The Official Patient's Sourcebook on Primary Pulmonary Hypertension

THE OFFICIAL PATIENT’S SOURCEBOOK

on

PRIMARY

PULMONARY HYPERTENSION 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 Ó2002 by ICON Group International, Inc. Copyright Ó2002 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: Tiffany LaRochelle 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 as a substitute for consultation with your physician. All matters regarding your health require medical supervision. 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, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking 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., 1960The Official Patient’s Sourcebook on Primary Pulmonary Hypertension: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83154-8 1. Primary Pulmonary Hypertension-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 or as a substitute for consultation with licensed medical professionals. 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, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. 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 sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of primary pulmonary hypertension.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to primary pulmonary hypertension. All of the Official Patient’s Sourcebooks 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 sourcebook. 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 LaRochelle 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 the Official Patient’s Sourcebook series published 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 the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to primary pulmonary hypertension, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Asthma

·

The Official Patient's Sourcebook on Bronchopulmonary Dysplasia

·

The Official Patient's Sourcebook on Chronic Obstructive Pulmonary Disease

·

The Official Patient's Sourcebook on Cystic Fibrosis

·

The Official Patient's Sourcebook on Idiopathic Pulmonary Fibrosis

·

The Official Patient's Sourcebook on Pulmonary Lymphangioleiomyomatosis

·

The Official Patient's Sourcebook on Respiratory Failure

·

The Official Patient's Sourcebook on Sarcoidosis

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

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON PRIMARY PULMONARY HYPERTENSION: GUIDELINES ............................................................... 9

Overview............................................................................................................... 9 What Is Primary Pulmonary Hypertension?..................................................... 11 Incidence ............................................................................................................. 12 Causes of PPH .................................................................................................... 12 Course of the Disease .......................................................................................... 13 Symptoms ........................................................................................................... 13 Diagnosis ............................................................................................................ 14 Treatment............................................................................................................ 17 The Primary Pulmonary Hypertension Patient Registry, 1981-1988............... 19 Living with Primary Pulmonary Hypertension................................................. 20 For More Information......................................................................................... 20 More Guideline Sources ..................................................................................... 21 Vocabulary Builder............................................................................................. 26

CHAPTER 2. SEEKING GUIDANCE ....................................................... 31

Overview............................................................................................................. 31 Associations and Primary Pulmonary Hypertension ........................................ 31 Finding More Associations................................................................................. 35 Finding Doctors.................................................................................................. 37 Selecting Your Doctor ........................................................................................ 38 Working with Your Doctor ................................................................................ 39 Broader Health-Related Resources ..................................................................... 40 Vocabulary Builder............................................................................................. 41

CHAPTER 3. CLINICAL TRIALS AND PRIMARY PULMONARY HYPERTENSION.................................................................................... 43

Overview............................................................................................................. 43 Recent Trials on Primary Pulmonary Hypertension ......................................... 46 Benefits and Risks............................................................................................... 50 Keeping Current on Clinical Trials.................................................................... 53 General References.............................................................................................. 54 Vocabulary Builder............................................................................................. 55

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 57 CHAPTER 4. STUDIES ON PRIMARY PULMONARY HYPERTENSION .... 59

Overview............................................................................................................. 59 The Combined Health Information Database ..................................................... 59 Federally-Funded Research on Primary Pulmonary Hypertension................... 60 E-Journals: PubMed Central .............................................................................. 73 The National Library of Medicine: PubMed ...................................................... 73 Vocabulary Builder............................................................................................. 74

CHAPTER 5. BOOKS ON PRIMARY PULMONARY HYPERTENSION ...... 81

Overview............................................................................................................. 81 Book Summaries: Online Booksellers ................................................................. 81 The National Library of Medicine Book Index ................................................... 82 Chapters on Primary Pulmonary Hypertension ................................................ 85 Directories........................................................................................................... 86 General Home References ................................................................................... 87 Vocabulary Builder............................................................................................. 88 CHAPTER 6. MULTIMEDIA ON PRIMARY PULMONARY

HYPERTENSION................................................................................ 89

Overview............................................................................................................. 89 Bibliography: Multimedia on Primary Pulmonary Hypertension..................... 89 Vocabulary Builder............................................................................................. 92

CHAPTER 7. PERIODICALS AND NEWS ON PRIMARY PULMONARY HYPERTENSION.................................................................................... 93

Overview............................................................................................................. 93 News Services & Press Releases ......................................................................... 93 Newsletter Articles ........................................................................................... 100 Academic Periodicals covering Primary Pulmonary Hypertension ................ 101 Vocabulary Builder........................................................................................... 102

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ................... 105

Overview........................................................................................................... 105 NIH Guidelines................................................................................................. 105 NIH Databases.................................................................................................. 108 Other Commercial Databases ........................................................................... 113 The Genome Project and Primary Pulmonary Hypertension .......................... 114 Specialized References....................................................................................... 118 Vocabulary Builder........................................................................................... 119

CHAPTER 9. DISSERTATIONS ON PRIMARY PULMONARY HYPERTENSION.................................................................................. 121

Overview........................................................................................................... 121 Dissertations on Primary Pulmonary Hypertension ....................................... 121 Keeping Current ............................................................................................... 122

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PART III. APPENDICES .................................................. 123 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 125

Overview........................................................................................................... 125 Your Medications: The Basics .......................................................................... 126 Learning More about Your Medications .......................................................... 128 Commercial Databases...................................................................................... 130 Contraindications and Interactions (Hidden Dangers) ................................... 132 A Final Warning .............................................................................................. 132 General References............................................................................................ 133 Vocabulary Builder........................................................................................... 134

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 135

Overview........................................................................................................... 135 What Is CAM? ................................................................................................. 135 What Are the Domains of Alternative Medicine?............................................ 136 Can Alternatives Affect My Treatment? ......................................................... 139 Finding CAM References on Primary Pulmonary Hypertension ................... 140 Additional Web Resources................................................................................ 141 General References............................................................................................ 144

APPENDIX C. RESEARCHING NUTRITION ......................................... 147

Overview........................................................................................................... 147 Food and Nutrition: General Principles........................................................... 147 Finding Studies on Primary Pulmonary Hypertension................................... 152 Federal Resources on Nutrition........................................................................ 156 Additional Web Resources................................................................................ 157 Vocabulary Builder........................................................................................... 158

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 161

Overview........................................................................................................... 161 Preparation ....................................................................................................... 161 Finding a Local Medical Library ...................................................................... 162 Medical Libraries Open to the Public............................................................... 162

APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 169

Overview........................................................................................................... 169 Your Rights as a Patient................................................................................... 169 Patient Responsibilities .................................................................................... 173 Choosing an Insurance Plan............................................................................. 174 Medicare and Medicaid .................................................................................... 177 NORD’s Medication Assistance Programs ..................................................... 180 Additional Resources ........................................................................................ 180 Vocabulary Builder........................................................................................... 181

ONLINE GLOSSARIES.................................................... 183 Online Dictionary Directories.......................................................................... 188

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PRIMARY PULMONARY HYPERTENSION GLOSSARY ......................................................................... 189 General Dictionaries and Glossaries ................................................................ 204

INDEX................................................................................... 206

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, 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.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

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Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Primary Pulmonary Hypertension has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to primary pulmonary hypertension, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on primary pulmonary hypertension. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on primary pulmonary hypertension should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique.

Introduction

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Deciding on appropriate options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching primary pulmonary hypertension (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to primary pulmonary hypertension. It also gives you sources of information that can help you find a doctor in your local area specializing in treating primary pulmonary hypertension. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with primary pulmonary hypertension. Part II moves on to advanced research dedicated to primary pulmonary hypertension. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on primary pulmonary hypertension. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with primary pulmonary hypertension or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with primary pulmonary hypertension. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with primary pulmonary hypertension.

