Bonzel addresses this problem, in part, by providing an integral stabilizing means that extends from the catheter's proximal end, through the inflation lumen, to the distal end of the balloon. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stent for angioplasty and associated production process Inventor(s): Curcio, Maria; (Saluggia, IT), Rolando, Giovanni; (Chivasso, IT), Vallana, Franco; (Torino, IT) Correspondence: Terry L. Wiles, ESQ.; Popovich & Wiles,pa; Ids Center; 80 South 8th Street, Suite 1902; Minneapolis; MN; 55402; US Patent Application Number: 20030195613 Date filed: May 7, 2003 Abstract: A stent has surface sculpturing, preferably on its outer surface only, having, for example, microspheres, having the function of increasing the actual geometric surface area of the stent, of creating undercuts and roughness to encourage the

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application of coatings of active or activatable agents, as well as of improving the attachment of the stent to the blood vessel wall. Excerpt(s): This application is a continuation of application Ser. No. 08/997,597, filed Dec. 23, 1997, the contents of which are hereby incorporated herein by reference. The present invention concerns a stent for angioplasty and an associated method of production thereof. The term "stent for angioplasty" is intended to indicate generally devices intended for endoluminal application (for example, within a blood vessel) in association with the technique of percutaneous transluminal coronary angioplasty, or PTCA, usually effected by catheterisation of a stenotic site. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Substituted imidazoles as selective modulators of bradykinin B2 receptors Inventor(s): DeSimone, Robert; (Durham, CT), He, Xiao-Shu; (Branford, CT), Hodgetts, Kevin; (Killingworth, CT), Hutchison, Alan; (Madison, CT), Maynard, George D.; (Clinton, CT), Rachwal, Stanislaw; (Middletown, CT), Shaw, Kenneth; (Weston, CT) Correspondence: Leslie-anne Horvath; Patent Department; Neurogen Corporation; 35 NE Industrial RD.; Branford; CT; 06405; US Patent Application Number: 20030229076 Date filed: September 16, 2002 Abstract: Disclosed are compounds of the formula: 1or the pharmaceutically acceptable non-toxic salts thereof wherein Y, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.7' are variables defined herein, which compounds are modulators of Bradykinin B.sub.2 receptors. These compounds are therefore useful in the diagnosis and treatment of renal diseases, heart failure, hypertension, Meniere's disease, vaginal inflammation and pain, peripheral circulatory disorders, climacteric disturbance, retinochoroidal circulatory disorders, myocardial ischemia, myocardial infarction, postmyocardial infarction syndrome, angina pectoris, restenosis after percutaneous transluminal coronary angioplasty, hepatitis, liver cirrhosis, pancreatitis, ileus, diabetes, diabetic complications, male infertility, glaucoma, pain, asthma, and rhinitis, and for the increase of permeability of the blood-brain barrier or the blood-brain-tumor barrier. Excerpt(s): This application claims priority from U.S. provisional patent application No. 60/176,869, filed Jan. 18, 2000. This invention relates to certain imidazoles which, when appropriately substituted, are selective modulators of Bradykinin B.sub.2 receptors (BK2 receptors). This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of central and peripheral disorders. Additionally, compounds of this invention are useful as positive controls in assays for BK-2 receptor activity and when appropriately labeled as probes for the localization of BK-2 receptors in tissue sections. Bradykinin (BK), a nonapeptide, and the closely related decapeptide kallidin (Lys-BK), are produced by proteolytic cleavage of high molecular weight kininogen by plasma kallikreins. The effects of bradykinin and kallidin are mediated by specific seven transmembrane Gprotein coupled receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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System and device for minimizing embolic risk during an interventional procedure Inventor(s): Muller, Paul F.; (San Carlos, CA), Patel, Udayan G.; (San Jose, CA), Stack, Richard S.; (Chapel Hill, NC) Correspondence: Fulwider Patton Lee & Utecht, Llp; Howard Hughes Center; 6060 Center Drive; Tenth Floor; Los Angeles; CA; 90045; US Patent Application Number: 20030195556 Date filed: May 29, 2003 Abstract: A device for trapping plaque against the vascular wall includes a tubularshaped net which is made from a blood-permeable and biocompatable material having expandable members attached to each end of the tubular net. The expandable members are placed in their expanded position within a blood vessel to maintain the tubular net against the area of plaque to be treated with an interventional procedure. A balloon angioplasty procedure or stenting procedure is subsequently performed within the inner lumen formed in the tubular net. The tubular net prevents any emboli which may be created during the interventional procedure from entering into the bloodstream. Excerpt(s): This application is a continuation of application Ser. No. 09/560,209 filed Apr. 28, 2000, which is assigned to the same Assignee as the present application. The present invention relates to angioplasty procedures, and more particularly, to a system and device for preventing arterial plaque from dislodging from the arterial wall during procedures such as, for example, percutaneous transluminal coronary angioplasty (PTCA) or percutaneous transluminal angioplasty (PTA), especially carotid PTA, and entering into the bloodstream where the embolic debris can occlude the flow of oxygenated blood to vital organs, such as the brain, which can cause devastating consequences to the patient. The present invention also relates to methods for using such a system and device. In typical carotid PTA procedures, a guiding catheter or sheath is percutaneously introduced into the cardiovascular system of a patient through the femoral arteries and advanced through the vasculature until the distal end of the guiding catheter is in the common carotid artery. A guidewire and a dilatation catheter having a balloon on the distal end are introduced through the guiding catheter with the guidewire sliding within the dilatation catheter. The guidewire is first advanced out of the guiding catheter into the patient's carotid vasculature and is directed across the arterial lesion. The dilatation catheter is subsequently advanced over the previously advanced guidewire until the dilatation balloon is properly positioned across the arterial lesion. Once in position across the lesion, the expandable balloon is inflated to a predetermined size with a radiopaque liquid at relatively high pressure to radially compress the atherosclerotic plaque of the lesion against the inside of the artery wall and thereby dilate the lumen of the artery. The balloon is then deflated to a small profile so that the dilatation catheter can be withdrawn from the patient's vasculature and the blood flow resumed through the dilated artery. As should be appreciated by those skilled in the art, while the above-described procedure is typical, it is not the only method used in angioplasty. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of post-angioplasty restenosis and atherosclerosis with Ras antagonists Inventor(s): George, Jakob; (Tel Aviv-Yafo, IL), Keren, Gad; (Kiryat Ono, IL), Kloog, Yoel; (Herzlia, IL) Correspondence: Lerner, David, Littenberg,; Krumholz & Mentlik; 600 South Avenue West; Westfield; NJ; 07090; US Patent Application Number: 20030203942 Date filed: April 22, 2003 Abstract: Disclosed are methods for inhibiting Ras activity such as cell proliferation associated with vascular injury such as post-angioplasty restenosis and atherosclerosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof. Excerpt(s): This application is a continuation of U.S. application Ser. No. 10/023,545, filed Dec. 18, 2001, which is a continuation-in-part of U.S. application Ser. No. 09/597,332, filed Jun. 19, 2000, which claims priority under 35 U.S.C.sctn. 119(e) from U.S. Application No. 60/140,192, filed Jun. 18, 1999. The contents of these two applications are hereby incorporated herein by reference in their entireties. The present invention relates to the inhibition of the onset of or the treatment of non-malignant diseases, and particularly diseases having pathologies involving Ras-induced proliferation of cells. Autoimmune diseases include disorders involving dysfunction of the immune system, which mediates tissue damage. Any organ may be affected by such processes through precipitation of immune complexes, cellular immunity, or inappropriate generation or action of immuno-hormones such as cytokines. Epidemiologically, autoimmune diseases are significant because of the numbers of patients that they affect and the serious morbidity and mortality that they cause. Common chronic systemic diseases in this group include diabetes mellitus, thyroid disease, rheumatoid arthritis, systemic lupus erythmatosus (SLE), primary antiphospholipid syndrome (APS), and a variety of diseases that affect the central nervous system. Neurological autoimmune diseases include disorders specific to the nervous system such as myasthenia gravis, Lambert Eaton myasthenic syndrome, Guillain-Barre syndrome, polymyositis, and multiple sclerosis. In addition, there are neurological complications of the systemic autoimmune diseases. Factors predisposing to autoimmune diseases include genetic predisposition and environmental agents such as certain infections and pharmaceutical products. Such factors result in pathological activation of the immune response in susceptible individuals, which is generally controlled by T lymphocytes (T cells). The activation of T cells and B subtypes, involves a complex interaction of cell surface receptors resulting in equally complex signal transduction pathways which eventually affect gene regulation. Full activation of lymphocytes requires parallel stimulation of several signal transduction pathways. See Ohtsuka et al., Biochim. Biophys. Acta. 1310:223-232 (1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of inhibitors of soluble epoxide hydrolase to inhibit vascular smooth muscle cell proliferation Inventor(s): Hammock, Bruce D.; (Davis, CA), Weiss, Robert H.; (Vacaville, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030139469 Date filed: January 23, 2002 Abstract: The present invention provides methods of slowing or inhibiting vascular smooth muscle (VSM) cell proliferation to slow the development or recurrence of atherosclerosis by contacting VSM cells with soluble epoxide hydrolase (sEH) inhibitors. Further, the methods of the invention can be used to slow or to inhibit vascular restenosis after angioplasty and the stenosis of vascular stents. Further, the methods of the invention can be used to slow or to inhibit the stenosis of hemodialysis grafts and other natural and synthetic vascular grafts. Excerpt(s): This invention relates to slowing or inhibiting the proliferation of vascular smooth muscle cells and the consequent slowing or inhibiting of the development of atherosclerosis. Eicosanoids serve both paracrine and autocrine functions in a variety of cells, including those of the vasculature. The cis-epoxyeicosatrienoic acids (EETs), epoxides of arachidonic acid comprising one class of eicosanoid, consist of four regioisomers which are synthesized from arachidonic acid in a reaction catalyzed by the cytochrome P-450 system (Capdevila et al., FASEB J., 6:731-736 (1992)). These compounds are synthesized by endothelial cells and are rapidly taken up by arterial vascular smooth muscle (VSM) cells (Fang et al., Prostaglandins Leukot. Essent. Fatty Acids, 57:367-371 (1997); Fang et al., Circ. Res., 79:784-793 (1996); Rosolowsky et al., Biochim. Biophys. Acta, 1299:267-277 (1996)). Epoxide hydrolases are enzymes which, broadly defined, convert epoxides to diols by the addition of water (Fretland et al., Chem. Biol. Interact. 2000Dec. 1; 129(1-2):41.-59., 129:41-59 (2000)). While these enzymes have been studied largely in light of their roles in degrading and de-toxifying mutagenic xenobiotics, at least the soluble epoxide hydrolase also is critical in the control of EET levels, due to its ability to catalyze the degradation of the EETs into diols (Chacos et al., Arch. Biochem. Biophys., 223:639-648 (1983)). Pharmacological attenuation of sEH activity causes a secondary increase in EET levels (Yu et al., Circ. Res. 2000. Nov. 24.; 87(11):992.-8, 87:992-998 (2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of propionyl L-carnitine for the preparation of a medicament capable of inducing apoptosis Inventor(s): Calvani, Menotti; (Rome, IT), Pisano, Claudio; (Aprilia (LT) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030220363 Date filed: February 3, 2003 Excerpt(s): The present invention relates to the use of propionyl L-carnitine and the pharmaceutically acceptable salts thereof for the preparation of medicaments useful in the treatment of pathologies whose treatment gains a benefit from inducement of

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apoptosis, in particular blood vessels, such as restenosis after angioplasty or coronary stenting, or in particular tumours. A number of studies demonstrated that cell proliferation plays a pivotal role in atherosclerosis, hypertension pathogenesis and restenosis after angioplasty or coronary stenting (Ross, 1976; Schwartz, 1990). Many experimental studies, carried out on human atherosclerotic plaques, demonstrated that cell proliferation is a determining phenomenon both in the early phases and in the progression of the plaque. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vascular catheter with expanded distal tip for receiving a thromboembolic protection device and method of use Inventor(s): Wholey, Mark H.; (Oakmont, PA), Wholey, Michael H.; (San Antonio, TX), Wholey, Petra; (San Antonio, TX) Correspondence: Timothy D. Broms; Pietragallo, Bosick & Gordon; One Oxford Centre, 38th Floor; 301 Grant Street; Pittsburgh; PA; 15219; US Patent Application Number: 20030176886 Date filed: January 21, 2003 Abstract: A vascular catheter including a radially expandable segment, such as an inflatable balloon, and an expanded distal tip having an increased storage volume is disclosed. The inflatable balloon segment of the catheter may be used to provide traditional balloon angioplasty to a portion of a blood vessel narrowed by stenosis, and the expanded distal tip of the catheter apparatus may be used to safely capture, store, and remove a thromboembolic protection device such as an embolic filter used to catch pieces of plaque and other embolic material dislodged during the balloon angioplasty procedure. The catheter of the present invention provides an effective means for dilating a narrowed portion of a blood vessel, as well as preventing the need for deploying a second catheter system to capture and retrieve the embolic filter. The present invention also greatly reduces the chance for plaque and other thromboembolic material to escape from the embolic filter and enter the patient's bloodstream. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/363,310 filed Mar. 12, 2002. The present invention relates to transluminal angioplasty, and more particularly relates to a vascular catheter for providing balloon angioplasty while at the same time providing improved thromboembolic protection. Methods of utilizing the catheter apparatus to provide balloon angioplasty and thromboembolic protection are also provided. It is common practice today to open occluded (i.e. blocked) or stenotic (i.e. narrowed) blood vessels by inserting a guide wire and then a catheter carrying a balloon shaped segment and inflating the balloon, which exerts a radial force to press stenosis outward against the wall of the blood vessel. This procedure is called balloon angioplasty. Frequently, an implantable metallic stent will also be used to provide greater radial strength at the stenotic portion of the blood vessel, and to provide longer-term patency. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with angioplasty, 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 “angioplasty” (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 angioplasty. You can also use this procedure to view pending patent applications concerning angioplasty. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON ANGIOPLASTY Overview This chapter provides bibliographic book references relating to angioplasty. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on angioplasty include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “angioplasty” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on angioplasty: •

Diabetic Foot: Medical and Surgical Management Source: Totowa, NJ: The Humana Press, Inc. 2002. 475 p. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail: [email protected] PRICE: $135.00, plus shipping and handling. ISBN: 0896039250. Summary: Fifteen percent of people with diabetes mellitus (nearly 2 million people) will develop foot ulcerations in their lifetime. The consequences of these problems are not only important to the individual patient and their families, but to every health care system in the world. Diabetic foot ulcerations and infections are the main cause for hospitalization of the patient with diabetes, thus placing a substantial financial burden on society. This textbook focuses on the medical and surgical management of foot problems in people with diabetes. The text offers 22 chapters, covering topics including the principles of care in the surgical patient with diabetes; epidemiology and the health

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care costs of diabetic foot problems; the physiology and pathophysiology of wound healing; diabetic polyneuropathy (nerve disease); microvascular changes in the diabetic foot; the clinical features and diagnosis of macrovascular disease; foot pressure abnormalities in the diabetic foots; the biomechanics of the diabetic foot; clinical examination of the diabetic foot and identification of the at-risk patient; radiographic changes of the diabetic foot; microbiology and treatment of diabetic foot infections; Charcot changes in the diabetic foot; principles of treatment of the chronic wound; local care of the diabetic foot; surgical treatment of the ulcerated foot; amputations and rehabilitation; reconstruction of soft tissue defects of the foot; the role of growth factors in the treatment of diabetic foot ulceration; living skin equivalents for diabetic foot ulcers; vascular surgery for the diabetic foot; angioplasty and other noninvasive surgical procedures; and footwear in the prevention of diabetic foot problems. The text includes a section of full-color plates, numerous black and white photographs, and a detailed subject index. Each chapter concludes with a list of references. •

Coronary artery disease in women: What all physicians need to know Source: Philadelphia, PA: American College of Physicians: American Society of Internal Medicine. 1999. 615 pp. Contact: Available from American College of Physicians-American Society of Internal Medicine, 190 North Independence Mall West, Philadelphia, PA 19106. Telephone: (215) 351-2400 or (800) 523-1546 / fax: (215) 351- 2799 / e-mail: [email protected] / Web site: http://www.acponline.org. $43 for nonmembers, $32 for members; plus shipping and handling. Summary: This book for health care practitioners reviews all important aspects of coronary artery disease, with an emphasis on gender differences, age, and race. It contains five parts: the introduction, prevention, diagnosis, management, and conclusion. The section on prevention discusses smoking; diabetes and insulin resistance; the history and pharmacologic management of lipids/cholesterol; nutrition; hypertension; obesity; exercise as prevention; aspirin, antioxidants, and alcohol; and issues in hormone replacement therapy. The diagnosis section provides information on the differential diagnosis of chest pain, noninvasive testing techniques, and influence of gender in coronary angiography. Topics in the the section on management include angina pectoris, acute coronary syndromes, bypass grafting risks, angioplasty, congestive heart failure, psychosocial issues, and pharmacologic secondary prevention. The concluding section discusses future trends in treatment and research. Each chapter contains a summary and list of references. Numerous charts and graphs present statistical information. The book concludes with an index.