Scope While this sourcebook covers primary pulmonary hypertension, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that primary pulmonary hypertension is often considered a synonym or a condition closely related to the following:

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Primary Pulmonary Hypertension

·

Familial Primary Pulmonary Hypertension

·

Idiopathic Pulmonary Hypertension

·

Primary Obliterative Pulmonary Vascular Disease

·

Primary Pulmonary Vascular Disease

·

Pulmonary Hypertension

In addition to synonyms and related conditions, physicians may refer to primary pulmonary hypertension using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for primary pulmonary hypertension:4 ·

416.0 primary pulmonary hypertension

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to primary pulmonary hypertension. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

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recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with primary pulmonary hypertension will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with primary pulmonary hypertension is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. Before beginning your search for information, it is important for you to realize that primary pulmonary hypertension is considered a relatively uncommon condition. Because of this, far less research is conducted on primary pulmonary hypertension compared to other health problems afflicting larger populations, like breast cancer or heart disease. Nevertheless, this sourcebook will prove useful for two reasons. First, if more information does become available on primary pulmonary hypertension, the sources given in this book will be the most likely to report or make such information available. Second, some will find it important to know about patient support, symptom management, or diagnostic procedures that may be relevant to both primary pulmonary hypertension and other conditions. By using the sources listed in the following chapters, self-directed research can be conducted on broader topics that are related to primary pulmonary hypertension but not readily uncovered using general Internet search engines (e.g. www.google.com or www.yahoo.com). In this way, we have designed this sourcebook to complement these general search engines that can provide useful information and access to online patient support groups.5 While we focus on the more scientific aspects of primary pulmonary hypertension, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give For example, one can simply go to www.google.com, or other general search engines (e.g. www.yahoo.com, www.aol.com, www.msn.com) and type in “diseasex support group” to find any active online support groups dedicated to diseasex.

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Primary Pulmonary Hypertension

you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

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PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on primary pulmonary hypertension. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of primary pulmonary hypertension to you or even given you a pamphlet or brochure describing primary pulmonary hypertension. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON PRIMARY PULMONARY HYPERTENSION: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on primary pulmonary hypertension. 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. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on primary pulmonary hypertension 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.

The National Institutes of Health (NIH)6 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on primary pulmonary hypertension. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians.

6

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

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Among them are 97 scientists who have won the Nobel Prize for achievement in medicine. There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with primary pulmonary hypertension and associated conditions: ·

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

·

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

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines at http://www.nhlbi.nih.gov/guidelines/index.htm

Among these, the National Heart, Lung, and Blood Institute (NHLBI) is particularly noteworthy. The NHLBI provides leadership for a national program in diseases of the heart, blood vessels, lung, and blood; blood resources; and sleep disorders.7 Since October 1997, the NHLBI has also had administrative responsibility for the NIH Woman’s Health Initiative. The Institute plans, conducts, fosters, and supports an integrated and coordinated program of basic research, clinical investigations and trials, observational studies, and demonstration and education projects. Research is related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The NHLBI plans and directs research in development and evaluation of interventions and devices related to prevention, treatment, and rehabilitation of patients suffering from such diseases and disorders. It also supports research on clinical use of blood and all aspects of the management of blood resources. Research is conducted in the Institute’s own laboratories and by scientific institutions and individuals supported by research grants and contracts. For health professionals and the public, the NHLBI conducts educational activities, including development and dissemination of materials in the above areas, with an emphasis on prevention.

This paragraph has been adapted from the NHLBI: http://www.nhlbi.nih.gov/about/org/mission.htm. “Adapted” signifies that a passage is reproduced exactly or slightly edited for this book. 7

Guidelines 11

Within the NHLBI, the Division of Lung Diseases (DLD) maintains surveillance over developments in pulmonary research and assesses the Nation’s need for research on the causes, prevention, diagnosis, and treatment of pulmonary diseases.8 Also within the purview of the Division are: technology development, application of research findings, and research training and career development in pulmonary diseases. The DLD plans and directs the research and training programs which encompass basic research, applied research and development, clinical investigations, clinical trials, and demonstration and education research. Two programs comprise the Division of Lung Diseases, Airway Biology and Disease Program, and the Lung Biology and Disease Program. The following patient guideline was recently published by the NHLBI and the DLD on primary pulmonary hypertension.

What Is Primary Pulmonary Hypertension?9 Primary, or unexplained, pulmonary hypertension (PPH) is a rare lung disorder in which the blood pressure in the pulmonary artery rises far above normal levels for no apparent reason. The pulmonary artery is the blood vessel carrying oxygen-poor blood from the right ventricle, one of the pumping chambers of the heart, to the lungs. In the lungs, the blood picks up oxygen and then flows to the left side of the heart, where it is pumped by the left ventricle to the rest of the body through the aorta. Hypertension is the medical term for an abnormally high blood pressure. Normal mean pulmonary-artery pressure is approximately 14 mm Hg at rest. In the PPH patient, the mean blood pressure in the pulmonary artery is greater than 25 mm Hg at rest and 30 mm Hg during exercise. This abnormally high pressure (pulmonary hypertension) is associated with changes in the small blood vessels in the lungs, resulting in an increased resistance to blood flowing through the vessels. This increased resistance, in turn, places a strain on the right ventricle, which now has to work harder than usual against the resistance to move adequate amounts of blood through the lungs.

Adapted from the DLD: http://www.nhlbi.nih.gov/about/dld/index.htm. For more information, contact: Division of Lung Diseases; National Heart, Lung and Blood Institute; ATTN: Web Site Inquiries; Two Rockledge Center, Suite 10122, 6701 Rockledge Dr., MSC 7952; Bethesda, Maryland 20892-7952. 9 Adapted from The National Heart Lung and Blood Institute: http://www.nhlbi.nih.gov/health/public/lung/other/pph_doc.htm. 8

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Incidence The true incidence of PPH is unknown. The first reported case occurred in 1891, when E. Romberg, a German doctor, published a description of a patient who, at autopsy, showed thickening of the pulmonary artery but no heart or lung disease that might have caused the condition. In 1951, when 39 cases were reported by Dr. D.T. Dresdale in the United States, the illness received its name. Between 1967 and 1973, a 10-fold increase in unexplained pulmonary hypertension was reported in central Europe. The rise was subsequently traced to aminorex fumarate, an amphetamine-like drug introduced in Europe in 1965 to control appetite. Only about 1 in 1,000 people who took the drug developed PPH. When they stopped taking the drug, some improved considerably; in others, the disease kept getting worse. Once aminorex was removed from the market, the incidence of PPH went down to normal levels. More recently, in the United States and France, several cases of PPH have been associated with the appetite suppressants, fenfluramine and dexfenfluramine. In the United States it has been estimated that 300 new cases of PPH are diagnosed each year; the greatest number are reported in women between the ages of 21 and 40. Indeed, at one time the disease was thought to occur among young women almost exclusively; we now know, however, that men and women in all age ranges, from very young children to elderly people, can develop PPH. Apparently it also affects people of all racial and ethnic origins equally.

Causes of PPH There may be one or more causes of PPH; however, all remain unknown. The low incidence makes learning more about the disease extremely difficult. Studies of PPH also have been difficult because a good animal model of the disease has not been available. Researchers think that in most people who develop PPH the blood vessels are particularly sensitive to certain internal or external factors and constrict, or narrow, when exposed to these factors. For example, people with Raynaud’s disease seem more likely than others to develop PPH; Raynaud’s

Guidelines 13

disease is a condition in which the fingers and toes turn blue when cold because the blood vessels in the fingers and toes are particularly sensitive to cold. Diet suppressants, cocaine, HIV, and pregnancy are some of the factors that are thought to trigger constriction, or narrowing, in the pulmonary artery. In about 6 to 10 percent of cases, PPH is familial; that is, it is inherited from other family members. The familial form of PPH is similar to the more common form of the disease, sometimes referred to as “sporadic” PPH.

Course of the Disease Researchers believe that one of the ways PPH starts is with injury to the layer of cells (the endothelial cells) that line the small blood vessels of the lungs. This injury, which occurs for unknown reasons, may bring about changes in the way the endothelial cells interact with smooth muscle cells in the vessel wall. As a result, the smooth muscle contracts more than normal and thereby narrows the vessel. The process eventually results in the development of extra amounts of tissue in the walls of the pulmonary arteries. The amount of muscle increases in some arteries, and muscle appears in the walls of arteries that normally have no muscle. With time, scarring, or fibrosis, of the arteries takes place, and they become stiff as well as thickened. Some vessels may become completely blocked. There is also a tendency for blood clots to form within the smaller arteries. In response to the extra demands placed on it by PPH, the heart muscle gets bigger, and the right ventricle expands in size. Overworked and enlarged, the right ventricle gradually becomes weak and loses its ability to pump enough blood to the lungs. Eventually, the right side of the heart may fail completely, resulting in death.

Symptoms In general, researchers find there is no correlation between the time PPH is thought to have started, the age at which it is diagnosed, and the severity of symptoms. In some patients, especially children, the disease progresses fairly rapidly.

14 Primary Pulmonary Hypertension

The first symptom is frequently tiredness, with many patients thinking they tire easily because they are simply out of shape. Difficulty in breathing (dyspnea), dizziness, and even fainting spells (syncope) are also typical early symptoms. Swelling in the ankles or legs (edema), bluish lips and skin (cyanosis), and chest pain (angina) are among other symptoms of the disease. Patients with PPH may also complain of a racing pulse; many feel they have trouble getting enough air. Palpitations, a strong throbbing sensation brought on by the increased rate of the heartbeat, can also cause discomfort. Some people with PPH do not seek medical advice until they can no longer go about their daily routine. The more severe the symptoms, the more advanced the disease. In these more advanced stages, the patient is able to perform only minimal activity and has symptoms even when resting. The disease may worsen to the point where the patient is completely bedridden.

Diagnosis PPH is rarely picked up in a routine medical examination. Even in its later stages, the signs of the disease can be confused with other conditions affecting the heart and lungs. Thus, much time can pass between the time the symptoms of PPH appear and a definite diagnosis is made. The first tests for PPH help the doctor determine how well the heart and lungs are performing. If the results of these tests do not give the doctor enough information, the doctor must perform a cardiac catheterization. The procedure, discussed below, is the way the doctor can make certain that the patient’s problems are due to PPH and not to some other condition. PPH remains a diagnosis of exclusion. This means that it is diagnosed only after the doctor finds pulmonary hypertension and excludes or cannot find other reasons for the hypertension, such as a chronic obstructive pulmonary disease (chronic bronchitis and emphysema), blood clots in the lung (pulmonary thromboemboli), or some forms of congenital heart disease.

Electrocardiogram The electrocardiogram (ECG) is a record of the electrical activity produced by the heart. An abnormal ECG may indicate that the heart is undergoing unusual stress. In addition to the usual ECG performed while the patient is at rest, the doctor may order an exercise ECG. This ECG helps the doctor

Guidelines 15

evaluate the performance of the heart during exercise, for example, walking a treadmill in the doctor’s office.

Echocardiogram In an echocardiogram, the doctor uses sound waves to map the structure of the heart by placing a slim device that looks like a microphone on the patient’s chest. The instrument sends sound waves into the heart, which then are reflected back to form a moving image of the beating heart’s structure on a TV screen. A record is made on paper or videotape. The moving pictures show how well the heart is functioning. The still pictures permit the doctor to measure the size of the heart and the thickness of the heart muscle; in the patient with severe pulmonary hypertension, the still pictures will show that the right heart is enlarged, while the left heart is either normal or reduced in size. Echocardiograms are helpful in excluding some other causes of pulmonary hypertension and can be useful in monitoring the response to treatment.

Pulmonary Function Tests A variety of tests called pulmonary function tests (PFTs) evaluate lung function. In these procedures, the patient, with a nose clip in place, breathes in and out through a mouthpiece. The patient’s breathing displaces the air held in a container suspended in water. As the container rises and falls in response to the patient’s breathing, the movements produce a record, or spirogram, that helps the doctor measure lung volume (how much air the lungs hold) and the air flow in and out of the lungs. Some devices measure air flow electronically. A mild restriction in air movement is commonly seen in patients with PPH. This restriction is thought to be due, in part, to the increased stiffness of the lungs resulting from both the changes in the structure and the high blood pressure in the pulmonary arteries. Perfusion Lung Scan A perfusion lung scan shows the pattern of blood flow in the lungs; it can also tell the doctor whether a patient has large blood clots in the lungs. In the perfusion scan, the doctor injects a radioactive substance into a vein. Immediately after the injection, the chest is scanned for radioactivity. Areas

16 Primary Pulmonary Hypertension

in the lung where blood clots are blocking the flow of blood will show up as blank or clear areas. Two patterns of pulmonary perfusion are seen in patients with PPH. One is a normal pattern of blood distribution; the other shows a scattering of patchy abnormalities in blood flow. A major reason for doing a perfusion scan is to distinguish patients with PPH from those whose pulmonary hypertension is due to blood clots in the lungs.

Right-Heart Cardiac Catheterization In right-heart cardiac catheterization, the doctor places a thin, flexible tube, or catheter, through an arm, leg, or neck vein in the patient, and then threads the catheter into the right ventricle and pulmonary artery. Most important in terms of PPH is the ability of the doctor to get a precise measure of the blood pressure in the right side of the heart and the pulmonary artery with this procedure. It is the only way to get this measure, and must be performed in the hospital by a specialist. During catheterization, the doctor can also evaluate the right heart’s pumping ability; this is done by measuring the amount of blood pumped out of the right side of the heart with each heartbeat.

Functional Classification Once PPH is diagnosed, most doctors will classify the disease according to the functional classification system developed by the New York Heart Association. It is based on patient reports of how much activity they can comfortably undertake. ·

Class 1--Patients with no symptoms of any kind, and for whom ordinary physical activity does not cause fatigue, palpitation, dyspnea, or anginal pain.

·

Class 2--Patients who are comfortable at rest but have symptoms with ordinary physical activity.

·

Class 3--Patients who are comfortable at rest but have symptoms with less-than-ordinary effort.

·

Class 4--Patients who have symptoms at rest.

Guidelines 17

Treatment Some patients do well by taking medicines that make the work of the right ventricle easier. Anticoagulants, for example, can decrease the tendency of the blood to clot, thereby permitting blood to flow more freely. Diuretics decrease the amount of fluid in the body, further reducing the amount of work the heart has to do. Until recently, nothing more could be done for people who have PPH. However, today doctors can choose from a variety of drugs that help lower blood pressure in the lungs and improve the performance of the heart in many patients. Some patients also require supplemental oxygen delivered through nasal prongs or a mask if breathing becomes difficult; some need oxygen around the clock. In severely affected cases, a heart-lung, single lung, or double lung transplantation may be appropriate. Drugs Doctors now know that PPH patients respond differently to the different medicines that dilate, or relax, blood vessels and that no one drug is consistently effective in all patients. Because individual reactions vary, different drugs have to be tried before chronic or long-term treatment begins. During the course of the disease, the amount and type of medicine may also have to be changed. To find out which medicine works best for a particular patient, doctors evaluate the drugs during cardiac catheterization. This way they can see the effect of the medicine on the patient’s heart and lungs. They can also adjust the dose to reduce the side effects that may occur--for example, systemic low blood pressure (hypotension); nausea; angina; headaches; or flushing. To determine whether a drug is improving a patient’s condition, both the pulmonary pressure and the amount of blood being pumped by the heart (the cardiac output) must be evaluated. A decrease in pulmonary pressure alone, for example, does not necessarily mean that the patient is recovering; cardiac output must either increase or remain unchanged. The most desirable response is a decrease in pressure and an increase in cardiac output. Once the patient has reached a stable condition, he or she can go home, returning every few weeks or months to the doctor for follow-up.

18 Primary Pulmonary Hypertension

At present, approximately one-quarter to one-half of patients can be treated with calcium channel blocking drugs given by mouth. By relaxing the smooth muscle in the walls of the heart and blood vessels, these calcium channel blockers improve the ability of the heart to pump blood. A vasodilator, prostacyclin, is helping some severely ill patients who are unresponsive to treatment with calcium channel blockers. The drug, which has been studied in clinical trials, imitates the natural prostacyclin that the body produces on its own to dilate blood vessels. Prostacyclin also seems to help prevent blood clots from forming. Prostacyclin is administered intravenously by a portable, battery-operated pump. The pump is worn attached to a belt around the waist or carried in a small shoulder pack. The medication is then slowly and continuously pumped into the body through a permanent catheter placed in a vein in the neck. Protstacyclin seems to improve pulmonary hypertension and permit more physical activity. It is sometimes used as a bridge to help those patients waiting for a transplant, while in other cases it is used for long-term treatment.

Transplantation The first heart-lung transplant was performed in this country in 1981. Many of these operations were performed for patients with PPH. The survival rate is the same as for other patients with heart-lung transplants, about 60 percent for 1 year, and 37 percent for 5 years. The single lung transplant is the most common method of transplant used in cases of PPH. This procedure, in which one lung--either the left or right--is replaced, was first performed in 1983 in patients with pulmonary fibrosis. Double lung transplants are also done to treat PPH, but are less common than the single lung transplant for treatment of PPH. There are fewer complications with the single lung transplant than with the heart-lung transplant, and the survival rate is on the order of 70 percent for 1 year. A surprising finding is the remarkable ability of the right ventricle to heal itself. In patients with lung transplants, both the structure and function of the right ventricle markedly improve. Complications of transplantation include rejection by the body of the transplanted organ, and infection. Patients take medications for life to reduce their body’s immune system’s ability to reject “foreign” organs.