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

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21st Century Complete Medical Guide to Heart Disease, Heart Attack, Cholesterol, Coronary Artery Disease, Bypass Surgery, Angioplasty ¿ Authoritative Federal Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 1931828342; http://www.amazon.com/exec/obidos/ASIN/1931828342/icongroupinterna

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Abrupt Closure During Coronary Angioplasty by Jean Marco (Editor); ISBN: 2287003614; http://www.amazon.com/exec/obidos/ASIN/2287003614/icongroupinterna

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Access to and Availability of Coronary Artery Bypass Grafting and Coronary Angioplasty by Terence English; ISBN: 0113215975; http://www.amazon.com/exec/obidos/ASIN/0113215975/icongroupinterna

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Advances in Coronary Angioplasty: Drug Eluting Stents [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3MZ; http://www.amazon.com/exec/obidos/ASIN/B00008R3MZ/icongroupinterna

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Angioplasty by G. David Jang; ISBN: 0070323526; http://www.amazon.com/exec/obidos/ASIN/0070323526/icongroupinterna

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Angioplasty and Atherectomy: Intravascular Intervention by Lasers, Balloons, Atherotomes and Stents by Geoffrey N. White; ISBN: 0070697221; http://www.amazon.com/exec/obidos/ASIN/0070697221/icongroupinterna

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Angioplasty and Stentiong of Carotid by Michel Henry (Editor), et al; ISBN: 1841842621; http://www.amazon.com/exec/obidos/ASIN/1841842621/icongroupinterna

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Angioplasty in peripheral artery disease by Delma E. Cowley; ISBN: 0644247797; http://www.amazon.com/exec/obidos/ASIN/0644247797/icongroupinterna

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Angioplasty: For Narrowed Heart Kidney or Leg Arteries by Julia Ann Purcell; ISBN: 0939838222; http://www.amazon.com/exec/obidos/ASIN/0939838222/icongroupinterna

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Atlas of Coronary Balloon Angioplasty (Fundamental and Clinical Cardiology, Vol 23) by Bernhard Meier, Vivek K. Mehan; ISBN: 0824794079; http://www.amazon.com/exec/obidos/ASIN/0824794079/icongroupinterna

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Balloon Catheter Coronary Angioplasty by Paolo Angelini, Denton A. Cooley; ISBN: 0879933070; http://www.amazon.com/exec/obidos/ASIN/0879933070/icongroupinterna

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Basic Coronary Balloon Angioplasty by Bowes, Cumberland; ISBN: 0340571918; http://www.amazon.com/exec/obidos/ASIN/0340571918/icongroupinterna

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Clinical Coronary Angioplasty: A Text and Atlas by Jeffrey A. Brinker; ISBN: 0815112343; http://www.amazon.com/exec/obidos/ASIN/0815112343/icongroupinterna

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Complications of Coronary Angioplasty by Alexander J.R. Black, et al; ISBN: 0824784405; http://www.amazon.com/exec/obidos/ASIN/0824784405/icongroupinterna

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Coronary and Peripheral Angiography and Angioplasty; ISBN: 0713145080; http://www.amazon.com/exec/obidos/ASIN/0713145080/icongroupinterna

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Coronary Angioplasty by Bernhard Meier; ISBN: 0808918923; http://www.amazon.com/exec/obidos/ASIN/0808918923/icongroupinterna

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Coronary Angioplasty; ISBN: 9998471990; http://www.amazon.com/exec/obidos/ASIN/9998471990/icongroupinterna

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Coronary Angioplasty by David A. Clark; ISBN: 047156110X; http://www.amazon.com/exec/obidos/ASIN/047156110X/icongroupinterna

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Coronary Angioplasty (Cardiovascular Clinics, Vol 19, No 2) by Sheldon Goldberg (Editor); ISBN: 0803641621; http://www.amazon.com/exec/obidos/ASIN/0803641621/icongroupinterna

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Coronary Angioplasty CME Booklet (Paper Only) by DA Clark; ISBN: 0471588385; http://www.amazon.com/exec/obidos/ASIN/0471588385/icongroupinterna

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Coronary Angioplasty Tutorial by David A. Clark Clark (Editor); ISBN: 0471561096; http://www.amazon.com/exec/obidos/ASIN/0471561096/icongroupinterna

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Coronary Angioplasty: A Controlled Model for Ischemia (Developments in Cardiovascular Medicine, 58) by G.T. Meester (Editor), Patrick W. Serruys (Editor); ISBN: 0898388198; http://www.amazon.com/exec/obidos/ASIN/0898388198/icongroupinterna

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Coronary Arteriography and Angioplasty by John S. Douglas, Spencer B., III King; ISBN: 007034616X; http://www.amazon.com/exec/obidos/ASIN/007034616X/icongroupinterna

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Coronary Artery Bypass Graft Surgery and Percutaneous Transluminal Coronary Angioplasty: Ratings of Appropriateness and Necessity by a Canadian Pane by C. David Naylor; ISBN: 0833014528; http://www.amazon.com/exec/obidos/ASIN/0833014528/icongroupinterna

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Coronary Balloon Angioplasty (Series in Interventional Cardiology) by Ronald E. Vlietstra (Editor), David R., Jr. Holmes (Editor); ISBN: 0865422958; http://www.amazon.com/exec/obidos/ASIN/0865422958/icongroupinterna

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Coronary Laser Angioplasty (Series in Interventional Cardiology) by Frank Litvack (Editor); ISBN: 0865421897; http://www.amazon.com/exec/obidos/ASIN/0865421897/icongroupinterna

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Coronary Laser Angioplasty: An Update by K. R. Karsch (Editor), K. K. Haase (Editor); ISBN: 3798508828; http://www.amazon.com/exec/obidos/ASIN/3798508828/icongroupinterna

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Current Status of Carotid Bifurcation Angioplasty and Stenting by Frank J. Veith (Editor), Max Amor (Editor); ISBN: 0824704959; http://www.amazon.com/exec/obidos/ASIN/0824704959/icongroupinterna

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Effect of Calcium Channel Blockers on the Incidence of Restenosis After Coronary Balloon Angioplasty & on the Progression of Coronary Artery Disease by Joseph Dens; ISBN: 9058672980; http://www.amazon.com/exec/obidos/ASIN/9058672980/icongroupinterna

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Endovascular Skills: Guidewires, Catheters, Arteriography, Balloon Angioplasty & Stents; ISBN: 1576261409; http://www.amazon.com/exec/obidos/ASIN/1576261409/icongroupinterna

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Endovascular Skills: Guidewires, Catheters, Arteriography, Balloon Angioplasty, Stents by Peter A. Schneider; ISBN: 1576260798; http://www.amazon.com/exec/obidos/ASIN/1576260798/icongroupinterna

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Guide to Coronary Angioplasty and Stenting Ination of Immune Status and by Peter J. Hubner, Peter J.b. Hubner; ISBN: 9057022788; http://www.amazon.com/exec/obidos/ASIN/9057022788/icongroupinterna

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Improvement of Myocardial Perfusion: Thrombolysis, Angioplasty, Bypass Surgery (Developments in Cardiovascular Medicine) by Jurgen Meyer, et al; ISBN: 0898387485; http://www.amazon.com/exec/obidos/ASIN/0898387485/icongroupinterna

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Laser Angioplasty by Timothy A. Sanborn (Editor); ISBN: 0471509922; http://www.amazon.com/exec/obidos/ASIN/0471509922/icongroupinterna

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Laser Disobstruction and Laser-Assisted Balloon Angioplasty by Teruo Matsumoto, et al; ISBN: 0912791667; http://www.amazon.com/exec/obidos/ASIN/0912791667/icongroupinterna

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Lasers in Cardiovascular Disease: Clinical Applications, Alternative Angioplasty Devices, and Guidance Systems by Rodney A. White, Warren S. Grundfest (Editor); ISBN: 0815192592; http://www.amazon.com/exec/obidos/ASIN/0815192592/icongroupinterna

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Noncoronary Angioplasty and Interventional Radiologic Treatment of Vascular Malformations by Laszlo Szlavy, Juan M. Taveras; ISBN: 0812116402; http://www.amazon.com/exec/obidos/ASIN/0812116402/icongroupinterna

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Passing on Bypass Using External CounterPulsation : An FDA Cleared Alternative to Treat Heart Disease Without Surgery, Drugs or Angioplasty. SECOND EDITION by George J. Juetersonke; ISBN: 096781281X; http://www.amazon.com/exec/obidos/ASIN/096781281X/icongroupinterna

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Passing on Bypass Using External Counterpulsation : an FDA Cleared Alternative, to Treat Heart Disease Without Surgery, Drugs or Angioplasty! by George J. Juetersonke, George J. Juetersonke; ISBN: 0967812801; http://www.amazon.com/exec/obidos/ASIN/0967812801/icongroupinterna

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Percutaneous transluminal angioplasty : the Dotter procedure : a manual for the radiologist by G. J. van Andel; ISBN: 0444152296; http://www.amazon.com/exec/obidos/ASIN/0444152296/icongroupinterna

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Percutaneous Transluminal Angioplasty: Technique, Early and Late Results by C. T. Dotter; ISBN: 0387126546; http://www.amazon.com/exec/obidos/ASIN/0387126546/icongroupinterna

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Percutaneous Transluminal Coronary Angioplasty: A Clinical Follow-up Study by F. Stammen; ISBN: 9061865921; http://www.amazon.com/exec/obidos/ASIN/9061865921/icongroupinterna

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Percutaneous Transluminal Coronary Angioplasty: A Review of the Literature Regarding Efficacy and Risks (Rand Report, 4050/1-Cw) by Lee H. Hilborne (Editor), et al; ISBN: 0833011766; http://www.amazon.com/exec/obidos/ASIN/0833011766/icongroupinterna

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Practical Angioplasty by D. Faxon (Editor); ISBN: 0781700841; http://www.amazon.com/exec/obidos/ASIN/0781700841/icongroupinterna

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Practice of Coronary Angioplasty by T. Ischinger (Editor); ISBN: 0387159495; http://www.amazon.com/exec/obidos/ASIN/0387159495/icongroupinterna

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Practice of Coronary Angioplasty; ISBN: 3540159495; http://www.amazon.com/exec/obidos/ASIN/3540159495/icongroupinterna

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Primary Angioplasty in Acute Myocardial Infarction by James E., MD Tcheng (Editor); ISBN: 0896039048; http://www.amazon.com/exec/obidos/ASIN/0896039048/icongroupinterna

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Primer on Laser Angioplasty; ISBN: 0879933291; http://www.amazon.com/exec/obidos/ASIN/0879933291/icongroupinterna

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Ptca: Percutaneous Transluminal Coronary Angioplasty by Ronald E. Vlietstra; ISBN: 0803689624; http://www.amazon.com/exec/obidos/ASIN/0803689624/icongroupinterna

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Restenosis After Percutaneous Transluminal Coronary Angioplasty: Detection, Assessment and Modes of Prevention by W. Desmet; ISBN: 906186626X; http://www.amazon.com/exec/obidos/ASIN/906186626X/icongroupinterna

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Second German Symposium on Laser Angioplasty (Proceedings of S P I E, Vol 1462) by Gerhard J. Muller, H.P. Berlien (Editor); ISBN: 3609630507; http://www.amazon.com/exec/obidos/ASIN/3609630507/icongroupinterna

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So You're Having a Heart Cath and Angioplasty by Magnus Ohman (Author), et al; ISBN: 0470833432; http://www.amazon.com/exec/obidos/ASIN/0470833432/icongroupinterna

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So You're Having Angioplasty: What Happens Next by Stephen, Md. Fort; ISBN: 0968898246; http://www.amazon.com/exec/obidos/ASIN/0968898246/icongroupinterna

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Transluminal Angioplasty by Wilfrido R. Castaneda-Zuniga (Editor); ISBN: 0865770573; http://www.amazon.com/exec/obidos/ASIN/0865770573/icongroupinterna

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Transluminal Angioplasty by Amir Motarjeme; ISBN: 0815159846; http://www.amazon.com/exec/obidos/ASIN/0815159846/icongroupinterna

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Transluminal Coronary: Angioplasty and Intracoronary Thrombolysis by M. Kaltenbach (Editor); ISBN: 0387112197; http://www.amazon.com/exec/obidos/ASIN/0387112197/icongroupinterna

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Ultrasound Angioplasty (Developments in Cardiovascular Medicine, 178) by Robert J. Siegel (Editor); ISBN: 0792337220; http://www.amazon.com/exec/obidos/ASIN/0792337220/icongroupinterna

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

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Has Transluminal Angioplasty Proved to be Efficacious in Treatment of Atherosclerotic Renal Artery Stenosis? Source: in Andreucci, V.E. International Yearbook of Nephrology 1990. Hingham, MA: Kluwer Academic Publishers. 1990. p. 107-119. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA02018-0358. (617) 871-6600. Summary: Percutaneous transluminal angioplasty (PTA) has rapidly advanced to become one of the most popular methods for treating hypertension secondary to renal artery stenosis. This chapter focuses on: the development of PTA; the choice among PTA, surgery, or drug therapy; indications and contraindications for PTA; the effects of PTA on blood pressure, cure rate, and kidney function; the rate of restenosis; and complications which have been observed in using PTA. The use of PTA for preservation of kidney function also is discussed. The discussions with use of tabular and graphical data. 48 references.

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CHAPTER 8. PERIODICALS AND NEWS ON ANGIOPLASTY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover angioplasty.