Guidelines 19

The Primary Pulmonary Hypertension Patient Registry, 19811988 In 1981, the National Heart, Lung, and Blood Institute (NHLBI) established the first PPH-patient registry in the world. The registry followed 194 people with PPH over a period of at least 1 year and, in some cases, for as long as 7.5 years. Much of what we know about the illness today stems from this study. At the time the patients enrolled in the registry, 75 percent were in functional classes 3 or 4. They had an average mean pulmonary artery pressure three times the normal, an abnormally high pressure in the right side of the heart, and a reduced cardiac output. In making the diagnosis of PPH, investigators found no complications arising from cardiac catheterization. The study findings show that pulmonary artery pressure in patients who had symptoms for less than 1 year was similar to that in patients who had symptoms for more than 3 years. Researchers also found that patients whose only symptom was difficulty in breathing upon exercise already had very high pulmonary artery pressure. This suggests that the pulmonary artery pressure rises to high levels early in the course of the disease. No correlations could be found between the cause of PPH and cigarette smoking, occupation, place of residence, pregnancy, use of appetite suppressants, or use of prescription drugs, including oral contraceptives. This study was designed to serve only as a registry, so it was not possible to evaluate the effectiveness of treatment. Because we still do not understand the cause or have a cure for PPH, NHLBI remains committed to supporting basic and clinical studies of this illness. Basic research studies are focusing on the possible involvement of immunologic and genetic factors in the cause and progression of PPH, looking at agents that cause narrowing of the pulmonary blood vessels, and identifying factors that cause growth of smooth muscle and formation of scar tissue in the vessel walls. Most important is finding a reliable way to diagnose PPH early in the course of the disease that does not require cardiac catheterization.

20 Primary Pulmonary Hypertension

Living with Primary Pulmonary Hypertension With the cause of primary pulmonary hypertension still unknown, there is at present no known way to prevent or cure this disease. However, many patients report that by changing some parts of their lifestyle, they can go about many of their daily tasks. For example, they do relaxation exercises, try to reduce stress, and adopt a positive mental attitude. People with PPH go to school, work at home or outside the home part-time or full-time, and raise their children. Indeed, many patients with PPH do not look sick, and some feel perfectly well much of the time as long as they do not strain themselves physically. Walking is good exercise for many patients. Some patients with advanced PPH carry portable oxygen when they go out; patients who find walking too exhausting may use a wheelchair or motorized scooter. Others stay busy with activities that are not of a physical nature. For the patient who lives at a high altitude, a move to a lower altitude-where the air is not so thin, and thus the amount of oxygen is higher--can be helpful. Medical care is important, preferably by a doctor who is a pulmonary vascular specialist. These specialists are usually located at major research centers. PPH patients can also help themselves by following the same sensible health measures that everyone should observe. These include eating a healthy diet, not smoking, and getting plenty of rest. Pregnancy is not advised because it puts an extra load on the heart. Oral contraceptives are not recommended, and other methods of birth control should be used. Most doctors and patients agree that it is important for both patient and family to be as informed as possible about PPH. In this way everyone can understand the illness and apply that information to what is happening. In addition to family and close friends, support groups can help the PPH patient.

For More Information If you have questions on PPH, contact: National Heart, Lung, and Blood Institute Office of the Director, Division of Lung Diseases II Rockledge Centre

Guidelines 21

6701 Rockledge Drive, MSC 7952 Bethesda, MD 20892-7952 (301) 435-0233 For additional copies, write or call: NHLBI Health Information Center P.O. Box 30105 Bethesda, MD 20824-0105 (301) 592-8573 Other information can be obtained from: Pulmonary Hypertension Association (PHA) 850 Sligo Avenue Suite No. 800 Silver Spring, MD 20910 Patient Hotline - 1 (800) 748-7274 www.phassociation.org

More Guideline Sources The guideline above on primary pulmonary hypertension is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to primary pulmonary hypertension. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with primary pulmonary hypertension. 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.

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you

22 Primary Pulmonary Hypertension

can either search using the alphabetical index or browse by broad topic areas. If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on primary pulmonary hypertension and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Primary Pulmonary Hypertension Source: Bethesda, MD: National Heart, Lung, and Blood Institute. 1992. 21 p. Contact: Available from United Patients' Association for Pulmonary Hypertension (UPAPH), Inc. P.O. Box 061556, Palm Bay, FL 32906- 1556. (815) 758-4101 or (800) 748-7274; FAX (201) 358-6823. Price: Free. Summary: This booklet discusses the cause of primary pulmonary hypertension, the course of the disease, its symptoms, diagnosis, and treatment and research into the cause of the disease.

·

Pulmonary Hypertension Source: Danvers, MA: Scleroderma Foundation. 1998. 6 p. Contact: Available from Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield, MA 01922. (800) 722-4673 or (978) 463-5843. Fax (978) 4635809. E-mail: [email protected]. Website: www.scleroderma.org. PRICE: Single copy $1.00.

Guidelines 23

Summary: This pamphlet for people with scleroderma uses a question and answer format to provide information about pulmonary artery hypertension. This type of high blood pressure involves the arteries that take blood from the right side of the heart to the lungs. The pamphlet describes the types of pulmonary artery hypertension that occur in scleroderma, including hypertension with or without scarring of the lung tissue. It also presents the symptoms of pulmonary artery hypertension, highlights the tests that might be conducted to diagnose pulmonary artery hypertension, explains the natural course of this condition in scleroderma, and discusses options for treating this type of hypertension. Pulmonary hypertension not related to scleroderma may be treated with oxygen therapy and anticoagulation therapy. Right-heart failure may be treated with various medications, including calcium channel blockers, diuretics, and an experimental drug known as prostacyclin. In addition, the pamphlet presents the mission of the Scleroderma Foundation.

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 their site located at http://www.guideline.gov by using the keyword “primary pulmonary hypertension” or synonyms. The following was recently posted: ·

AAFP summary of policy recommendations for periodic health examination. (Revision 5.1). Source: American Academy of Family Physicians.; 1996 August (revised 2001 Dec); 15 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2379&sSearch_string=primary+pulmonary+hypertension

·

ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography). Source: American College of Cardiology/American Heart Association/Society for Cardiac Angiography and Interventions.; 1999 May; 70 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1161&sSearch_string=primary+pulmonary+hypertension

24 Primary Pulmonary Hypertension

·

ACC/AHA guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). Source: American College of Cardiology/American Heart Association.; 1997 July (reviewed 2000); 51 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0033&sSearch_string=primary+pulmonary+hypertension

·

ACC/AHA guidelines for the clinical application of echocardiography: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography). Source: American College of Cardiology/American Heart Association.; 1997 March 18 (reviewed 2000); 59 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0032&sSearch_string=primary+pulmonary+hypertension

·

ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Source: American College of Cardiology/American Heart Association.; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2340&sSearch_string=primary+pulmonary+hypertension

·

ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Source: American College of Cardiology/American Heart Association.; 2000; 93 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1800&sSearch_string=primary+pulmonary+hypertension

Guidelines 25

·

ACR Appropriateness Criteria™ for acute chest pain--suspected pulmonary embolism. Source: American College of Radiology.; 1995 (revised 1999); 7 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1607&sSearch_string=primary+pulmonary+hypertension

Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which 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: ·

Primary Pulmonary Hypertension (PPH) Summary: Answers your questions about unexplained elevated blood pressure in the pulmonary artery. This booklet covers the incidence, symptoms, cause, diagnosis, and treatment of the disease. Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=1134

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. 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 primary pulmonary hypertension. 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.

26 Primary Pulmonary Hypertension

Additional Web Sources A number of Web sites that often link to government sites are available to the public. 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

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

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/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Aminorex: An amphetamine-like anorectic agent. It may cause pulmonary hypertension. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Anticoagulants: Agents that prevent blood clotting. Naturally occurring

Guidelines 27

agents in the blood are included only when they are used as drugs. [NIH] Aorta: Blood vessel that delivers oxygen-rich blood from the left ventricle to the body; it is the largest blood vessel in the body. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]

Autopsy: Postmortem examination of the body. [NIH] Bronchitis: Inflammation of one or more bronchi. [EU] Cardiac: Pertaining to the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Catheterization: The employment or passage of a catheter. [EU] Cell: Basic subunit of every living organism; the simplest unit that can exist as an independent living system. [NIH] Chronic: Of long duration; frequently recurring. [NIH] Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

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] Cyanosis: Bluish color of the skin due to insufficient oxygen in the blood. [NIH]

Dexfenfluramine: A serotonin agonist drug used to treat obesity. FDA approval has been withdrawn. [NIH] Dilate: Relax; expand. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dyspnea: Shortness of breath; difficult or labored breathing. [NIH] ECG: Measurement of electrical activity during heartbeats. [NIH] Echocardiography: A test that bounces sound waves off the heart to produce pictures of its internal structures. [NIH] Edema: Abnormal fluid accumulation in body tissues. [NIH] Electrocardiogram:

Measurement of electrical activity during heartbeats.

[NIH]

Embolism: A sudden blocking of an artery by an embolus (clot or a foreign material such as a fat globule) brought to the site by the blood flow. [NIH] Emphysema: Chronic lung disease in which there is permanent destruction of alveoli. [NIH] Endocrinology:

A subspecialty of internal medicine concerned with the

28 Primary Pulmonary Hypertension

metabolism, physiology, and disorders of the endocrine system. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Fenfluramine: A serotonin agonist drug used in the treatment of obesity. FDA approval has been withdrawn. [NIH] Fibrosis: Process by which inflamed tissue becomes scarred. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hypertension: High blood pressure (i.e., abnormally high blood pressure tension involving systolic and/or diastolic levels). The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or taking hypertensive medication. The cause may be adrenal, benign, essential, Goldblatt's, idiopathic, malignant PATE, portal, postpartum, primary, pulmonary, renal or renovascular. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Menopause: The cessation of menstruation in the human female, which begins at about the age of 50. [NIH] Nasal: Pertaining to the nose. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Palpitation: The sensation of rapid heartbeats. [NIH] Perfusion: The passage of fluid through an organ. [NIH] PFT: Pulmonary function test. [NIH] Postmenopausal: Occurring after the menopause. [EU] Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible

Guidelines 29

of induction in all other known elements. [EU] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Spirogram: A record of the amounts of air being moved in and out of the lungs. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Syncope: Fainting; temporary loss of consciousness. [NIH] Systemic: Relating to a process that affects the body generally; in this instance, the way in which blood is supplied through the aorta to all body organs except the lungs. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [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 oxygenrich blood from the left atrium and pumps it to the body through the aorta. [NIH]

Seeking Guidance 31

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with primary pulmonary hypertension. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.10 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with primary pulmonary hypertension. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Primary Pulmonary Hypertension As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.11 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 11 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 10

32 Primary Pulmonary Hypertension

your expectations, and how well you cope with your condition can all influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

American Heart Association Address: American Heart Association National Center, 7272 Greenville Avenue, Dallas, TX 75231-4596 Telephone: (214) 373-6300 Toll-free: (800) 242-8721 Fax: (214) 373-0268 Email: [email protected] Web Site: http://www.americanheart.org Background: The American Heart Association (AHA), a national not-forprofit voluntary health agency funded by private contributions, is dedicated to the reduction of death and disability from cardiovascular diseases including heart diseases and stroke. The Association consists of approximately 2,000 community organizations in all states, the District of Columbia, and Puerto Rico. More than 4 million people volunteer with the Association to fight cardiovascular diseases, the nation's number one cause of death and leading cause of disability. Preventing heart disease and stroke is the first priority of the American Heart Association. In support of this goal, the Association has contributed more than one billion dollars to cardiovascular research since 1949. The Association also distributes a variety of educational materials and sponsors continuing medical education (CME) seminars and meetings.

·

Association for Pulmonary Hypertension Address: P.O.Box 24733 Speedway, IN 46224-0733 Telephone: (800) 748-7274 (toll free); (815) 758-4101 Email: [email protected] Background: The Association for Pulmonary Hypertension (UPAPH) provides fellowship and educational support to families of patients and patients with pulmonary hypertension and primary pulmonary

Seeking Guidance 33

hypertension. The organization makes available current research and findings, information on early detection, lists of resource organizations, information on organ transplantation, and support networks. Publication(s): Pathlight (bi-monthly) Relevant area(s) of interest: books, periodicals, clippings, audio recordings, video; Cardiology; Holdings; Hypertension; Pulmonary hypertension; recordings. ·

Foundation for Pulmonary Hypertension, Inc Address: Foundation for Pulmonary Hypertension, Inc. P.O. Box 61540, New Orleans, LA 70161 Telephone: (504) 533-5888 Fax: (504) 533- 2447 Background: The Foundation for Pulmonary Hypertension is a national not-for-profit research organization that was established in 1984. Pulmonary Hypertension is a condition characterized by abnormally high blood pressure in the arteries that supply the lungs. Pulmonary Hypertension may be an isolated condition that may occur for unknown reasons (Primary Pulmonary Hypertension) or may occur due to or in association with other underlying disorders or conditions (Secondary Pulmonary Hypertension). The mission of the Foundation is to provide 'seed money' for pioneering research into the causes and treatments of Pulmonary Hypertension. The Foundation supports the development of clinical treatments for people with Primary and Secondary Pulmonary Hypertension and informs and educates affected individuals about their conditions. In some cases, the group make appropriate referrals for further evaluation and possible treatment. Educational materials distributed by the Foundation include a regular newsletter and fact sheets. Relevant area(s) of interest: Pulmonary Hypertension

·

March of Dimes Birth Defects Foundation Address: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue, White Plains, NY 10605 Telephone: (914) 428-710 Toll-free: (888) 663-4637 TTY: (914) 997-476 Fax: (914) 997-4763 Email: [email protected] Web Site: http://www.modimes.org

34 Primary Pulmonary Hypertension

Background: The March of Dimes Birth Defects Foundation is a national not-for- profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. Through the Campaign for Healthier Babies, the March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it produces a wide variety of printed informational materials and videos. The March of Dimes public health educational materials provide information encouraging health- enhancing behaviors that lead to a healthy pregnancy and a healthy baby. ·

Pulmonary Hypertension Association Address: Pulmonary Hypertension Association P.O. Box 463, Ambler, PA 19002 Telephone: (215) 591-9016 Toll-free: (800) 748-7274 Fax: (215) 542-5692 Email: [email protected] Web Site: http://www.phassociation.org Background: The Pulmonary Hypertension Association (PHA) is an international not- for-profit voluntary organization that provides educational information and fellowship to people with Primary or Secondary Pulmonary Hypertension. Pulmonary Hypertension is a condition characterized by abnormally high blood pressure in the arteries that supply the lungs. Pulmonary Hypertension may be an isolated condition that may occur for unknown reasons (Primary Pulmonary Hypertension) or may occur due to or in association with other underlying disorders or conditions (Secondary Pulmonary Hypertension). Established in 1992, the organization addresses issues pertinent to people with these disorders such as current research, early detection, orphan drug designations, organ donor awareness, and organ transplantation. The Association's activities include conducting international conferences on Pulmonary Hypertension; providing a networking service to help affected individuals contact one another by phone, through the mail or via the Internet; offering referrals; and publishing a quarterly newsletter entitled 'Pathlight.' The Pulmonary Hypertension Association also offers additional educational and support materials including fact sheets, booklets, and pamphlets. Relevant area(s) of interest: Pulmonary Hypertension

Seeking Guidance 35

·

United Patients Association for Pulmonary Hypertension Address: P.O. Box 24733 Telephone: (800) 748-7274; (815) 758-4101 Fax: (815) 758-4101 Email: [email protected] Background: The United Patients Association for Pulmonary Hypertension (UPAPH) provides fellowship and educational support for members and the public on pulmonary hypertension and primary pulmonary hypertension, including information on current research and findings, early detection, resource organizations, organ transplantation, and support networks. This organization also conducts support group meetings and holds a biennial conference. Publication(s): Pathlight (newsletter, bi-monthly) Relevant area(s) of interest: Holdings; Hypertension; Primary pulmonary hypertension; Pulmonary hypertension; recordings, video recordings.; Reference library, including books, periodicals, clippings, audio

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.

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 primary pulmonary hypertension. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and

36 Primary Pulmonary Hypertension

biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “primary pulmonary hypertension” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

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 “primary pulmonary hypertension”. 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.” By making these selections and typing in “primary pulmonary hypertension” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with primary pulmonary hypertension. You should check back periodically with this database since it is updated every 3 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 specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “primary pulmonary hypertension” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may

Seeking Guidance 37

not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·

PH Central www.phcentral.org

·

The Zena & Michael A. Wiener Cardiovascular Institute www.mssm.edu/cvi/pphtn/support.shtml

·

Maine Medical Center Pulmonary Hypertension Program www.mmc.org/ph/links.html

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with primary pulmonary hypertension must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:12 ·

If you are in a managed care plan, check the plan’s list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a

12

This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

38 Primary Pulmonary Hypertension

training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at http://www.abms.org/newsearch.asp.13 You can also contact the ABMS by phone at 1-866-ASK-ABMS. ·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Doctor14 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about primary pulmonary hypertension?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 14 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 13

Seeking Guidance 39

·

Address the health problem(s) I came with?