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

Nicorandil a better adjunct to angioplasty than isosorbide dinitrate for AMI Source: Reuters Industry Breifing Date: February 13, 2004

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Cerebral artery angioplasty reduces recurrent stroke risk Source: Reuters Medical News Date: February 06, 2004

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Angioplasty for MI particularly helpful in women Source: Reuters Medical News Date: January 29, 2004

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Angioplasty for heart attack particularly helpful for women Source: Reuters Health eLine Date: January 29, 2004

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Aggressive diabetes control improves angioplasty outcomes Source: Reuters Medical News Date: January 12, 2004

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Rise in plasma marker after angioplasty linked to cardiac events in CAD patients Source: Reuters Medical News Date: November 21, 2003

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Bypass surgery more cost effective than coronary angioplasty Source: Reuters Medical News Date: October 14, 2003

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Delay weakens angioplasty benefits for heart attack Source: Reuters Health eLine Date: October 07, 2003

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Angioplasty benefits may fade with treatment delays Source: Reuters Medical News Date: October 07, 2003

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Bypass surgery better than angioplasty and stenting in relieving angina Source: Reuters Medical News Date: September 15, 2003

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Heparin coating may protect against stent thrombosis after angioplasty Source: Reuters Medical News Date: September 05, 2003

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Angioplasty outcomes influenced by C-reactive protein levels Source: Reuters Medical News Date: September 05, 2003

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Blockade of specific potassium channels might curb restenosis after angioplasty Source: Reuters Industry Breifing Date: September 04, 2003

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Adding GIK infusion to angioplasty reduces MI mortality Source: Reuters Medical News Date: September 02, 2003

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Diabetics' response to angioplasty influenced by haptoglobin genotype Source: Reuters Medical News Date: August 29, 2003

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Waiting for angioplasty better than immediate fibrinolysis for acute MI patients Source: Reuters Medical News Date: August 20, 2003

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Angioplasty for heart attack worth waiting for Source: Reuters Health eLine Date: August 20, 2003

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•

Angioplasty during off-hours associated with poor outcome Source: Reuters Medical News Date: June 20, 2003

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Angioplasty plus stenting better than thrombolysis for elderly patients with AMI Source: Reuters Medical News Date: June 05, 2003

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Outcomes worse for diabetics after primary angioplasty for acute MI Source: Reuters Medical News Date: May 29, 2003

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Gene therapy may boost success of angioplasty Source: Reuters Health eLine Date: May 22, 2003

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Angioplasty, coronary bypass surgery tied to similar quality of life outcomes Source: Reuters Medical News Date: May 21, 2003

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VEGF gene therapy during angioplasty and stenting can improve myocardial blood flow Source: Reuters Industry Breifing Date: May 19, 2003

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Pretreatment with beta-blockers may improve outcomes of angioplasty for AMI Source: Reuters Industry Breifing Date: March 28, 2003

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Ventricular assistance device may prevent complications during angioplasty Source: Reuters Medical News Date: March 20, 2003

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Intracranial angioplasty may be safer on awake patient Source: Reuters Medical News Date: February 14, 2003

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Benefit of primary angioplasty over thrombolysis maintained for 6 months Source: Reuters Industry Breifing Date: January 31, 2003

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Low level CO suppresses arterial lesions after experimental angioplasty, grafting Source: Reuters Medical News Date: January 21, 2003

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Dangerous gas may improve angioplasty results Source: Reuters Health eLine Date: January 20, 2003

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CORRECTION: Women and men benefit equally from angioplasty Source: Reuters Medical News Date: January 06, 2003

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Photodynamic therapy can prevent femoral artery restenosis after angioplasty Source: Reuters Medical News Date: January 03, 2003

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Angioplasty better than clot busters for treatment of ST-segment elevation AMI Source: Reuters Industry Breifing Date: January 03, 2003

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Women, men benefit equally from angioplasty Source: Reuters Health eLine Date: December 17, 2002

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Study backs longer post-angioplasty therapy Source: Reuters Health eLine Date: November 18, 2002

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Monteplase followed by angioplasty: a potentially "powerful" strategy for AMI Source: Reuters Industry Breifing Date: November 08, 2002

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Fewer emergency bypass surgeries needed for failed angioplasty Source: Reuters Medical News Date: October 15, 2002

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Angioplasty complication fell ten-fold since 1992 Source: Reuters Health eLine Date: October 14, 2002

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Preinfarction angina speeds ST-segment resolution after angioplasty for MI Source: Reuters Medical News Date: October 11, 2002

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Abciximab beneficial when given before primary angioplasty for MI Source: Reuters Industry Breifing Date: October 10, 2002 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “angioplasty” (or synonyms) into the search box, and click on “Search News.” As this service is technology

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

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “angioplasty” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on angioplasty: •

Vascular Access Procedures for American Indian Dialysis Patients Source: IHS Primary Care Provider. 25(10): 153-158. October 2000. Contact: Available from Indian Health Service Clinical Support Center. Two Renaissance Square, Suite 780, 40 North Central Avenue, Phoenix, AZ 85004. (602) 3647777. Fax (602) 364-7788. E-mail: [email protected]. Website: www.ihs.gov. Summary: More than 300,000 patients are currently receiving treatment for chronic renal failure with chronic dialysis in the United States. Access complications are the leading cause for hospitalizations in this population. This article examines renal (kidney) failure and the complications of dialysis access in two groups of patients from two southwestern Native American tribes. As in the general population, comorbid conditions (illnesses in addition to the kidney disease) were common. In the group from Tribe A, 84 percent had diabetes and 97 percent had hypertension (high blood pressure). In the Tribe B group, 66 percent had diabetes and 80 percent had hypertension. Renal failure associated with diabetes mellitus and hypertension is largely preventable by maintaining strict control of serum glucose and blood pressure. There are three general treatment options for end stage renal disease (ESRD): no therapy (which results in death), peritoneal dialysis, and hemodialysis. In this article, the authors review results

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from 60 patients from Tribe A who had 81 primary dialysis access procedures over a 6 year period, and from 58 patients from Tribe B who had 94 primary dialysis access procedures over a three year period. The authors discuss the types of grafts and fistulas used, and the complications that can be encountered, including thrombosis (clotting), infection, and arterial insufficiency. In the groups covered in this paper, arteriovenous fistulas had a higher initial failure rate than PTFE (polytetrafluoroethylene) grafts in both patient populations, but those that last a year have longer patency than grafts. The primary and secondary patency rates for Tribe B are less than those for Tribe A patients for PTFE grafts. Radiologic thrombectomy with angioplasty has as good results as surgical revisions as a treatment for graft thrombosis. The authors conclude that early placement of access in patients with progressive ESRD reduces the need for temporary access procedures and may reduce the incidence of subclavian vein stenosis. 5 figures. 3 tables. 28 references. •

Diabetes and Heart Disease: New Strategies Emerge Source: Harvard Heart Letter. 10(11): 1-4. July 2000. Contact: Available from Harvard Medical School Health Publications Group. Harvard Heart Letter, P.O. Box 420300, Palm Coast, FL 32142-0300. (800) 829-9045. E-mail: [email protected]. Website: www.health.harvard.edu. Summary: This article explores the relationship between diabetes and cardiovascular disease. Diabetes is a risk factor for atherosclerosis in the blood vessels of the heart and throughout the body. In addition, other risk factors for heart disease are closely associated with diabetes, including obesity, hypertension, and lipid abnormalities. Although the death rates due to coronary heart disease have been steadily declining over the last few decades, this has not been the case for people who have diabetes. Middle aged women with diabetes have the same increased risk for heart disease as do men. In addition, people who have diabetes and have had heart attacks have a less favorable prognosis than heart attack victims without diabetes. Therefore, most experts recommend that physicians regard all people who have diabetes as heart disease patients, even if they show no signs of cardiovascular problems. Studies have shown that beta blockers such as atenolol, metoprolol, nadolol, and propranolol are among the best drugs to treat coronary artery disease. Doctors traditionally have avoided prescribing beta blockers for people who have diabetes because they can mask the warning signs of low blood glucose and can worsen some problems common in people who have diabetes such as impotence and fatigue. However, research suggests that people who have diabetes may derive even greater benefits from beta blockers when compared with people who do not have diabetes. In addition, research suggests that tight diabetes control can reduce the risk of other diabetes complications. Other studies have investigated the outcomes between people with and without diabetes following balloon angioplasty. Results suggest that angioplasty in people who have diabetes leaves more heart muscle in danger than does bypass surgery. Thus, most physicians create treatment plans under the assumption that bypass surgery is the best form of treatment for people who have diabetes and severe symptoms of coronary disease that has not responded to drug treatment.

Academic Periodicals covering Angioplasty Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to angioplasty. In addition to

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these sources, you can search for articles covering angioplasty that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for angioplasty. 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).

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

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to angioplasty by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “angioplasty” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for angioplasty: •

Alprostadil http://www.rarediseases.org/nord/search/nodd_full?code=528

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

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

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

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

•

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/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

12

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

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “angioplasty” (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 33640 325 90 149 39 34243

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 “angioplasty” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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

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

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

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

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

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

•

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

19 Adapted 20

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

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

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

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Other guides Angina http://www.nlm.nih.gov/medlineplus/angina.html Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html

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

General/Overviews Coronary Angiography and Angioplasty http://www.nlm.nih.gov/medlineplus/tutorials/coronaryangiographyandangiopl astyloader.html Coronary Angioplasty: Opening Clogged Arteries Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00485

•

Specific Conditions/Aspects Angioplasty Versus Bypass Surgery for Coronary Artery Disease http://circ.ahajournals.org/cgi/reprint/106/23/e187.pdf Angioplasty, Laser Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4446 Angioplasty, Percutaneous Transluminal Coronary (PTCA) Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4454 FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01257.html

•

From the National Institutes of Health Heart Attack: Special Procedures Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/actintime/aha/spepro.htm

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Latest News Drug-Coated Stents Effective in “Real World” Patients Source: 12/22/2003, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3017894

•

Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/

•

Research Benefits of Coronary Stents Source: American College of Physicians http://www.annals.org/cgi/content/full/138/10/I-15 Brain Angioplasty in Awake Patients May Reduce Complications Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3008843 Enzyme Level Linked to Death after Angioplasty Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3004458 Homocysteine-Lowering Therapy Reduces Risk of Major Adverse Events after Coronary Procedure Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZB4RPQC5D& sub_cat=618 Persistent Smokers Skip Full Benefit of Angioplasty Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3224 Surgery Better Than Drugs for Serious Lack of Blood Flow to the Heart Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3012085 Using Cholesterol-Lowering Medication after Coronary Procedures Reduces the Risk of Subsequent Major Cardiac Events Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZZHNVAZ2D &sub_cat=618

•

Statistics Angioplasty and Cardiac Revascularization Treatments and Statistics Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4439 Angioplasty Safer, Need for Emergency Surgery Afterward Plunges Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3005838

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You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “angioplasty” (or synonyms). The following was recently posted: •

ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines). A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Perc Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 June; 66 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2840&nbr=2066&a mp;string=angioplasties

•

ACR Appropriateness Criteria for recurrent symptoms following lower extremity angioplasty: claudication and threatened limb Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2002); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3561&nbr=2787&a mp;string=angioplasty

•

Coronary angiography and indications for CABG or angioplasty Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 March 27); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3382&nbr=2608&a mp;string=angioplasty Healthfinder™

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

Patient Resources

•

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Devices and Procedures: A Patients' Guide Summary: Useful information for patients about angioplasty procedures and devices technologies, treatments for heart disease. Source: Nonprofit/Professional Entity--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4479 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 angioplasty. 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/

•

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

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

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

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

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

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

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

22

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

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

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

•

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

•

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

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

•

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

•

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

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

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

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

•

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

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

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

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

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

•

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

23

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

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•

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

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

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

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

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

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

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

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

•

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

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

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

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

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

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

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

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

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

•

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

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

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

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•

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

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

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

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

•

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

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

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

•

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/

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

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

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

•

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

•

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

•

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

•

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

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

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

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Angioplasty Angioplasty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002953.htm

•

Signs & Symptoms for Angioplasty Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Problems breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

•

Diagnostics and Tests for Angioplasty Angiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm

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Cardiac catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003419.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Nutrition for Angioplasty Cholesterol Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002472.htm Fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm

•

Surgery and Procedures for Angioplasty CABG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002946.htm Coronary artery bypass graft Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002946.htm

•

Background Topics for Angioplasty Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Stent Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002303.htm

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

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

•

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

•

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

•

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

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ANGIOPLASTY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP

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and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when

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their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amaurosis: Partial or total blindness from any cause. [NIH] Amaurosis Fugax: Partial amaurosis, which is sudden and transitory, and associated with headache, vertigo, and nausea. [NIH] 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 Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH]

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Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Angulation: Deviation from the normal long axis, as in a fractured bone healed out of line. [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]

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Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the development of neoplasms. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Anticardiolipin: Antiphospholipid antibodies found in association with systemic lupus erythematosus (lupus erythematosus, systemic), antiphospholipid syndrome, and in a variety of other diseases as well as in healthy individuals. The antibodies are detected by solid-phase immunoassay employing the purified phospholipid antigen cardiolipin. [NIH] Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome, related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU]

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Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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] Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (antibodies, antiphospholipid). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (antibodies, anticardiolipin). Present also are high levels of lupus anticoagulant (lupus coagulation inhibitor). [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Anuria: Inability to form or excrete urine. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aortic Coarctation: Narrowing of the lumen of the aorta, caused by deformity of the aortic media. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH]

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Aromatic: Having a spicy odour. [EU] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arterial Occlusive Diseases: Diseases in which arterial vessels are partially or completely obstructed or in which the blood flow through the vessels is impeded. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] 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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Arteritis: Inflammation of an artery. [NIH] Articular: Of or pertaining to a joint. [EU] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH]

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Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Vein: The venous trunk of the upper limb; a continuation of the basilar and brachial veins running from the lower border of the teres major muscle to the outer border of the first rib where it becomes the subclavian vein. [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] 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] Balloon Dilatation: Nonoperative repair of occluded vessels, ducts, or valves by insertion of a balloon catheter. It is used, amoung other things, to treat varices, torn retinas, renal and biliary calculi, gastric, bronchial and rectal stenoses, and heart valves, and includes catheterization with Fogarty and Foley catheters. [NIH] Barotrauma: Injury following pressure changes; includes injury to the eustachian tube, ear drum, lung and stomach. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form

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salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a

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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] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bispecific antibodies: Antibodies developed in the laboratory to recognize more than one protein on the surface of different cells. Examples include bispecific antibodies 2B1, 520C9xH22, mDX-H210, and MDX447. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types,

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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 Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachiocephalic Trunk: The first and largest artery branching from the aortic arch. It distributes blood to the right side of the head and neck and to the right arm. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [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] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can

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be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] 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] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH]

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Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac catheterization: A procedure in which a thin, hollow tube is inserted into a blood vessel. The tube is then advanced through the vessel into the heart, enabling a physician to study the heart and its pumping activity. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] Carotid Artery, Internal: Branch of the common carotid artery which supplies the anterior part of the brain, the eye and its appendages, the forehead and nose. [NIH] Carotid Stenosis: The constriction or narrowing of an orifice or the lumen of a hollow or tubular organ. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] 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]

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Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell 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 Cycle Proteins: Proteins that control the cell division cycle. This family of proteins includes a wide variety of classes, including cyclin-dependent kinases, mitogen-activated kinases, cyclins, and phosphoprotein phosphatases (phosphoprotein phosphatase) as well as their putative substrates such as chromatin-associated proteins, cytoskeletal proteins, and transcription factors. [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 Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Movement: The movement of cells from one location to another. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Angiography: Radiography of the vascular system of the brain after injection of a contrast medium. [NIH] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU]

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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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaos: Complex behavior that seems random but actually has some hidden order. [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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH]

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Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] 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] Claudication: Limping or lameness. [EU] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of

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the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such

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as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted

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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] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]

Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] 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]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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 Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH]

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Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarin: A fluorescent dye. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanides: Inorganic salts of hydrogen cyanide containing the -CN radical. The concept also includes isocyanides. It is distinguished from nitriles, which denotes organic compounds containing the -CN radical. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [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] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

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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] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] 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] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes),

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bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH]

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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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diastolic pressure: The lowest pressure to which blood pressure falls between contractions of the ventricles. [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] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilate: Relax; expand. [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] 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] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal

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consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [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] Ego: The conscious portion of the personality structure which serves to mediate between the demands of the primitive instinctual drives, (the id), of internalized parental and social prohibitions or the conscience, (the superego), and of reality. [NIH]

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Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elastomers: A generic term for all substances having the properties of natural, reclaimed, vulcanized, or synthetic rubber, in that they stretch under tension, have a high tensile strength, retract rapidly, and recover their original dimensions fully. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]

Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embolectomy: Surgical removal of an obstructing clot or foreign material which has been transported from a distant vessel by the bloodstream. Removal of a clot at its original site is called thrombectomy. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH]

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Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [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] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopic retrograde cholangiopancreatography: ERCP. A procedure to x-ray the pancreatic duct, hepatic duct, common bile duct, duodenal papilla, and gallbladder. In this procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] 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] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid

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and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enoxaparin: A drug used to prevent blood clots. It belongs to the family of drugs called anticoagulants. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Excimer laser: An ultraviolet laser used in refractive surgery to remove corneal tissue. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams,

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salves, etc. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical,

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characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibrinolytic Agents: Fibrinolysin or agents that convert plasminogen to fibrinolysin (plasmin). [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibromuscular Dysplasia: An idiopathic, segmental, nonatheromatous disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries. Most commonly affected are the renal arteries; involvement of the axillary, iliac, basilar, carotid, hepatic and intracranial arteries have been reported. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but

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if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fractals: Patterns (real or mathematical) which look similar at different scales, for example the network of airways in the lung which shows similar branching patterns at progressively higher magnifications. Natural fractals are self-similar across a finite range of scales while mathematical fractals are the same across an infinite range. Many natural, including

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biological, structures are fractal (or fractal-like). Fractals are related to "chaos" (see nonlinear dynamics) in that chaotic processes can produce fractal structures in nature, and appropriate representations of chaotic processes usually reveal self-similarity over time. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] 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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting

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colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [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

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body. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] 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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half

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of its pharmacologic, physiologic, or radiologic activity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH]

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Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoid: An enlarged or swollen blood vessel, usually located near the anus or the rectum. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [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] Hepatic Duct, Common: Predominantly extrahepatic bile duct which is formed by the junction of the right and left hepatic ducts, which are predominantly intrahepatic, and, in turn, joins the cystic duct to form the common bile duct. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histology: The study of tissues and cells under a microscope. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH]

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Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydration: Combining with water. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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]

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Hyperaemia: An excess of blood in a part; engorgement. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [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] Hyperthyroidism: Excessive functional activity of the thyroid gland. [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] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hysterectomy: Excision of the uterus. [NIH] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileus: Obstruction of the intestines. [EU] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Iliac Vein: A vein on either side of the body which is formed by the union of the external and internal iliac veins and passes upward to join with its fellow of the opposite side to form the inferior vena cava. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Immune response: The activity of the immune system against foreign substances (antigens).

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[NIH]

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

effects

of

foreign

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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] 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

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or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH]

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Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intra-Aortic Balloon Pumping: Counterpulsation in which a pumping unit synchronized with the patient's electrocardiogram rapidly fills a balloon in the aorta with helium or carbon dioxide in early diastole and evacuates the balloon at the onset of systole. As the balloon inflates, it raises aortic diastolic pressure, and as it deflates, it lowers aortic systolic pressure. The result is a decrease in left ventricular work and increased myocardial and

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peripheral perfusion. [NIH] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [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] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH]

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Isosorbide Dinitrate: A vasodilator used in the treatment of angina. Its actions are similar to nitroglycerin but with a slower onset of action. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Jugular Veins: Veins in the neck which drain the brain, face, and neck into the brachiocephalic or subclavian veins. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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 Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinesis: Locomotor behavior not involving a steering reaction, but in which there may be a turning random in direction. It includes orthokinesis, the rate of movement and klinokinesis, the amount of turning, which are related to the intensity of stimulation. [NIH] Kinetic: Pertaining to or producing motion. [EU] Kink: Deviation from the normal long axis, as in a fractured bone healed out of line. [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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH]

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Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Left ventricular assist device: A mechanical device used to increase the heart's pumping ability. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [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] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This

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

Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Local therapy: Treatment that affects cells in the tumor and the area close to it. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH]

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Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [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] Magnetic Resonance Angiography: Non-invasive method of vascular imaging and determination of internal anatomy without injection of contrast media or radiation exposure. The technique is used especially in cerebral angiography as well as for studies of other vascular structures. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU]

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Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] 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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] 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

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animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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]

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Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocular: Diplopia identified with one eye only; it may be induced with a double prism, or it may occur either as a result of double imagery due to an optical defect in the eye, or as a result of simultaneous use of normal and anomalous retinal correspondence. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [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

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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] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] 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] Neck Injuries: General or unspecified injuries to the neck. It includes injuries to the skin, muscles, and other soft tissues of the neck. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis,

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as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [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] Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from cyanides, which denotes inorganic salts of hydrogen cyanide. [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] Nonlinear Dynamics: The study of systems which respond disproportionately (nonlinearly) to initial conditions or perturbing stimuli. Nonlinear systems may exhibit "chaos" which is classically characterized as sensitive dependence on initial conditions. Chaotic systems, while distinguished from more ordered periodic systems, are not random. When their behavior over time is appropriately displayed (in "phase space"), constraints are evident which are described by "strange attractors". Phase space representations of chaotic systems, or strange attractors, usually reveal fractal (fractals) self-similarity across time scales. Natural, including biological, systems often display nonlinear dynamics and chaos. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used

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pharmacologically as a sympathomimetic. [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] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

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Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH]

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Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of

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proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor

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of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoprotein Phosphatase: A group of enzymes removing the serine- or threoninebound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) EC 3.1.3.16. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH]

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Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for

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laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH] 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] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] 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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polytetrafluoroethylene: Homopolymer of tetrafluoroethylene. Nonflammable, tough, inert plastic tubing or sheeting; used to line vessels, insulate, protect or lubricate apparatus; also as filter, coating for surgical implants or as prosthetic material. Synonyms: Fluoroflex; Fluoroplast; Ftoroplast; Halon; Polyfene; PTFE; Tetron. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyurethanes: A group of thermoplastic or thermosetting polymers containing polyisocyanate. They are used as elastomers, as coatings, as fibers and as foams. [NIH] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Popliteal Artery: The continuation of the femoral artery coursing through the popliteal fossa; it divides into the anterior and posterior tibial arteries. [NIH]

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Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prekallikrein: A plasma protein which is the precursor of kallikrein. Plasma that is deficient in prekallikrein has been found to be abnormal in thromboplastin formation, kinin generation, evolution of a permeability globulin, and plasmin formation. The absence of prekallikrein in plasma leads to Fletcher factor deficiency, a congenital disease. [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

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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] Proenzyme: 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] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also).

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The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

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]

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Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulsatile Flow: Rhythmic, intermittent propagation of a fluid through a vessel or piping system, in contrast to constant, smooth propagation, which produces laminar flow. The quality of blood flow, whether smooth (laminar) or pulsatile, is important to the integrity of the tissues being artificially perfused by various heart assist devices or in regional perfusion. [NIH]

Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living

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organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [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] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]

Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiology, Interventional: Subspeciality of radiology that combines organ system

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radiography, catheter techniques and sectional imaging. [NIH] Radionuclide Ventriculography: Imaging of a ventricle of the heart after the injection of a radioactive contrast medium. The technique is less invasive than cardiac catheterization and is used to assess ventricular function. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] 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] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH]

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Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recuperation: The recovery of health and strength. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal Artery Obstruction: Narrowing or occlusion of the renal arteries. It is due usually to atherosclerosis, fibromuscular dysplasia, thrombosis, embolism, or external pressure. It may result in renovascular hypertension. [NIH] Renal Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH]

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Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retractor: An instrument designed for pulling aside tissues to improve exposure at operation; an instrument for drawing back the edge of a wound. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [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] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH]

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Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] 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] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] 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] 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]

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Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequential treatment: One treatment after the other. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the

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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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic

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system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spermine: A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

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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] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] 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] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stethoscopes: An instrument used for the detection and study of sounds within the body that conveyed to the ears of the observer through rubber tubing. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclavian Artery: Artery arising from the brachiocephalic trunk on the right side and from the arch of the aorta on the left side. It distributes to the neck, thoracic wall, spinal cord, brain, meninges, and upper limb. [NIH] Subclavian Vein: The continuation of the axillary vein which follows the subclavian artery and then joins the internal jugular vein to form the brachiocephalic vein. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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]

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Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] 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] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Superior Vena Cava Syndrome: Obstruction of the superior vena cava caused by neoplasm, thrombosis, aneurysm, or external compression and causing suffusion and/or cyanosis of the face, neck, and upper arms. [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] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Affecting the entire body. [NIH]

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Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systole: Period of contraction of the heart, especially of the ventricles. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Systolic pressure: The highest pressure to which blood pressure rises with the contraction of the ventricles. [NIH] 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] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermodilution: Measurement of blood flow based on induction at one point of the circulation of a known change in the intravascular heat content of flowing blood and detection of the resultant change in temperature at a point downstream. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombectomy: Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH]

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Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombolytic Therapy: Use of infusions of fibrinolytic agents to destroy or dissolve thrombi in blood vessels or bypass grafts. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thrombosed: A localized clot that either forms in the vein of a hemorrhoid or arises from a ruptured hemorrhoidal blood vessel. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] 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 Adhesives: Substances used to cause adherence of tissue to tissue or tissue to nontissue surfaces, as for prostheses. [NIH] Tissue Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]

Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

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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] 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] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translating: Conversion from one language to another language. [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] 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] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

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Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Troponin C: One of the three polypeptide chains that make up the troponin complex of skeletal muscle. It is a calcium-binding protein. [NIH] Troponin T: One of the three polypeptide chains that make up the troponin complex. It is a cardiac-specific protein that binds to tropomyosin. It is released from only damaged or injured heart tissue and cells. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unsaturated Fats: A type of fat. [NIH] Untranslated Regions: The parts of the messenger RNA sequence that do not code for

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product, i.e. the 5' untranslated regions and 3' untranslated regions. [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]

Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [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] Vascular Patency: The condition of blood vessels not being blocked or obstructed. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH]

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Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertebral Artery: The first branch of the subclavian artery with distribution to muscles of the neck, vertebrae, spinal cord, cerebellum and interior of the cerebrum. [NIH] Vertebral Artery Dissection: Dissection of the wall of the vertebral artery, leading to the formation of an aneurysm that may occlude the vessel. Thrombus formation may occur and give rise to emboli. Cervical fractures or related neck injuries and craniocerebral trauma are commonly associated conditions, although this process may occur spontaneously. Ischemia, infarction, and hemorrhage in the vascular distribution of the affected vertebral artery may complicate this condition. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [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]

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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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH]

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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]

325

INDEX A Abdomen, 245, 255, 277, 283, 288, 298, 313, 314, 316 Abdominal, 46, 185, 245, 275, 281, 290, 297, 298, 308 Aberrant, 29, 245 Ablation, 33, 76, 86, 107, 149, 245, 306 Acceptor, 245, 287, 296 Acetylcholine, 245, 259, 294 Acetylcholinesterase, 159, 245 Acetylgalactosamine, 245, 277 Acetylglucosamine, 245, 277 Acoustic, 46, 60, 245 Actin, 52, 53, 60, 245, 293, 297, 319 Acute renal, 158, 245 Adaptability, 245, 258 Adaptation, 245, 300 Adenine, 245, 305 Adenosine, 18, 20, 67, 245, 299 Adenovirus, 8, 39, 52, 56, 59, 245 Adenylate Cyclase, 245, 274 Adhesions, 151, 246 Adhesives, 150, 152, 246, 317 Adjunctive Therapy, 43, 94, 108, 246 Adjuvant, 122, 246, 275 Adrenal Glands, 246, 308 Adrenergic, 7, 246, 247, 251, 271, 290, 303 Adsorption, 15, 158, 246 Adsorptive, 246 Adverse Effect, 246, 311 Aerosol, 246, 315 Affinity, 16, 29, 54, 55, 57, 62, 166, 193, 246, 251, 312 Agar, 246, 300 Agonist, 48, 63, 67, 246 Airways, 246, 274 Albumin, 100, 246, 290, 300 Algorithms, 28, 247, 254 Alkaline, 247, 256 Alkaloid, 247, 297 Allergen, 247, 266, 311 Alpha Particles, 247, 306 Alprenolol, 247, 290 Alternative medicine, 119, 128, 214, 247, 261 Aluminum, 166, 247 Alveolar Process, 247, 309 Amaurosis, 185, 247

Amaurosis Fugax, 185, 247 Amino Acid Sequence, 247, 249, 272, 276 Amino Acid Substitution, 193, 247 Amino Acids, 30, 247, 248, 256, 272, 276, 294, 297, 301, 304, 310, 311, 317, 318, 320 Amlodipine, 80, 247 Amplification, 172, 247 Ampulla, 248, 270 Anaesthesia, 248, 283 Analog, 178, 248, 274, 281 Analogous, 11, 55, 248, 318 Anaphylatoxins, 248, 261 Anastomosis, 9, 45, 91, 156, 248 Anatomical, 143, 166, 248, 252, 262, 267, 282, 310 Anemia, 248, 274, 289 Anesthesia, 169, 248, 252, 270 Aneurysm, 70, 101, 185, 193, 248, 250, 315, 321 Angina Pectoris, 100, 114, 134, 137, 168, 172, 185, 197, 204, 247, 248, 290, 303 Angiogenesis, 8, 17, 20, 59, 60, 62, 102, 175, 193, 194, 248, 289 Angiogram, 133, 243, 248 Angiotensinogen, 55, 248, 308 Angulation, 103, 170, 248 Animal model, 8, 10, 16, 17, 23, 24, 36, 39, 40, 48, 51, 52, 56, 57, 114, 141, 248 Anionic, 158, 249 Anions, 246, 249, 285, 315 Ankle, 26, 249 Anorexia, 249, 275, 320 Antagonism, 249, 267 Anterograde, 92, 249 Antibacterial, 249, 313 Antibiotic, 249, 313, 316 Antibiotics, Antineoplastic, 152, 249 Antibodies, 28, 45, 49, 54, 64, 181, 193, 249, 250, 254, 278, 282, 288, 292, 300, 306 Antibodies, Anticardiolipin, 249, 250 Antibodies, Antiphospholipid, 249, 250 Antibody, 28, 88, 94, 141, 181, 246, 249, 261, 271, 278, 279, 282, 283, 285, 290, 292, 306, 307, 311, 313, 322 Anticoagulant, 99, 249, 250, 304, 322 Antigen, 33, 181, 246, 249, 261, 279, 281, 282, 283, 284, 286, 290, 311 Antigen-Antibody Complex, 249, 261