·

Ask me my preferences about different kinds of treatments for primary pulmonary hypertension?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor15 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

15

40 Primary Pulmonary Hypertension

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:16 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

16

Seeking Guidance 41

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Alveoli: Tiny sac-like air spaces in the lungs where transfer of carbon dioxide from blood into the lungs and oxygen from air into blood takes place. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]

Cardiovascular: Pertaining to the heart and blood vessels. [EU] Dysplasia: Abnormal development or growth. [NIH] Hypoxia: Too little oxygen available to meet the needs of the body’s tissues. [NIH]

Membrane: Thin, flexible film of proteins and lipids that encloses the contents of a cell; it controls the substances that go into and come out of the cell. Also, a thin layer of tissue that covers the surface or lines the cavity of an organ. [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] Veins: The vessels carrying blood toward the heart. [NIH]

Clinical Trials 43

CHAPTER 3. CLINICAL TRIALS AND PRIMARY PULMONARY HYPERTENSION Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning primary pulmonary hypertension.

What Is a Clinical Trial?17 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for primary pulmonary hypertension is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

17

44 Primary Pulmonary Hypertension

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on primary pulmonary hypertension.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for primary pulmonary hypertension compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment.

How Is a Clinical Trial Conducted? Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on primary pulmonary hypertension carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on primary pulmonary hypertension. In other clinical trials, where a new surgery or

Clinical Trials 45

device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on primary pulmonary hypertension and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how primary pulmonary hypertension develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for primary pulmonary hypertension. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history.

46 Primary Pulmonary Hypertension

If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Primary Pulmonary Hypertension The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to primary pulmonary hypertension.18 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Phase III Randomized Study of UT-15 in Patients with Primary Pulmonary Hypertension Condition(s): Pulmonary Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; United Therapeutics Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of UT15 in patients with severe symptomatic primary pulmonary hypertension. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below

18

These are listed at www.ClinicalTrials.gov.

Clinical Trials 47

Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00004497 ·

Pulmonary Hypertension--Mechanisms and Family Registry Condition(s): Lung Diseases; Hypertension, pulmonary Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To establish a registry of primary pulmonary hypertension (PPH), a lethal disease which causes progressive obstruction of small pulmonary arteries and to investigate basic mechanisms of the disease. Study Type: Registry Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00005357

·

Risk Factors for Pulmonary Hypertension of the Newborn Condition(s): Persistent fetal circulation syndrome; Lung Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a multicenter case-control study of persistent pulmonary hypertension of the newborn (PPHN) in relation to maternal exposure to smoking and non-steroidal anti-inflammatory drugs (NSAIDs). Also, to assess other potential antenatal risk factors and collect and store buccal cell specimens for future analyses. Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00005497

·

Safety and Efficacy of Sitaxsentan in the Treatment of Pulmonary Arterial Hypertension Condition(s): Pulmonary Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): ICOS-Texas Biotechnology; ICOS; Texas Biotechnology Corporation Purpose - Excerpt: This is a clinical research study designed to evaluate an investigational new medication called sitaxsentan for the treatment of pulmonary arterial hypertension (patients with NYHA functional class II, III or IV). The purpose of this study is to evaluate the safety and

48 Primary Pulmonary Hypertension

effectiveness of two different doses of sitaxsentan, compared to placebo (inactive treatment) for the treatment of pulmonary arterial hypertension. Patients who complete this trial may be eligible to take part in an extension trial (Protocol FPH01-X). Eligible patients who receive placebo in the 12-week study cross over to receive sitaxsentan for the extension trial. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00034307 ·

Secondary Pulmonary Hypertension in Adults with Sickle Cell Anemia Condition(s): Pulmonary Hypertension; Sickle Cell Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The purpose of this study is to determine how often people with sickle cell anemia develop pulmonary hypertension-a serious disease in which blood pressure in the artery to the lungs is elevated. Men and women 18 years of age and older with sickle cell anemia may be eligible for this study. Participants will undergo an evaluation at Howard University's Comprehensive Sickle Cell Center in Washington, D.C. or at the National Institutes of Health in Bethesda, Maryland. It will include the following: -medical history -physical examination -blood collection (no more than 50 ml., or about 1/3 cup) to confirm the diagnosis of sickle cell anemia, sickle cell trait or beta-thalassemia (Some blood will be stored for future research testing on sickle cell anemia.) -echocardiogram (ultrasound test of the heart) to check the pumping action of the heart and the rate at which blood travels through the tricuspid valve. Following this evaluation, a study nurse will contact participants twice a month for 2 months and then once every 3 months for the next 3 years for a telephone interview. The interview will include questions about general health and recent health-related events, such as hospitalizations or emergency room visits. Study Type: Observational Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00011648

Clinical Trials 49

·

Epidemiology of Persistent Pulmonary Hypertension of the Newborn SCOR in Lung Biology and Diseases in Infants and Children Condition(s): Lung Diseases; Cardiovascular Diseases; Defect, Congenital Heart; Heart Diseases; Persistent fetal circulation syndrome Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct an epidemiologic study of persistent pulmonary hypertension of the newborn ( PPHN) infant. Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00005323

·

Phase IV Study of Chronic Infusional Epoprostenol for Severe Primary Pulmonary Hypertension Condition(s): Hypertension, Pulmonary Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Baylor College of Medicine Purpose - Excerpt: Objectives: I. Provide epoprostenol (Flolan, prostaglandin I2) by chronic infusion to patients with severe primary pulmonary hypertension for whom no alternative therapy is available. II. Obtain additional safety information on continuous infusion epoprostenol. III. Obtain additional information on economic resource health consumption. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2b/show/NCT00004754

50 Primary Pulmonary Hypertension

Benefits and Risks19 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for primary pulmonary hypertension. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve health or prevent diseases or disorders.

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with primary pulmonary hypertension. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient.

What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f2 91. 19

Clinical Trials 51

receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of you.

·

Know any costs involved for you or your insurance provider.

·

Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

52 Primary Pulmonary Hypertension

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed).

What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don’t have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for primary pulmonary hypertension? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

·

What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will I have to come back for follow-up exams?

·

What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

·

How will my health be monitored?

·

Where will I need to go for the clinical trial? How will I get there?

·

How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

Clinical Trials 53

·

Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?

·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “primary pulmonary hypertension” (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/

·

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

·

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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General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Clinical Trials 55

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Abdominal: Pertaining to the abdomen. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [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 Tlymphocytes, 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] Arterial: Pertaining to an artery or to the arteries. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bronchopulmonary: Pertaining to the lungs and air passages. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cardiopulmonary: Pertaining to the heart and lungs. [EU] 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] EKG: Measurement of electrical activity during heartbeats. [NIH] Enzyme: Substance, made by living cells, that causes specific chemical changes. [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] Hepatitis: Inflammation of the liver. [EU] Infusion: The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU] Lamivudine: A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to

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treat HIV disease. [NIH] Lethal: Deadly, fatal. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Respiratory: Pertaining to respiration. [EU] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]

57

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on primary pulmonary hypertension. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on primary pulmonary hypertension. In Part II, as in Part I, our objective is not to interpret the latest advances on primary pulmonary hypertension or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with primary pulmonary hypertension is suggested.

Studies 59

CHAPTER 4. STUDIES HYPERTENSION

ON

PRIMARY

PULMONARY

Overview Every year, academic studies are published on primary pulmonary hypertension or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on primary pulmonary hypertension. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on primary pulmonary hypertension and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and primary pulmonary hypertension, 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

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“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 in “primary pulmonary hypertension” (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.