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Antihypertensive, 4, 5, 247, 249, 274 Anti-infective, 250, 280, 312 Anti-inflammatory, 250, 251, 266, 276 Anti-Inflammatory Agents, 250, 251 Antineoplastic, 152, 249, 250, 254, 274, 275, 291, 297 Antineoplastic Agents, 152, 250 Antioxidant, 42, 121, 250, 296 Antiphospholipid Syndrome, 199, 249, 250 Antiproliferative, 18, 51, 119, 178, 250 Antithrombotic, 44, 58, 113, 250 Anuria, 250, 286 Anxiety, 72, 132, 250, 303 Aortic Aneurysm, 46, 185, 250 Aortic Coarctation, 102, 250 Aortic Valve, 101, 250 Apolipoproteins, 250, 287 Apoptosis, 34, 35, 39, 51, 119, 200, 201, 250, 257 Aqueous, 250, 253, 257, 265, 280, 288 Arachidonic Acid, 200, 250, 281, 287, 303 Arginine, 156, 248, 250, 294, 296, 300, 306, 319, 320 Aromatic, 175, 251, 256, 298 Arrestin, 13, 251 Arrhythmia, 251, 321 Arterial Occlusive Diseases, 10, 137, 251 Arteriography, 195, 206, 207, 251 Arteriolar, 251, 255 Arterioles, 180, 251, 254, 256, 291, 293 Arteriolosclerosis, 251 Arteriosclerosis, 90, 159, 168, 172, 175, 251, 263, 281, 292 Arteriovenous, 18, 45, 67, 93, 115, 216, 251, 291 Arteriovenous Fistula, 67, 93, 216, 251 Arteritis, 21, 84, 251 Articular, 251, 296 Aspirin, 41, 44, 63, 124, 137, 204, 251 Assay, 61, 251 Astrocytes, 251, 279 Asymptomatic, 41, 251, 297 Atenolol, 216, 251 Atherectomy, 52, 76, 78, 86, 99, 104, 149, 152, 163, 164, 179, 180, 183, 189, 191, 205, 252, 270 Atrial, 69, 156, 252, 322 Atrial Fibrillation, 156, 252, 322 Atrium, 156, 252, 257, 321 Attenuated, 21, 252 Attenuation, 13, 23, 200, 252

Autodigestion, 252, 297 Autoimmune disease, 185, 199, 249, 252, 292 Autologous, 72, 252 Autonomic, 27, 245, 252, 294, 313, 315 Autonomic Nervous System, 27, 252, 313, 315 Autosuggestion, 252, 281 Axillary, 252, 273, 314 Axillary Vein, 252, 314 B Bacteria, 246, 249, 252, 266, 269, 270, 272, 291, 307, 311, 313, 318, 320 Bacteriophage, 252, 300, 318 Balloon Dilatation, 186, 252 Barotrauma, 84, 252 Base, 40, 160, 245, 252, 266, 271, 273, 276, 286, 316, 320 Basement Membrane, 253, 272 Basophils, 140, 168, 253, 277, 287 Benign, 251, 253, 273, 278, 287, 293, 307 Benign tumor, 253, 287 Beta blocker, 41, 216, 253 Bilateral, 253, 309 Bile, 253, 270, 275, 279, 280, 288 Bile Ducts, 253 Biliary, 157, 252, 253, 256, 297 Biliary Tract, 253, 256, 297 Bilirubin, 246, 253 Binding Sites, 159, 253 Biochemical, 6, 32, 47, 52, 113, 158, 253, 286, 296, 298, 311 Biological therapy, 253, 277 Biological Transport, 253, 267 Biomarkers, 32, 253 Biomechanics, 204, 253 Biophysics, 54, 55, 253 Biopsy, 157, 253, 298 Biosynthesis, 124, 250, 253, 264, 274, 311 Biotechnology, 64, 65, 214, 227, 254 Biotransformation, 254, 298 Biphasic, 62, 254 Bispecific antibodies, 181, 254 Bladder, 254, 275, 292, 304, 320 Bleomycin, 185, 254 Blood Coagulation, 47, 254, 256, 317 Blood Coagulation Factors, 254 Blood Glucose, 216, 254, 278, 284 Blood Platelets, 254, 311 Blood-Brain Barrier, 197, 254 Body Fluids, 253, 254, 255, 268, 312, 319 Bolus, 49, 99, 254

Index

Bolus infusion, 254 Bolus injection, 49, 254 Bone Marrow, 37, 50, 54, 254, 255, 264, 282, 288, 312 Bone Marrow Transplantation, 54, 255 Bone Resorption, 186, 194, 255 Bone scan, 255, 310 Bowel, 140, 167, 168, 255, 267, 283, 298 Bowel Movement, 255, 267 Brachial, 26, 166, 186, 252, 255 Brachiocephalic Trunk, 255, 314 Brachiocephalic Veins, 255, 315 Brachytherapy, 7, 10, 23, 68, 81, 113, 154, 255, 284, 285, 306, 322 Bradykinin, 197, 255, 286, 294, 300 Brain Hypoxia, 255 Brain Infarction, 255 Brain Ischemia, 35, 132, 255 Branch, 102, 103, 142, 143, 162, 241, 255, 257, 269, 288, 297, 298, 305, 308, 313, 316, 321 Breakdown, 255, 267, 275 Bronchial, 252, 255 Bronchitis, 255, 260 Buccal, 255, 288 C Calcification, 184, 251, 255 Calcium channel blocker, 247, 256, 321 Calcium Channels, 256, 297 Calculi, 252, 256 Cannula, 141, 164, 256 Capillary, 180, 255, 256, 321 Capillary Permeability, 255, 256 Carbohydrate, 256, 277, 301 Carbon Dioxide, 256, 265, 274, 284, 309 Carboxy, 256 Carboxylic Acids, 151, 256 Carcinogenic, 256, 283, 295, 303 Carcinogens, 256, 295, 322 Cardiac, 5, 8, 14, 19, 20, 21, 32, 34, 36, 41, 49, 60, 65, 70, 77, 78, 80, 82, 84, 86, 87, 90, 95, 99, 101, 103, 104, 107, 112, 114, 123, 135, 175, 212, 233, 244, 252, 256, 257, 263, 269, 271, 290, 292, 293, 307, 309, 319 Cardiac arrest, 80, 257 Cardiac catheterization, 5, 22, 244, 257, 307 Cardiomyopathy, 75, 232, 257 Cardiopulmonary, 47, 49, 163, 164, 257 Cardiopulmonary Bypass, 47, 49, 163, 164, 257

327

Cardioselective, 251, 257, 303 Cardiovascular disease, 6, 13, 15, 18, 22, 29, 32, 34, 161, 177, 216, 257 Cardiovascular System, 143, 146, 147, 148, 157, 166, 169, 186, 195, 198, 257 Carnitine, 200, 257 Carotid Arteries, 64, 160, 164, 172, 183, 184, 257 Carotid Artery, Internal, 160, 257 Carotid Stenosis, 73, 90, 153, 184, 191, 257 Case report, 70, 82, 87, 92, 93, 104, 108, 257, 260 Caspase, 35, 257 Catecholamines, 12, 257 Cathepsins, 185, 257 Cause of Death, 8, 18, 62, 140, 161, 177, 184, 191, 192, 193, 257 Cell Adhesion, 21, 122, 140, 168, 194, 258, 284 Cell Adhesion Molecules, 21, 122, 258 Cell Cycle, 24, 30, 34, 52, 53, 258, 264, 278, 305 Cell Cycle Proteins, 24, 258 Cell Death, 34, 52, 250, 258, 293 Cell Differentiation, 36, 55, 258, 312 Cell Division, 252, 258, 277, 291, 300 Cell membrane, 60, 253, 256, 258, 266, 299, 302 Cell Movement, 16, 52, 258 Cell Respiration, 258, 309 Cell Survival, 258, 277 Central Nervous System, 191, 199, 245, 252, 256, 258, 275, 278, 280, 287, 292, 296, 311 Cerebellum, 255, 258, 321 Cerebral Angiography, 258, 289 Cerebral Arteries, 258, 291 Cerebrospinal, 157, 258, 280, 311 Cerebrospinal fluid, 157, 258, 280, 311 Cerebrovascular, 71, 94, 112, 191, 257, 258 Cerebrum, 258, 259, 321 Cervical, 98, 259, 321 Cervix, 259 Chaos, 259, 275, 294 Character, 248, 259, 265 Chelation, 34, 114, 123, 127, 259 Chemokines, 16, 21, 259 Chemotactic Factors, 259, 261 Chemotaxis, 6, 16, 185, 259 Chemotherapy, 193, 259 Chest Pain, 204, 259 Chimeras, 16, 259

328

Angioplasty

Cholesterol Esters, 259, 287 Choline, 245, 259 Chorioretinitis, 259, 309 Choroid, 259, 309 Chromatin, 52, 159, 250, 258, 259, 271 Chromosomal, 247, 259 Chromosome, 259, 287 Chronic, 10, 15, 16, 17, 24, 37, 43, 62, 70, 77, 82, 98, 102, 140, 167, 168, 185, 193, 199, 204, 215, 259, 260, 267, 270, 283, 286, 287, 288, 297, 301, 305, 314, 316, 320 Chronic Disease, 15, 37, 259 Chronic Obstructive Pulmonary Disease, 140, 167, 168, 260 Chronic renal, 24, 215, 260, 301, 320 Chylomicrons, 260, 287 Chymopapain, 260, 297 Circulatory system, 172, 260, 270 CIS, 50, 53, 200, 260, 309 Claudication, 26, 105, 172, 234, 260 Climacteric, 197, 260 Clinical study, 260, 263 Clone, 17, 260 Cloning, 35, 254, 260 Clot Retraction, 260, 300 Coagulation, 47, 57, 61, 166, 168, 250, 254, 256, 260, 279, 300, 317, 322 Cofactor, 260, 294, 304, 317 Cohort Studies, 32, 260 Colitis, 261, 283 Collagen, 40, 48, 165, 185, 246, 253, 261, 262, 272, 273, 275, 289, 300, 303 Collagenases, 185, 261 Collapse, 143, 149, 171, 255, 261 Colloidal, 246, 261, 315 Combinatorial, 158, 261 Complement, 11, 12, 26, 57, 94, 248, 261, 276, 284, 300, 311 Complementary and alternative medicine, 119, 128, 261 Complementary medicine, 119, 261 Compress, 146, 169, 198, 262 Computational Biology, 227, 262 Computed tomography, 30, 262, 310 Computerized axial tomography, 262, 310 Computerized tomography, 262 Concomitant, 35, 92, 143, 262 Conduction, 17, 27, 262 Confounding, 5, 7, 262 Confusion, 262, 320 Congestive heart failure, 27, 41, 75, 159, 204, 262

Conjugated, 178, 262, 265 Conjunctiva, 262 Conjunctivitis, 140, 167, 168, 262 Connective Tissue, 250, 255, 261, 262, 273, 275, 288, 309, 316 Connective Tissue Diseases, 250, 262 Consciousness, 262, 268, 309 Constitutional, 262, 292, 309 Constriction, 10, 143, 154, 172, 257, 262, 285, 320 Constriction, Pathologic, 262, 320 Consumption, 263, 266, 275, 296, 309 Contamination, 263, 295 Contractility, 55, 62, 263, 269 Contraindications, ii, 209, 263 Contralateral, 26, 191, 263 Contrast Media, 263, 289 Control group, 5, 31, 263, 302 Controlled clinical trial, 28, 263, 307 Controlled study, 115, 263 Convulsions, 263, 294 Coordination, 193, 258, 263, 292 Coronary Angiography, 17, 40, 102, 135, 204, 232, 263 Coronary Arteriosclerosis, 263, 292 Coronary Circulation, 85, 248, 263, 294 Coronary Disease, 14, 17, 131, 134, 135, 136, 137, 216, 232, 263 Coronary heart disease, 44, 65, 80, 134, 136, 140, 175, 177, 186, 216, 257, 263 Coronary Thrombosis, 263, 290, 292, 293 Coronary Vessels, 263 Cortex, 258, 264, 291 Corticosteroids, 264, 276 Cortisol, 246, 264 Cortisone, 264, 266 Coumarin, 264 Craniocerebral Trauma, 264, 278, 280, 321 Creatinine, 4, 109, 264, 286, 320 Creatinine clearance, 109, 264 Cultured cells, 52, 264 Curative, 264, 316 Cutaneous, 264, 288 Cyanides, 264, 294 Cyanosis, 264, 315 Cyclic, 62, 79, 245, 264, 274, 277, 294, 299, 303 Cyclin, 34, 53, 258, 264 Cyclin-Dependent Kinases, 34, 258, 264 Cyclosporine, 164, 264 Cystathionine beta-Synthase, 264, 281 Cysteine, 185, 259, 260, 264, 270

Index

Cystine, 264 Cytochrome, 200, 265 Cytokine, 49, 265, 284 Cytomegalovirus, 16, 21, 49, 65, 95, 137, 265 Cytoplasm, 250, 253, 258, 265, 270, 271, 277, 310 Cytoskeletal Proteins, 7, 258, 265 Cytoskeleton, 60, 265, 284, 291 Cytostatic, 10, 265 Cytotoxic, 265, 284, 306, 307, 312 Cytotoxicity, 152, 265 D Dairy Products, 265, 310 Databases, Bibliographic, 227, 265 De novo, 55, 70, 265 Decarboxylation, 265, 306 Defense Mechanisms, 265, 284 Degenerative, 265, 279, 296 Deletion, 14, 54, 60, 250, 265 Delivery of Health Care, 266, 278 Density, 61, 266, 268, 287, 288, 301, 313 Dental Caries, 266, 274 Depolarization, 266, 312 Depressive Disorder, 14, 266 Dermatitis, 140, 167, 168, 266 Desensitization, 13, 48, 266 Detergents, 266, 273 Deuterium, 266, 280 Developed Countries, 184, 266 Dexamethasone, 178, 266 Diabetes Mellitus, 60, 77, 103, 131, 134, 199, 203, 215, 266, 276, 278, 284 Diabetic Foot, 203, 204, 266 Diabetic Retinopathy, 140, 167, 168, 266, 299 Diagnostic Imaging, 38, 266 Diagnostic procedure, 139, 189, 215, 266 Dialyzer, 267, 278 Diarrhoea, 267, 275 Diastole, 267, 284 Diastolic, 4, 42, 91, 267, 281, 284 Diastolic blood pressure, 4, 267 Diastolic pressure, 267, 281, 284 Diffusion, 35, 58, 253, 256, 267, 283, 308 Digestion, 253, 255, 267, 288, 314 Digestive system, 138, 267 Dihydrotestosterone, 267, 308 Dilatation, Pathologic, 267, 321 Dilate, 144, 146, 147, 149, 161, 164, 182, 190, 198, 267

329

Dilation, 88, 154, 160, 162, 163, 169, 170, 171, 184, 190, 196, 252, 255, 267, 280, 321 Diltiazem, 81, 267 Dimerization, 30, 267 Dipyridamole, 18, 45, 267 Direct, iii, 28, 35, 69, 73, 75, 80, 86, 87, 90, 152, 159, 177, 186, 267, 297, 308, 314 Disease Progression, 14, 17, 47, 136, 267 Dissection, 67, 78, 82, 104, 108, 148, 267, 321 Dissociation, 246, 267, 285 Diuretic, 268, 285 Dizziness, 193, 268, 321 Dose-dependent, 43, 268 Dosimetry, 23, 113, 268 Double-blinded, 67, 268 Drug Delivery Systems, 7, 15, 268 Drug Interactions, 220, 268 Drug Tolerance, 268, 317 Duct, 154, 182, 248, 256, 257, 268, 270, 279, 310 Duodenum, 253, 268, 270, 297, 314 Dyes, 253, 268 Dyslipidemia, 11, 12, 25, 131, 268 Dysphoric, 266, 268 E Echocardiography, 20, 79, 87, 107, 268 Edema, 266, 268, 286, 293, 305, 320 Effector, 245, 261, 268 Ego, 268, 295 Ejection fraction, 27, 41, 269 Elasticity, 183, 251, 263, 269 Elastin, 261, 262, 269, 272 Elastomers, 187, 269, 301 Elective, 67, 70, 81, 99, 100, 103, 131, 269, 302 Electrocardiogram, 133, 269, 284 Electrocardiography, 27, 269 Electrocoagulation, 260, 269 Electrode, 157, 269 Electrolyte, 269, 286, 302, 312, 320 Electrons, 250, 253, 269, 285, 296, 306, 307 Electrophysiological, 269, 321 Embolectomy, 269, 316 Emboli, 82, 83, 87, 89, 133, 144, 149, 153, 160, 169, 171, 179, 180, 184, 193, 198, 269, 321, 322 Embolism, 47, 58, 83, 104, 132, 184, 269, 305, 308, 322 Embolization, 83, 87, 89, 133, 144, 153, 179, 184, 269, 322 Embolus, 133, 269, 283

330

Angioplasty

Embryo, 258, 269, 282 Emphysema, 193, 260, 269 Empirical, 41, 269 Encapsulated, 15, 270, 288 Encephalopathy, 184, 270 Endarterectomy, 45, 52, 58, 68, 73, 74, 76, 94, 100, 105, 152, 160, 183, 248, 252, 270 Endemic, 270, 289, 313 Endocrine System, 270, 294 Endopeptidases, 257, 270, 298 Endoscope, 270 Endoscopic, 144, 270 Endoscopic retrograde cholangiopancreatography, 144, 270 Endothelial cell, 9, 16, 19, 35, 39, 53, 57, 58, 59, 140, 168, 181, 200, 254, 270, 273, 317, 319 Endothelium, 11, 21, 59, 114, 140, 168, 270, 294, 300, 319 Endothelium, Lymphatic, 270 Endothelium, Vascular, 270 Endothelium-derived, 270, 294 Endotoxic, 270, 287 Endotoxins, 261, 270 End-stage renal, 260, 270, 301 Enhancer, 50, 271, 309 Enoxaparin, 16, 271 Enteropeptidase, 271, 319 Environmental Exposure, 271, 295 Environmental Health, 226, 228, 271 Enzymatic, 57, 172, 256, 261, 264, 266, 271, 273, 297, 309 Eosinophils, 140, 168, 271, 277, 287 Epinephrine, 246, 271, 294, 319 Epithelial, 50, 253, 271, 279 Epithelium, 253, 270, 271 Epitope, 181, 271 Epoprostenol, 271, 281 Erythrocytes, 122, 248, 255, 271, 308, 311 Esophagus, 267, 271, 314, 320 Eukaryotic Cells, 60, 265, 271, 282, 295, 296 Eustachian tube, 252, 271 Excimer laser, 76, 108, 271 Excipients, 271, 301 Excitatory, 272, 294 Excitatory Amino Acids, 272, 294 Excrete, 250, 272, 286 Exhaustion, 249, 272, 289 Exogenous, 60, 246, 254, 272, 276, 304 Exon, 29, 272 Expiration, 272, 309

Extensor, 272, 305 External-beam radiation, 272, 285, 306, 322 Extracellular, 6, 11, 13, 18, 19, 39, 44, 49, 141, 251, 262, 272, 273, 284, 289, 312 Extracellular Matrix, 6, 11, 19, 39, 141, 262, 272, 273, 284, 289 Extracellular Matrix Proteins, 272, 289 Extracellular Space, 272 Extracorporeal, 191, 272 Extravascular, 57, 172, 272 Extremity, 26, 84, 147, 174, 184, 196, 234, 272 Eye Infections, 245, 272 F Facial, 5, 272, 313 Family Planning, 227, 272 Fat, 159, 244, 250, 255, 263, 269, 272, 287, 292, 295, 301, 309, 310, 312, 319 Fatigue, 216, 272, 278 Fatty acids, 55, 120, 123, 124, 136, 246, 256, 273, 303, 312, 317 Femoral Artery, 26, 40, 70, 93, 97, 104, 114, 150, 152, 169, 173, 183, 213, 257, 273, 301 Femur, 273 Fibrin, 37, 47, 57, 152, 194, 254, 260, 273, 300, 316, 317 Fibrinogen, 14, 273, 300, 316 Fibrinolysis, 11, 12, 26, 60, 85, 194, 212, 273 Fibrinolytic, 37, 55, 57, 65, 66, 77, 79, 87, 104, 106, 273, 317 Fibrinolytic Agents, 273, 317 Fibroblast Growth Factor, 17, 19, 273 Fibroblasts, 7, 52, 186, 273 Fibroid, 273, 287 Fibromuscular Dysplasia, 273, 308 Fibrosis, 7, 140, 155, 167, 168, 193, 273, 310 Fibula, 273, 301 Fish Oils, 121, 123, 135, 273 Fistula, 18, 45, 87, 93, 251, 273 Fixation, 273, 311 Flatus, 274, 275 Fluorescence, 22, 274 Fluorine, 157, 274 Fluoroscopy, 82, 150, 157, 173, 274 Fluorouracil, 267, 274 Flush, 183, 274 Flushing, 183, 274 Folate, 112, 274 Fold, 13, 21, 144, 214, 274, 290 Folic Acid, 274

Index

Foot Ulcer, 203, 266, 274 Forearm, 46, 254, 274, 307 Forskolin, 63, 274 Fossa, 258, 274, 301 Fractals, 142, 274, 294 Friction, 150, 275 Fundus, 185, 275, 295 Fungi, 272, 275, 291, 323 G Gadolinium, 38, 132, 133, 136, 275 Gallbladder, 245, 253, 267, 270, 275 Gamma Rays, 275, 306, 307 Gamma-interferon, 275, 284 Ganglia, 245, 255, 275, 293, 315 Gangrene, 184, 275 Gas, 146, 178, 213, 256, 267, 274, 275, 280, 294, 315 Gastric, 252, 257, 275 Gastrin, 275, 279 Gastroenteritis, 49, 275 Gastrointestinal, 140, 143, 167, 168, 255, 271, 273, 275, 287, 289, 311, 313, 314, 315, 319 Gastrointestinal tract, 273, 275, 287, 311, 314, 319 Gelatin, 275, 277, 316 Gelatinases, 185, 275 Gels, 151, 152, 275 Gene Expression, 11, 12, 22, 26, 29, 30, 50, 52, 53, 54, 59, 132, 276 Gene Targeting, 6, 276 Generator, 33, 276 Genetic Code, 276, 295 Genetic Engineering, 254, 260, 276 Genetic Markers, 73, 276 Genetics, 15, 32, 44, 276, 298 Genotype, 46, 212, 276, 298 Gland, 264, 273, 274, 276, 281, 288, 297, 299, 304, 311, 314, 317 Glomerular, 276, 286, 308 Glomeruli, 276 Glomerulonephritis, 140, 167, 168, 185, 276 Glucocorticoid, 8, 49, 266, 276 Glucose, 81, 84, 215, 216, 254, 266, 276, 277, 278, 283, 284 Glucose Intolerance, 266, 276 Glucuronic Acid, 276, 279 Glycine, 159, 277, 311 Glycolysis, 43, 277 Glycoprotein, 61, 69, 82, 88, 100, 273, 277, 317

331

Glycosaminoglycans, 51, 272, 277 Glycoside, 277, 280 Glycosidic, 277, 295 Governing Board, 277, 302 Grade, 14, 70, 109, 277 Grafting, 24, 65, 67, 86, 93, 120, 182, 204, 205, 213, 263, 277, 282 Granule, 277, 310 Granulocytes, 277, 312, 322 Gravis, 199, 277 Groin, 159, 195, 277, 283 Growth factors, 13, 19, 35, 37, 42, 47, 141, 165, 185, 194, 204, 277 Guanylate Cyclase, 39, 277, 294 H Haematoma, 277 Haemorrhage, 112, 277 Half-Life, 16, 33, 187, 277, 281 Haptens, 246, 278 Headache, 247, 278, 280 Health Behavior, 32, 278 Health Care Costs, 33, 204, 278 Health Expenditures, 278 Health Status, 278 Heart attack, 51, 89, 105, 106, 107, 159, 161, 172, 212, 216, 257, 278 Heart failure, 15, 18, 27, 41, 69, 75, 106, 159, 197, 204, 262, 278 Heart Transplantation, 15, 278 Heart Valves, 252, 278 Helix-loop-helix, 30, 278 Heme, 253, 265, 278 Hemodialysis, 4, 9, 18, 24, 42, 45, 46, 77, 86, 200, 215, 267, 278, 286 Hemodynamics, 46, 278 Hemoglobin, 49, 248, 264, 271, 278 Hemorrhage, 35, 63, 108, 112, 113, 264, 266, 269, 278, 279, 293, 305, 314, 321, 322 Hemorrhoid, 279, 317 Hemostasis, 279, 284, 311 Heparan Sulfate Proteoglycan, 19, 279 Heparin, 19, 51, 88, 103, 112, 113, 125, 165, 166, 212, 279 Hepatic, 247, 270, 273, 279, 288 Hepatic Duct, Common, 270, 279 Hepatitis, 49, 197, 279 Hepatocytes, 279 Hereditary, 59, 262, 279, 309 Heredity, 276, 279 Heterodimer, 39, 279 Heterogeneity, 246, 279 Histology, 48, 119, 279

332

Angioplasty

Homeobox, 184, 279 Homeostasis, 13, 279, 313 Homologous, 276, 279, 311, 315 Homotypic, 47, 279 Hormonal, 33, 279 Hormonal therapy, 33, 279 Hormone, 29, 80, 133, 204, 264, 271, 275, 279, 280, 284, 300, 309, 312, 316, 317 Hormone Replacement Therapy, 204, 279 Hormone therapy, 80, 279, 280 Host, 50, 165, 193, 252, 280, 282, 287, 322 Humoral, 7, 59, 65, 280 Humour, 280 Hybrid, 30, 114, 260, 280 Hydration, 16, 280 Hydrocephalus, 280, 285 Hydrogel, 152, 280 Hydrogen, 187, 245, 253, 256, 264, 266, 272, 280, 287, 291, 294, 296, 298, 304, 315 Hydrogen Cyanide, 264, 280, 294 Hydrogen Peroxide, 187, 280, 287, 315 Hydrolases, 200, 270, 280, 298, 299 Hydrolysis, 245, 254, 280, 298, 299, 301, 304, 319 Hydrophilic, 102, 161, 165, 266, 280 Hydrophobic, 161, 266, 280, 287 Hydroxylysine, 261, 280 Hydroxyproline, 261, 280 Hyperaemia, 262, 281 Hypercholesterolemia, 268, 281 Hyperglycemia, 131, 281 Hyperhomocysteinemia, 92, 264, 281 Hyperlipidemia, 268, 281 Hyperplasia, 9, 10, 12, 15, 18, 24, 34, 38, 42, 45, 48, 52, 56, 58, 145, 156, 165, 281 Hypersensitivity, 247, 266, 281, 287, 309, 311 Hyperthyroidism, 281, 303 Hypertriglyceridemia, 268, 281 Hypertrophy, 7, 54, 281 Hypotensive, 281, 286 Hypothalamus, 252, 281, 299 Hysterectomy, 47, 281 I Iatrogenic, 78, 281 Id, 116, 126, 232, 234, 235, 240, 242, 268, 281 Ileus, 197, 281 Iliac Artery, 152, 183, 273, 281 Iliac Vein, 152, 183, 281 Illusion, 121, 281, 321 Iloprost, 115, 281

Immune response, 199, 246, 249, 252, 264, 278, 281, 282, 311, 315, 322 Immune system, 14, 199, 253, 281, 282, 287, 288, 289, 292, 320, 322 Immunity, 185, 199, 282, 284, 295 Immunization, 282, 303, 311 Immunocompromised, 21, 282 Immunogenic, 282, 287 Immunoglobulin, 249, 282, 292 Immunohistochemistry, 63, 282 Immunologic, 259, 282, 307 Immunology, 16, 246, 282 Immunosuppressive, 178, 276, 282, 316 Immunotherapy, 253, 266, 282 Impairment, 112, 272, 282, 290 Implant radiation, 282, 284, 285, 306, 322 Implantation, 64, 77, 81, 91, 135, 143, 146, 165, 178, 190, 282 Impotence, 216, 282, 297 In situ, 6, 55, 63, 142, 151, 282 In Situ Hybridization, 63, 282 In vitro, 7, 9, 10, 16, 22, 30, 37, 39, 42, 45, 47, 51, 52, 53, 56, 57, 63, 103, 282, 316 Incision, 142, 143, 160, 178, 282, 285 Incubation, 151, 282 Indicative, 43, 59, 204, 282, 297, 320 Induction, 8, 52, 59, 62, 141, 282, 284, 316 Infancy, 19, 283 Inferior vena cava, 92, 281, 283 Infertility, 197, 283, 286 Infiltration, 276, 283 Inflammatory bowel disease, 140, 167, 168, 283 Infusion, 79, 84, 112, 113, 134, 155, 169, 212, 254, 283, 293 Ingestion, 274, 283, 301 Inguinal, 75, 101, 283 Initiation, 43, 283, 303, 318 Inlay, 283, 309 Inorganic, 170, 264, 283, 294 Inositol, 48, 283 Inotropic, 74, 251, 283 Inpatients, 84, 283 Insecticides, 283, 322 Insight, 19, 21, 37, 47, 61, 284 Insulator, 284, 292 Insulin, 11, 12, 25, 81, 84, 131, 204, 284 Insulin-dependent diabetes mellitus, 284 Integrins, 36, 194, 284 Intercellular Adhesion Molecule-1, 140, 168, 284 Interleukin-1, 109, 284

Index

Interleukin-18, 109, 284 Interleukin-2, 284 Intermittent, 105, 172, 284, 288, 298, 305 Internal radiation, 284, 285, 306, 322 Interstitial, 23, 255, 272, 284, 285, 308, 322 Intestines, 245, 260, 267, 275, 281, 284 Intoxication, 284, 322 Intra-Aortic Balloon Pumping, 81, 284 Intracellular, 19, 34, 43, 48, 56, 59, 63, 283, 284, 285, 294, 302, 303, 307, 312 Intraocular, 274, 285 Intraocular pressure, 274, 285 Intravascular, 7, 23, 37, 40, 42, 61, 86, 144, 145, 146, 147, 148, 150, 164, 165, 167, 169, 170, 172, 180, 186, 188, 192, 205, 285, 316 Intravenous, 20, 87, 96, 99, 108, 133, 254, 283, 285 Intrinsic, 13, 246, 253, 285 Intubation, 257, 285 Involuntary, 285, 293, 312 Ion Channels, 159, 251, 285 Ionization, 285 Ionizing, 10, 39, 155, 158, 247, 271, 285, 307 Ions, 253, 256, 267, 269, 280, 285, 302, 304 Irradiation, 10, 84, 86, 87, 122, 155, 187, 190, 285, 322 Ischemic stroke, 63, 285 Isosorbide, 90, 211, 285, 286 Isosorbide Dinitrate, 90, 211, 286 J Joint, 196, 251, 286, 296, 315, 316 Jugular Veins, 48, 286 K Kallidin, 197, 255, 286 Kallikreins, 197, 286 Kb, 226, 286 Kidney Disease, 33, 131, 132, 138, 215, 226, 286 Kidney Failure, 161, 270, 286 Kidney Failure, Acute, 286 Kidney Failure, Chronic, 286 Kinesis, 16, 286 Kinetic, 47, 285, 286 Kink, 148, 150, 286 L Labile, 261, 286 Large Intestine, 267, 284, 286, 307, 308, 312 Latency, 50, 286 Latent, 21, 57, 287, 302 Left ventricular assist device, 15, 287 Leiomyoma, 47, 273, 287