Federally-Funded Hypertension

Research

on

Primary

Pulmonary

The U.S. Government supports a variety of research studies relating to primary pulmonary hypertension and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.20 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. Visit the site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to primary pulmonary hypertension and related conditions. 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 primary pulmonary hypertension and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for primary pulmonary hypertension: ·

Project Title: Developmental Regulation of O2 Sensing in the Lung Principal Investigator & Institution: Cornfield, David N.; Pediatrics; University of Minnesota Twin Cities Twin Cities Minneapolis, Mn 55455

20 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Timing: Fiscal Year 2000; Project Start 0-SEP-1999; Project End 1-AUG2003 Summary: At birth, the pulmonary circulation changes dramatically. Pulmonary blood flow increases 8-10 fold while pulmonary arterial (PA) pressure declines. If the pulmonary circulation does not make the transition to a high flow, low pressure circuit, then persistent pulmonary hypertension of the newborn (PPHN) results. PPHN is characterized by increased pulmonary vascular tone and reactivity, resulting in severe central hypoxemia that responds incompletely to the administration of supplemental O2 and other vasodilator stimuli. Neither prevention nor cure is currently available. Treatment options are compromised by incomplete understanding of the mechanisms responsible for postnatal adaptation of the pulmonary circulation. While the acute increase in O2 tension is clearly an essential physiologic stimulus for pulmonary vasodilation in the perinatal period, the identity of the O2 sensor remains unknown. Thus, the mechanism whereby the perinatal pulmonary vasculature senses and vasodilates in response to the acute increase in O2 tension remains incompletely understood. Treatment strategies are compromised by the lack of molecular targets for therapy. This proposal seeks to determine whether the ability of the pulmonary vasculature to respond to an acute increase in O2 tension is developmentally regulated and the subcellular mechanisms that allow the perinatal pulmonary circulation to vasodilate in response to an increase in O2 tension. Evidence suggests that potassium (K+) channels in PA smooth muscle cells (SMC) act as the O2 sensor. Work from our laboratory suggests that the calcium-sensitive K+ (KCa) channel plays a central role in mediating the response of the perinatal pulmonary circulation to an acute increase in O2 tension. We propose the working HYPOTHESIS that oxygen activates a KCa channel through intracellular calcium release to cause PA SMC Em hyperpolarization, contributing to perinatal pulmonary vasodilation. The specific aims are to test the following hypotheses: Aim 1. The KCa channel is a major component of PA SMC O2 sensing in the late-gestation fetus and newborn and is developmentally regulated Aim 2. Activation of the PA SMC KCa channel through Ca2+ sparks contributes to perinatal pulmonary vasodilation. To test these hypotheses, we plan experiments using electrophysiology, dynamic calcium imaging, confocal microscopy, molecular biology, immunocytochemistry, and whole animal physiology. The experiments will provide definitive identification of an O2 sensor in the neonatal pulmonary circulation that may be developmentally regulated and elucidate the subcellular processes that lead to its activation, thereby providing a novel molecular target to address neonatal pulmonary vascular disease.

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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Endothelial Gene Delivery for Pulmonary Hypertension Principal Investigator & Institution: Curiel, David T.; Director; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 1-AUG-2001; Project End 1-JUL2005 Summary: Pulmonary vascular disease constitutes a major cause of mortality, morbidity and healthcare expenditure. Although the underlying causes are mutifactorial, this condition is generally characterized by increased pulmonary vascular resistance, which develops on the basis of both vasoconstriction and arterial vascular remodeling. Within this context, pathobiologic changes in the pulmonary endothelium are understood to playa central role in the development of both of these characteristic disease features. Studies of pathologic material from patients have demonstrated dysregulated expression of factors relevant to vasomotor tone and vascular wall remodeling. It is clear. however, that a fuller understanding of these pulmonary endothelial abnormalities will be required to allow rational interventional strategies. In this regard, methods allowing specific and directed perturbations in gene expression profiles within pulmonary endothelium would potentially provide unique insight into disease pathophysiology. On this basis, it would be desirable to develop technologies to achieve the goal of transient alterations in gene expression patterns selectively within pulmonary endothelium. Such gene-based methods would allow rational analysis of candidate genes with respect to their role in the pathobiology of this condition. Of note, these same methods would potentially allow directed therapeutic interventions. We have recently developed methods to alter the tropism of Ad vectors. These modifications have allowed the achievement of cell-specific gene delivery to pulmonary vascular endothelium in vivo after systemic vascular administration of the vector. We will use these modified Ad vectors to deliver relevant genes to the pulmonary endothelium in rat models of pulmonary hypertension and thrombosis, as a means to discover new insights into the pathophysiology of pulmonary hypertension. In these analyses we will asses the impact of gene delivery on pulmonary vascular pressures, vascular remodeling and thrombosis. In addition, it is our hypothesis that we can further improve the targeting properties of adenoviral vectors by genetic means, thereby improving the efficiency and specificity for I pulmonary endothelial markers and generating agents of potential clinical utility. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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·

Project Title: Genesis of Pulmonary Hypertension Principal Investigator & Institution: Cahill, Barbara C.; Internal Medicine; University of Utah 110 Park Bldg Salt Lake City, Ut 84112 Timing: Fiscal Year 2000; Project Start 1-AUG-1996; Project End 1-JUL2002 Summary: Primary pulmonary hypertension (PPH) is a clinical syndrome encompassing a collection of disorders of the pulmonary vasculature in which pathologic expansion of the mesenchymal compartment obstructs pulmonary blood flow in the absence of any underlying cardiac or pulmonary parenchymal disease. While a small number of patients demonstrate clinical improvement with vasodilator therapy, the majority die within 2 to 5 years of pulmonary circulatory failure. The morphologic and physiologic vascular changes of PPH have been well described, but the specific chain of events and regulatory elements which initiate and perpetuate expansion of the vascular mesenchymal compartment are not known. In studies of ex vivo vascular specimens, animal models of PPH, atherosclerosis, and repair of vascular injury, a defined set of profibrotic growth factors are associated with expansion of the mesenchymal compartment and modulation of vascular tone. Such studies, however, have not been helpful in defining the regulatory elements involved in the genesis of the anatomic changes observed in PPH. We propose to examine one question essential to understanding the genesis of the vascular fibroproliferative response: Can increased local concentrations of a profibrotic ligand which promotes smooth muscle cell and fibroblast migration, proliferation, and matrix deposition within the vascular bed lead to pulmonary hypertension, or is concomitant vascular injury required for pulmonary hypertension to occur? To answer this question we have chosen to utilize a transgenic murine model in which endothelial cells overexpress PDGF-A. To date, a chimeric gene containing a PDGF-A construct under the direction of the von Willebrand factor (VWF) regulatory element has been inserted into the mouse genome. Founder mice incorporating the gene have been identified. Progeny of these transgenic animals will provide a model system with which to examine the role of profibrotic ligands in the genesis of the pulmonary vascular fibroproliferative response. Mice expressing the VWF/PDGF-A gene will be examined for the physiologic and morphologic changes which occur in the pulmonary vascular bed over time and in response to established models of pulmonary vascular injury. Potential therapeutic strategies for patients with PPH hinge on determining whether interdiction of profibrotic ligands can prevent maladaptive vascular fibroproliferation, or whether preventing injury to the vascular bed must be the primary clinical goal. Our objective is to provide experimental evidence to guide

64 Primary Pulmonary Hypertension

in developing therapies for a group of diseases that remains largely refractory to current medical treatment. Working as the primary investigator on this project and the interacting with my co-sponsors will increase my knowledge of vascular biology as it relates to the spectrum of pulmonary vascular disease. My goal with this project is to acquire the skills and knowledge required to become and independent investigator and advance my career as an academic physician. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Hypertension, Risk for Hypertension and Hypoalgesia Principal Investigator & Institution: France, Christopher R.; Psychology; Ohio University Athens Athens, Oh 45701 Timing: Fiscal Year 2000; Project Start 1-MAY-2000; Project End 0-APR2004 Summary: The long-term objective of the proposed research is to evaluate hypoalgesia as a biobehavioral marker of risk for hypertension. The research will test the hypothesis that hypoalgesia and hypertension share a common pathophysiology (i.e., central opioid hyposensitivity) that is characterized by enhanced activation of endogenous opiates and supraspinal pain modulation systems. To the extent that this hypothesis is true, individual differences in nociceptive responses at rest, during opiate blockade, and during supraspinal activation may be used to predict longitudinal changes in blood pressure. The findings from this project may also help to explain the attenuation of clinical pain (e.g., angina) that can complicate early arid accurate detection of heart disease in individuals with hypertension. Three studies are proposed that will use the nociceptive flexion reflex (NFR), defined as the intensity of sural nerve stimulation required to elicit leg withdrawal, as an objective measure of nociception. Study l will determine NFR thresholds in controls and unmedicated patients with newly-diagnosed hypertension, and will assess endogenous opiates and descending pain modulation as mediators of hypertensive hypoalgesia. Study 2 will determine NFR thresholds in young adults at high and low risk for hypertension (defined by parental history of hypertension and resting blood pressure), and will also assess endogenous opiates and descending pain modulation as mediators of hypoalgesia in those at high risk for hypertension. Study 3 will evaluate NFR thresholds at rest and changes in NFR threshold in response to Supraspinal modulation as predictors of longitudinal changes in blood pressure in young adults at high and low risk for hypertension. The proposed studies are important for several reasons. Studies l and 2 will assess promising mechanisms of hypoalgesia which may lead to important insights concerning the role of endogenous opiates