333

Length of Stay, 109, 287 Leprosy, 274, 287 Leukemia, 13, 287 Leukocytes, 37, 58, 140, 168, 253, 255, 259, 271, 277, 287 Leukotrienes, 250, 287 Library Services, 240, 287 Life cycle, 50, 254, 275, 287 Ligament, 287, 304 Ligands, 16, 37, 44, 258, 284, 287 Ligation, 43, 194, 287 Linkage, 188, 276, 287 Lipid, 20, 26, 34, 216, 250, 251, 256, 259, 284, 287, 288, 292, 296 Lipid A, 216, 287 Lipid Peroxidation, 287, 296 Lipopolysaccharide, 49, 287 Lipoprotein, 10, 61, 94, 268, 287, 288 Liposomal, 16, 134, 287 Liposome, 15, 288 Liver, 41, 197, 245, 247, 250, 253, 257, 265, 267, 273, 274, 275, 276, 279, 288, 307, 310, 320 Liver Cirrhosis, 197, 288 Liver scan, 288, 310 Local therapy, 9, 288 Localization, 19, 197, 282, 288 Localized, 17, 28, 255, 266, 270, 274, 277, 283, 288, 300, 317, 319 Long-Term Care, 38, 288 Loop, 30, 193, 278, 288 Low-density lipoprotein, 61, 268, 287, 288 Lupus, 140, 167, 168, 199, 249, 250, 288, 316 Lymph, 252, 259, 260, 270, 280, 288 Lymph node, 252, 259, 288 Lymphatic, 179, 270, 283, 288, 312, 313, 317 Lymphatic system, 288, 313, 317 Lymphocyte, 14, 249, 288, 290 Lymphocyte Count, 14, 288 Lymphoid, 249, 264, 288 Lysine, 280, 289, 319 Lysosome, 186, 289 M Macrophage, 54, 186, 284, 289 Magnetic Resonance Angiography, 30, 38, 157, 289 Magnetic Resonance Imaging, 17, 26, 38, 132, 133, 136, 157, 289, 310 Malaria, 185, 289 Malaria, Falciparum, 289

334

Angioplasty

Malaria, Vivax, 289 Malignant, 27, 199, 250, 251, 289, 293, 307 Malnutrition, 247, 289 Mammary, 92, 263, 289 Mammogram, 256, 289, 291 Mandible, 247, 289, 309 Manifest, 160, 289 Matrix metalloproteinase, 79, 289 Meat, 289, 310 Medial, 52, 62, 155, 195, 251, 289 Mediate, 16, 28, 37, 39, 59, 165, 194, 258, 268, 289 Mediator, 284, 290, 311 Medical Oncology, 290, 306 Medical Staff, 268, 290 Medicament, 144, 200, 290 MEDLINE, 227, 290 Melanin, 290, 299, 319 Membrane Glycoproteins, 256, 290, 302 Memory, 144, 249, 290 Meninges, 258, 264, 290, 314 Menopause, 290, 302, 303 Mental Disorders, 138, 290, 302 Mental Health, iv, 6, 138, 226, 228, 290, 303, 305 Mesenteric, 104, 184, 290 Mesentery, 290, 298 Meta-Analysis, 65, 66, 70, 107, 123, 290 Metabolite, 254, 290, 303, 307 Metastasis, 185, 193, 194, 258, 289, 290 Metastatic, 194, 290, 311 Metoprolol, 216, 290 MI, 20, 27, 32, 40, 43, 75, 92, 212, 213, 214, 244, 290 Microbe, 290, 318 Microbiology, 16, 49, 204, 245, 291 Microcalcifications, 256, 291 Microcirculation, 58, 288, 291, 300 Microorganism, 260, 291, 297, 322 Microscopy, 83, 253, 291, 295 Microspheres, 196, 291 Microtubules, 159, 291, 297 Microwaves, 291, 306 Middle Cerebral Artery, 35, 84, 291 Millimeter, 23, 291 Mitochondrial Swelling, 291, 293 Mitosis, 250, 291 Mitoxantrone, 165, 291 Mobility, 30, 291 Modeling, 36, 46, 55, 89, 103, 291 Modification, 26, 28, 41, 59, 276, 291, 306 Monitor, 22, 38, 42, 61, 264, 292, 295

Monoclonal, 49, 54, 141, 285, 292, 306, 322 Monoclonal antibodies, 49, 54, 292 Monocular, 109, 292 Monocyte, 37, 49, 68, 84, 292 Mononuclear, 141, 292 Morphological, 52, 269, 292 Morphology, 26, 29, 292 Motility, 292, 311 Mucosa, 288, 292 Multicenter study, 131, 292 Multiple sclerosis, 140, 167, 168, 199, 292 Muscle Fibers, 292, 293, 319 Mutagenesis, 17, 30, 37, 55, 292 Mutagenic, 200, 292 Mutagens, 292 Myasthenia, 199, 292 Mydriatic, 267, 292 Myelin, 292 Myocardial Ischemia, 17, 57, 100, 102, 120, 134, 135, 136, 137, 154, 197, 248, 263, 292 Myocardial Reperfusion, 87, 89, 97, 293, 308 Myocardial Reperfusion Injury, 293, 308 Myocardium, 17, 27, 36, 43, 57, 74, 155, 248, 290, 292, 293 Myosin, 50, 55, 293, 319 N Nausea, 247, 275, 293, 320 NCI, 1, 138, 225, 260, 293 Neck Injuries, 293, 321 Necrosis, 43, 184, 250, 255, 283, 290, 292, 293, 308 Neoplasm, 293, 315, 319 Nephropathy, 49, 100, 286, 293 Nephrotoxic, 158, 293 Nerve, 204, 246, 248, 290, 292, 293, 294, 295, 296, 299, 301, 302, 309, 310, 314, 318 Nervous System, 27, 191, 199, 245, 252, 256, 258, 275, 278, 280, 287, 290, 292, 293, 294, 296, 311, 313, 315 Neural, 280, 293 Neuroendocrine, 59, 294 Neurologic, 30, 191, 280, 294, 318 Neuromuscular, 245, 294, 320 Neuromuscular Junction, 245, 294 Neuroprotective Agents, 191, 294 Neuroretinitis, 294, 309 Neutrons, 247, 285, 294, 306 Neutrophil, 47, 54, 193, 284, 294 Nickel, 166, 294 Nitric Oxide, 11, 39, 90, 98, 294 Nitriles, 185, 264, 294

Index

Nitroglycerin, 286, 294 Nonlinear Dynamics, 275, 294 Norepinephrine, 246, 294 Nuclear, 17, 43, 113, 155, 269, 271, 275, 293, 295 Nuclei, 157, 247, 269, 276, 289, 291, 294, 295, 296, 304 Nucleic acid, 52, 193, 276, 282, 292, 295, 305, 313 Nucleolus, 295, 310 Nucleotidases, 280, 295 Nucleus, 250, 252, 253, 259, 264, 265, 266, 271, 275, 292, 294, 295, 304, 313, 314 O Obsession, 106, 295 Ocular, 71, 185, 295 Odour, 251, 295, 320 Oligosaccharides, 16, 295 Oliguria, 286, 295 Omega-3 fatty acid, 124, 295 Oncogene, 13, 295, 297, 305 Oncogenic, 284, 295, 305 Operon, 295, 303, 308 Opium, 295, 297 Opportunistic Infections, 21, 295 Optic Disk, 266, 295 Optic Nerve, 294, 295, 296, 309 Organ Transplantation, 19, 296 Organelles, 265, 296 Ornithine, 296, 306 Osmotic, 246, 285, 291, 296 Osteoarthritis, 185, 296 Osteoclasts, 185, 296 Osteoporosis, 175, 185, 194, 296 Outpatient, 22, 296 Ovulation, 194, 296 Ovum, 287, 296 Oxidation, 135, 245, 250, 254, 264, 265, 287, 296 Oxidative Stress, 42, 84, 296 Oxygen Consumption, 296, 309 Oxygenation, 108, 296 Oxygenator, 163, 257, 296 P Paclitaxel, 9, 45, 178, 297 Palliative, 297, 316 Pancreas, 245, 253, 267, 284, 297, 319 Pancreatic, 257, 270, 297 Pancreatic Ducts, 270, 297 Pancreatitis, 197, 297 Papain, 185, 297 Papaverine, 112, 113, 115, 295, 297

335

Papilla, 270, 297 Paroxysmal, 248, 297 Particle, 26, 288, 297, 313, 318 Patch, 94, 100, 105, 107, 297 Pathogen, 14, 282, 297 Pathogenesis, 21, 37, 47, 51, 201, 297 Pathologic, 11, 36, 151, 160, 250, 253, 262, 263, 267, 281, 297, 305, 309, 320, 321 Pathologic Processes, 250, 297 Pathologies, 199, 200, 297 Pathophysiology, 6, 29, 43, 204, 297 Patient Selection, 69, 297 Pelvic, 47, 297, 304 Peptide, 7, 29, 54, 55, 56, 69, 75, 193, 194, 261, 270, 271, 273, 275, 280, 297, 298, 300, 301, 304 Peptide Hydrolases, 270, 280, 298 Perfusion, 8, 17, 20, 35, 62, 99, 154, 163, 180, 191, 207, 285, 298, 305 Periodontitis, 5, 298 Perioperative, 57, 298 Peritoneal, 215, 298 Peritoneal Cavity, 298 Peritoneal Dialysis, 215, 298 Peritoneum, 290, 298 Perivascular, 9, 45, 298 Peroxide, 187, 280, 287, 298, 315 Petechiae, 277, 298 PH, 23, 298 Pharmacodynamics, 103, 298 Pharmacogenetics, 44, 298 Pharmacokinetic, 33, 298 Pharmacologic, 15, 40, 204, 248, 278, 298, 318 Phenotype, 13, 46, 49, 298 Phenyl, 140, 167, 298 Phenylalanine, 298, 319 Phorbol, 299, 304 Phorbol Esters, 299, 304 Phospholipases, 299, 312 Phospholipids, 249, 250, 272, 283, 287, 299, 304 Phosphoprotein Phosphatase, 258, 299 Phosphoric Monoester Hydrolases, 280, 299 Phosphorus, 256, 299 Phosphorylated, 13, 251, 299 Phosphorylates, 299, 304 Phosphorylation, 13, 62, 264, 299 Photocoagulation, 260, 299 Photodynamic therapy, 213, 299 Photosensitizer, 179, 299

336

Angioplasty

Phototransduction, 251, 299 Physical Examination, 132, 136, 299 Physiologic, 11, 37, 57, 59, 246, 253, 260, 266, 278, 299, 303, 307, 309 Physiology, 7, 37, 45, 49, 54, 185, 204, 245, 257, 269, 299 Pilot study, 20, 32, 43, 113, 299 Pituitary Gland, 273, 274, 299 Plants, 247, 256, 259, 276, 277, 292, 294, 300, 301, 318, 319 Plasma cells, 249, 300 Plasma Kallikrein, 197, 286, 300 Plasma protein, 246, 270, 300, 302, 304 Plasmin, 55, 193, 273, 300, 302, 317, 320 Plasminogen, 35, 55, 57, 60, 126, 193, 273, 300, 317, 320 Plasminogen Activators, 56, 57, 194, 300 Plasticity, 53, 300 Platelet Activation, 81, 300, 312 Platelet Aggregation, 44, 61, 248, 271, 274, 281, 294, 300, 317 Platelet-Derived Growth Factor, 13, 300 Platelets, 16, 44, 47, 58, 68, 171, 254, 294, 300, 311, 316, 317 Platinum, 288, 300 Pneumonitis, 49, 301 Poisoning, 275, 284, 293, 301 Polycystic, 33, 301 Polyethylene, 37, 144, 301 Polyethylene Glycols, 37, 301 Polymerase, 43, 301, 303, 308 Polymers, 151, 152, 156, 161, 170, 187, 301, 304 Polymorphic, 44, 301 Polymorphism, 10, 44, 301 Polypeptide, 8, 247, 261, 273, 300, 301, 303, 319, 323 Polysaccharide, 166, 249, 301 Polytetrafluoroethylene, 45, 216, 301 Polyunsaturated fat, 120, 136, 301, 317 Polyurethanes, 187, 301 Popliteal, 46, 101, 143, 180, 301 Popliteal Artery, 101, 301 Port, 120, 141, 147, 177, 183, 191, 302 Port-a-cath, 302 Posterior, 258, 259, 297, 301, 302 Postmenopausal, 80, 296, 302 Postsynaptic, 302, 312 Potassium, 81, 84, 114, 212, 302, 312 Potassium Channels, 212, 302 Potentiates, 37, 60, 284, 302 Potentiation, 302, 312

Practicability, 302, 318 Practice Guidelines, 228, 234, 302 Precipitation, 199, 302 Preclinical, 15, 302 Precursor, 248, 250, 259, 268, 271, 294, 298, 300, 302, 303, 304, 313, 319 Predisposition, 199, 302 Prekallikrein, 300, 302 Prevalence, 44, 302 Primary endpoint, 11, 12, 25, 302 Primary Prevention, 18, 302 Probe, 49, 303 Prodrug, 303, 307 Proenzyme, 193, 303 Progression, 4, 11, 12, 14, 15, 17, 26, 30, 34, 43, 46, 47, 50, 132, 136, 201, 206, 248, 264, 267, 303 Progressive, 52, 114, 159, 216, 251, 258, 260, 268, 277, 286, 293, 296, 300, 303, 308, 319 Projection, 142, 265, 294, 296, 303 Proline, 261, 280, 303 Promoter, 29, 50, 52, 303 Promotor, 303, 309 Prone, 54, 123, 160, 303 Prophylaxis, 303, 322 Proportional, 33, 176, 303 Propranolol, 216, 251, 303 Prospective Studies, 27, 303 Prostaglandin, 123, 133, 271, 303, 317 Prostaglandins A, 303, 304 Prostate, 33, 253, 286, 304, 319 Prosthesis, 145, 146, 148, 304 Protease, 55, 57, 60, 186, 304, 317 Protein Binding, 30, 304 Protein C, 16, 99, 197, 246, 247, 250, 252, 287, 304, 319, 320 Protein Kinase C, 60, 304 Protein Kinases, 54, 59, 304 Protein S, 56, 59, 62, 254, 276, 304, 310, 316 Proteolytic, 197, 261, 271, 273, 286, 297, 300, 304, 317, 320 Prothrombin, 304, 316 Protocol, 11, 12, 26, 61, 112, 133, 304 Protons, 247, 280, 285, 304, 306 Proto-Oncogene Proteins, 297, 305 Proto-Oncogene Proteins c-mos, 297, 305 Psoriasis, 140, 168, 305 Psychic, 260, 305 Public Health, 35, 228, 305 Public Policy, 227, 305 Publishing, 64, 305

Index

Pulmonary, 47, 57, 98, 107, 140, 156, 167, 168, 254, 260, 263, 271, 278, 286, 287, 305, 321, 322 Pulmonary Artery, 254, 305, 321 Pulmonary Edema, 286, 305 Pulmonary Embolism, 47, 305, 322 Pulmonary hypertension, 98, 271, 305 Pulsatile Flow, 74, 305 Pulse, 292, 305 Pupil, 267, 292, 305 Purines, 305, 311 Purpura, 277, 305 Putrefaction, 275, 305, 306 Putrescine, 158, 306, 313 Q Quality of Life, 11, 12, 14, 20, 25, 28, 32, 41, 89, 105, 132, 213, 306 Quiescent, 24, 306 R Race, 204, 291, 306 Radiation Oncology, 8, 306 Radiation therapy, 7, 9, 33, 272, 284, 285, 306, 322 Radio Waves, 132, 133, 291, 306 Radiofrequency ablation, 107, 306 Radiography, 248, 258, 263, 306, 307 Radioimmunotherapy, 306, 307 Radioisotope, 189, 306 Radiolabeled, 285, 306, 322 Radiological, 28, 298, 306 Radiologist, 28, 38, 207, 306 Radiology, 22, 23, 24, 28, 34, 38, 46, 71, 74, 75, 82, 83, 91, 92, 93, 98, 101, 104, 114, 115, 164, 234, 306 Radiology, Interventional, 164, 306 Radionuclide Ventriculography, 40, 307 Radiopharmaceutical, 276, 307 Radiotherapy, 23, 255, 285, 306, 307, 322 Radius, 176, 307 Ramipril, 114, 307 Randomized clinical trial, 85, 307 Randomized Controlled Trials, 66, 307 Reactive Oxygen Species, 34, 47, 159, 307 Receptors, Serotonin, 307, 311 Recombinant, 48, 50, 99, 307, 321 Recombination, 276, 307 Rectal, 252, 307 Rectum, 255, 267, 274, 275, 279, 283, 286, 304, 307, 308 Recuperation, 160, 308 Recurrence, 121, 162, 200, 308 Red blood cells, 57, 271, 308

337

Reductase, 18, 308 Refer, 1, 255, 261, 268, 274, 275, 288, 294, 306, 308 Refraction, 308, 313 Refractory, 75, 269, 308 Regeneration, 37, 273, 308 Regimen, 20, 26, 33, 268, 308 Registries, 134, 308 Relaxant, 274, 297, 308 Remission, 308 Renal Artery, 4, 5, 38, 46, 72, 75, 95, 100, 103, 112, 132, 152, 183, 209, 308 Renal Artery Obstruction, 72, 132, 308 Renal Dialysis, 41, 46, 308 Renal failure, 24, 158, 184, 215, 301, 308, 320 Renin, 248, 308 Renovascular, 93, 308 Reperfusion, 8, 19, 27, 32, 34, 35, 40, 43, 57, 69, 80, 87, 89, 97, 113, 140, 167, 168, 293, 308 Reperfusion Injury, 34, 140, 167, 168, 293, 308 Repressor, 24, 50, 295, 308 Resorption, 186, 194, 255, 280, 296, 309 Respiration, 43, 256, 258, 292, 309 Response Elements, 8, 309 Restoration, 43, 56, 293, 308, 309, 322 Resuscitation, 72, 309 Reticular, 142, 309 Retina, 259, 266, 294, 296, 299, 309, 310, 320 Retinal, 251, 266, 292, 295, 296, 299, 309 Retinitis, 49, 309 Retinoblastoma, 24, 309 Retractor, 176, 309 Retrograde, 28, 101, 144, 270, 309 Retrospective, 71, 88, 93, 309 Rheumatism, 309 Rheumatoid, 37, 185, 194, 195, 199, 309 Rheumatoid arthritis, 37, 185, 194, 195, 199, 309 Rhinitis, 140, 167, 168, 197, 309 Ribose, 43, 245, 310 Ribosome, 29, 310, 318 Rigidity, 150, 300, 310 Risk factor, 5, 17, 20, 31, 32, 41, 44, 58, 109, 131, 216, 281, 310 Risk patient, 27, 32, 73, 74, 76, 163, 164, 204, 310 Rod, 171, 310 Rubber, 269, 310, 314

338

Angioplasty

S Saline, 28, 170, 310 Salivary, 265, 267, 310 Salivary glands, 265, 267, 310 Saphenous, 48, 90, 105, 153, 184, 263, 310 Saphenous Vein, 48, 90, 105, 153, 184, 263, 310 Saturated fat, 159, 310 Scans, 17, 35, 133, 310 Schizoid, 310, 322 Schizophrenia, 310, 322 Schizotypal Personality Disorder, 310, 322 Sclerosis, 16, 21, 140, 167, 168, 199, 251, 292, 310 Screening, 5, 260, 310 Secondary tumor, 290, 311 Secretion, 194, 280, 284, 311 Semen, 304, 311 Senile, 296, 311 Sensitization, 11, 12, 25, 131, 311 Sensor, 42, 101, 136, 311 Sequence Homology, 24, 311 Sequencing, 54, 311 Sequential treatment, 145, 311 Serine, 13, 55, 193, 264, 270, 286, 299, 304, 305, 311, 317, 319 Serotonin, 47, 307, 311, 319 Serous, 270, 311 Serum, 4, 26, 30, 56, 62, 215, 246, 248, 261, 286, 288, 311 Shedding, 49, 311 Shock, 54, 127, 311, 318 Shunt, 157, 311 Side effect, 219, 221, 246, 253, 311, 318 Signal Transduction, 10, 14, 39, 54, 61, 192, 199, 283, 312 Silicon, 36, 312 Silicon Dioxide, 312 Skeletal, 312, 319 Skeleton, 245, 273, 286, 303, 312 Skull, 132, 264, 312, 316 Small intestine, 253, 260, 268, 270, 279, 284, 312, 319 Sneezing, 311, 312 Soaps, 273, 312 Social Environment, 20, 306, 312 Sodium, 35, 123, 271, 299, 312 Soft tissue, 204, 254, 293, 312 Solid tumor, 194, 248, 254, 312 Solitary Nucleus, 252, 313 Somatic, 260, 280, 291, 313 Sound wave, 262, 306, 313

Soybean Oil, 301, 313 Spatial disorientation, 268, 313 Specialist, 236, 267, 313 Species, 34, 47, 152, 159, 271, 275, 280, 289, 291, 292, 296, 306, 307, 311, 313, 314, 318, 319, 322 Specificity, 13, 16, 55, 63, 246, 256, 270, 313, 315 Spectrum, 40, 291, 306, 313 Spermidine, 158, 313 Spermine, 158, 313 Spinal cord, 251, 255, 258, 259, 290, 293, 294, 313, 314, 315, 321 Spleen, 265, 288, 313 Sporadic, 309, 313 Stabilization, 8, 28, 313 Staging, 310, 313 Statistically significant, 5, 314 Steel, 28, 62, 144, 166, 182, 314 Sterile, 155, 314 Sterility, 283, 314 Steroids, 264, 276, 314 Stethoscopes, 46, 314 Stimulant, 286, 314 Stimulus, 263, 269, 285, 286, 314, 316 Stomach, 245, 252, 267, 271, 275, 279, 284, 293, 298, 312, 313, 314 Strand, 43, 301, 314 Stress, 14, 17, 20, 42, 84, 243, 252, 264, 274, 275, 293, 296, 302, 309, 310, 314 Subacute, 283, 314 Subarachnoid, 108, 112, 113, 278, 314 Subclavian, 92, 108, 183, 216, 252, 255, 286, 314, 321 Subclavian Artery, 92, 314, 321 Subclavian Vein, 183, 216, 252, 255, 286, 314 Subclinical, 283, 314 Subcutaneous, 125, 268, 287, 314 Subspecies, 313, 314 Substance P, 290, 311, 315 Substrate, 13, 55, 62, 186, 189, 280, 315 Substrate Specificity, 55, 315 Suction, 36, 170, 315 Superior vena cava, 152, 183, 255, 315 Superior Vena Cava Syndrome, 152, 183, 315 Superoxide, 11, 90, 315 Superoxide Dismutase, 90, 315 Supplementation, 120, 122, 126, 315 Support group, 41, 315 Suppression, 10, 24, 59, 124, 315

Index

Survival Rate, 191, 315 Suspensions, 60, 152, 315 Sympathetic Nervous System, 252, 315 Symphysis, 304, 315 Symptomatic, 26, 33, 47, 63, 70, 73, 82, 103, 113, 191, 297, 315 Synaptic, 312, 315 Synergistic, 9, 18, 44, 315 Synovial, 186, 315 Systemic disease, 199, 316 Systemic lupus erythematosus, 249, 250, 316 Systole, 284, 316 Systolic, 4, 42, 88, 281, 284, 316 Systolic blood pressure, 42, 316 Systolic pressure, 284, 316 T Tacrolimus, 178, 316 Temporal, 35, 47, 50, 62, 157, 316 Teratogenic, 267, 316 Testosterone, 308, 316 Tetracycline, 53, 316 Therapeutics, 66, 103, 220, 316 Thermodilution, 28, 316 Thigh, 273, 277, 316 Thoracic, 67, 81, 107, 115, 314, 316, 322 Thorax, 245, 315, 316 Threonine, 13, 299, 304, 305, 311, 316 Threshold, 35, 186, 281, 316 Thrombectomy, 25, 86, 87, 149, 180, 216, 269, 316 Thrombin, 47, 48, 56, 273, 300, 304, 316, 317 Thrombocytes, 300, 316 Thromboembolism, 57, 317 Thrombolytic, 27, 47, 56, 64, 89, 96, 97, 300, 317 Thrombolytic Therapy, 27, 64, 89, 96, 97, 317 Thrombomodulin, 304, 317 Thrombopenia, 250, 317 Thrombosed, 25, 67, 86, 317 Thromboses, 24, 168, 175, 250, 317 Thromboxanes, 250, 317 Thrombus, 44, 58, 79, 83, 153, 179, 184, 263, 283, 285, 292, 293, 300, 317, 321 Thymus, 282, 288, 317 Thyroid, 199, 281, 317, 319 Thyroxine, 246, 299, 317 Tin, 114, 300, 317 Tissue Adhesives, 152, 317 Tissue Extracts, 186, 317

339

Tissue Plasminogen Activator, 35, 317 Tolerance, 114, 245, 268, 276, 317 Tomography, 30, 262, 310, 318 Topical, 280, 297, 312, 318 Torsion, 283, 318 Toxic, iv, 60, 197, 265, 271, 280, 282, 293, 306, 318 Toxicity, 39, 49, 268, 318 Toxicology, 33, 228, 318 Toxins, 249, 256, 270, 276, 283, 292, 306, 318 Trace element, 274, 294, 312, 317, 318 Trachea, 317, 318 Transcription Factors, 24, 258, 309, 318 Transduction, 10, 14, 39, 54, 59, 61, 192, 199, 283, 312, 318 Transfection, 23, 30, 254, 318 Transgenes, 8, 56, 318 Transient Ischemic Attacks, 127, 185, 318 Translating, 21, 318 Translation, 52, 318 Translational, 29, 318 Transmitter, 245, 251, 272, 285, 290, 294, 318 Transplantation, 15, 19, 54, 79, 101, 140, 167, 168, 255, 260, 278, 282, 286, 296, 318 Trauma, 49, 61, 93, 143, 156, 160, 178, 189, 264, 278, 280, 293, 294, 297, 318, 321 Treatment Outcome, 32, 318 Tropism, 59, 319 Tropomyosin, 319 Troponin, 101, 114, 319 Troponin C, 319 Troponin T, 101, 319 Trypsin, 55, 271, 303, 319, 323 Tryptophan, 261, 311, 319 Tuberculosis, 34, 263, 288, 319 Tubulin, 291, 319 Tumor marker, 253, 319 Tumour, 168, 319 Tunica Intima, 270, 319 Tyrosine, 6, 13, 16, 59, 257, 319 U Ulcer, 274, 319 Ulceration, 184, 204, 319 Ultrasonography, 100, 319 Unconscious, 265, 281, 319 Unsaturated Fats, 273, 319 Untranslated Regions, 29, 319 Uraemia, 297, 320 Urea, 286, 296, 320 Uremia, 42, 286, 308, 320

340

Angioplasty

Ureters, 144, 308, 320 Urethra, 304, 320 Urinary, 256, 280, 295, 317, 320 Urinary Plasminogen Activator, 317, 320 Urine, 250, 254, 264, 268, 286, 295, 320 Urokinase, 55, 57, 60, 194, 320 Uterus, 259, 273, 275, 281, 287, 320 Uveitis, 251, 320 V Vaccine, 246, 304, 320 Vagina, 259, 320 Vaginal, 197, 320 Valves, 101, 164, 252, 278, 320 Varices, 252, 320 Vascular endothelial growth factor, 8, 22, 102, 320 Vascular Patency, 146, 320 Vasculitis, 297, 320 Vasoactive, 133, 320 Vasoconstriction, 12, 271, 320 Vasodilatation, 286, 321 Vasodilation, 12, 281, 297, 321 Vasodilator, 62, 255, 286, 293, 297, 321 Vasomotor, 11, 321 Vector, 8, 28, 59, 62, 318, 321 Vena, 92, 152, 183, 255, 281, 283, 315, 321 Venous, 9, 13, 28, 43, 45, 78, 91, 153, 163, 179, 250, 251, 252, 255, 294, 304, 321, 322 Venous Thrombosis, 321, 322 Ventricle, 97, 250, 281, 305, 307, 316, 321 Ventricular Dysfunction, 269, 321 Ventricular Function, 17, 27, 76, 81, 86, 100, 109, 307, 321 Ventricular Remodeling, 88, 321 Venules, 254, 256, 270, 291, 321 Verapamil, 121, 321

Vertebrae, 313, 321 Vertebral, 31, 68, 82, 109, 179, 321 Vertebral Artery, 82, 179, 321 Vertebral Artery Dissection, 82, 321 Vertigo, 110, 247, 321 Veterinary Medicine, 172, 227, 321 Viral, 16, 21, 50, 59, 140, 168, 295, 318, 321 Virulence, 252, 318, 322 Virus, 51, 252, 271, 276, 300, 318, 321, 322 Visceral, 252, 298, 322 Visceral Afferents, 252, 322 Viscosity, 176, 322 Vitamin A, 283, 322 Vitreous Hemorrhage, 266, 322 Vitro, 7, 9, 10, 16, 22, 30, 37, 38, 39, 42, 45, 47, 51, 52, 53, 56, 57, 63, 103, 279, 282, 316, 322 Vivo, 6, 7, 10, 13, 16, 22, 29, 33, 37, 40, 42, 45, 48, 52, 53, 56, 57, 59, 62, 67, 103, 172, 279, 282, 316, 317, 322 W Warfarin, 63, 322 White blood cell, 249, 287, 288, 289, 292, 294, 300, 322 Windpipe, 317, 322 Withdrawal, 63, 322 Wound Healing, 37, 47, 189, 204, 258, 273, 284, 289, 322 X Xenobiotics, 200, 322 Xenograft, 33, 248, 322 X-ray therapy, 285, 322 Y Yeasts, 275, 298, 323 Z Zymogen, 172, 303, 304, 323

Index

341

342

Angioplasty

Index

343

344

Angioplasty

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