Studies 65

in the pathophysiology of hypertension. Study 3 will evaluate nociceptive responses as a means of identifying those at greatest risk for hypertension among heterogeneous groups of high risk men and women. This information could be used to identify the best candidates for behavioral and other risk reduction efforts. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Inos Gene Transfection in Pulmonary Hypertension Principal Investigator & Institution: Chicoine, Louis G.; Pediatrics; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000; Project Start 1-APR-1999; Project End 1-MAR2004 Summary: Pulmonary hypertension (PH) is a significant cause of morbidity and mortality affecting a broad range of patients. Neonatal pulmonary hypertension is the second leading cause for admission to neonatal intensive care units for respiratory support. In adults, PH causes significant morbidity and mortality in patients with chronic obstructive pulmonary disease. In all patients, PH is characterized by cellular proliferation and altered vasoreactivity in the pulmonary vascular bed. The objectives of this proposal are to evaluate the vasodilator efficacy and toxicity of NO produced by virally mediated inducible nitric oxide synthase (iNOS) gene transfection in the lung and to determine the effect of virally transfected iNOS on the pathogenesis of PH. The general hypothesis is that virally transfected iNOS will result in sufficient NO formation to modulate pulmonary vasoconstriction and attenuate pulmonary vascular changes associated with pulmonary hypertension, but insufficient NO formation to result in toxicity. Utilizing human iNOS gene and, as a control, the E. coli lac Z reporter gene coding for betagalactosidase (beta-gal) adenovirus constructs our goals set forth in this proposal are: 1) to optimize iNOS gene delivery and expression in the rat lung, 2) to determine the role of transfected iNOS on the development of pulmonary hypertension, and 3) to compare intravascular and intratracheal delivery of the iNOS gene in terms of gene expression, vascular reactivity and toxicity. These goals are addressed in the following specific aims: Specific Aim number 1: Assess the effectiveness of adenovirus-mediated iNOS gene transfection in attenuating acute pulmonary vasoconstrictor responses. Specific Aim number 2: Assess iNOS gene transfection-mediated effects on the development of chronic hypoxia-induced pulmonary hypertension. Specific Aim number 3: Assess the efficacy and toxicity of intravascularly and intratracheally administered adenoviral iNOS constructs. The methods will involve using adenovirus constructs containing the gene for iNOS or beta-gal that

66 Primary Pulmonary Hypertension

will be administered intravascularly; the lungs will then be studied to determine vascular reactivity, NO production, and localization of transfected iNOS. Some rats will be transfected and exposed to chronic hypoxia. Finally, intravascular and intratracheal delivery will be compared in terms of gene localization and toxicity. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Nitric Oxide/Cyclic Gmp Cascade in Neonatal Pulmonary Hypertension Principal Investigator & Institution: Abman, Steven H.; ; University of Colorado Hlth Sciences Ctr 4200 E 9Th Ave Denver, Co 80262 Timing: Fiscal Year 2000 Summary: (Adapted from the Applicant's Abstract) Failure of the pulmonary circulation to achieve or sustain the normal decrease in pulmonary vascular resistance (PVR) at birth contributes significantly to the pathophysiology of two major clinical problems of post-natal adaptation: hyaline membrane disease (HMD) and persistent clinical pulmonary hypertension of the newborn (PPHN). Although surfactant therapy is effective in many premature neonates with severe HMD, patients who fail to respond have several disease which is characterized by elevated PVR and high mortality. In PPHN, a clinical syndrome of mostly full-term neonates high PVR causes right-to-left extra-pulmonary shunt and several hypoxemia. Mechanisms underlying pulmonary vascular dysfunction in premature neonates with sever HMD are poorly understood, but reflect the effect of immaturity and the response to acute post-natal lung injury. In contrast, altered pulmonary vascular reactivity and structure in mature neonates with severe PPHN are often due to chronic intrauterine stress. In both diseases, the pulmonary circulation fails to adapt to post-natal life with adequate reduction in PVR, causing profound hypoxemia and poor outcome. Experimental studies suggest that the endogenous nitric oxide (NO)-cGMP cascade (which includes activities of at least 3 enzyme systems: NO synthase (NOS), soluble guanylate cyclase (sGC) AND cGMP-specific (Type V) phosphodiesterase; PDE 5) modulates pulmonary vascular tone and reactivity in utero and contributes to the normal fall in PVR at birth. Since maturational changes in the NO-cGMP cascade occur during fetal life, the effects of premature birth and lung injury on pulmonary vasoreactivity are closely linked with disruption of normal developmental changes in endothelial and smooth muscle function. Whether altered NO-cGMP activity, such as an imbalance between NO5 and PDE5 activities, contribute to high PVR and abnormal vascoreactivity in diseases associated with failure of the pulmonary transition is unknown. In

Studies 67

addition, inhaled NO has successfully treated many neonates with several PPHN, prematures with severe HMD, little is known about its potential toxicity, non-vasodilator effects in the developing lung, mechanisms underlying poor responsiveness in some patients, or possible effects on the endogenous NO-cGMP cascade. To examine mechanisms contributing to abnormalities of the perinatal pulmonary circulation and to better understand inhaled NO therapy, they propose a series of parallel experiments which examines the biochemistry and pathophysiology of the NO-cGMP cascade in the normal developing lung circulation and established models of HMD and PPHN in fetal lambs. These studies will test the hypothesis that: 1) severe prematurity and vascular injury due to acute post-natal lung injury or chronic hypertension in utero alter the pulmonary vascular NO-cGMP cascade, causing abnormal vasoreactivity and sustained elevations of PVR after birth; and 2) strategies which increase lung NO activity, such as inhaled NO therapy, inhibition of PDE5, or both, will lower PVR and improve oxygenation without adverse effects in the developing lung. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: NO/CGMP Relaxation in Pulmonary Hypertension Principal Investigator & Institution: Fouty, Brian W.; Medicine; University of Colorado Hlth Sciences Ctr 4200 E 9Th Ave Denver, Co 80262 Timing: Fiscal Year 2000; Project Start 1-JUL-1996; Project End 0-JUN2002 Summary: (Adapted from the applicant's abstract) Pulmonary hypertension (PHT) represents an important clinical problem in the United States. Increased vascular resistance occurs through the combined mechanisms of increased tone and vessel remodeling. Nitric oxide (NO) is an important endogenous vasodilator currently used clinically in ARDS, primary pulmonary hypertension, and persistent pulmonary hypertension of the newborn. Synthesized in the vascular endothelium, its vasorelaxant effects are thought to be primarily mediated through cGMP-dependent reductions in cytosolic [Ca++] in the vascular smooth muscle. A cGMP-dependent kinase (PKG) is thought to be the central figure in cGMP-induced reductions in [Ca++]I. Much of the evidence to support this PKG-dependent pathway has been determined in smooth muscle cells from conduit pulmonary arteries or from other organs, however, and not from the pulmonary circulation that most of the NO/cGMP-dependent relaxation occurs independently of PKG. In addition to activation of PKG, cGMP can also act on membrane bound ion channels. These recently identified ion channels are nonselective to

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cations and directly bind cGMP and do not require phosphorylation by PKG. The applicants have identified in rat pulmonary microvascular vessels a fragment of this cyclic nucleotide gated (CNG) ion channel using reverse transcriptase/polymerase chain reaction (RT/PCR). The fragment has sequence homology to a cGMP-inhibited ion channel previously identified in the renal epithelium. Given their observation of a cGMP-dependent, but PKG-independent vasorelaxation in the hypertensive pulmonary circulation they hypothesize that this CNG cation channel may be upregulated and activated in PHT. An important component of NO/cGMP dependent vasodilation could involve closure of these channels. This would be consistent with their observations in the hypertensive pulmonary circulation of an increased reliance on NOdependent, but PKG-independent vasorelaxation. In this proposal they intend to determine the importance and mechanism of this PKGindependent pathway in the pulmonary circulation with particular emphasis on the potential role of the CNG cation channel. Genetic and hypoxia-induced rat models of PHT will be studied. To determine the mechanism of NO/cGMP dependent relaxation they will examine the effect of selective NO, cGMP, and PKG inhibitors on pulmonary vascular resistance in isolated perfused lungs and also on changes in [Ca++]I at the level of the microvascular smooth muscle. To determine the potential role of the CNG channel they will look for evidence of increased gene and protein expression in the hypertensive pulmonary circulation using RT/PCR, ribonuclease protection assay, western blots, and photoaffinity assays. To determine the molecular and biophysical characteristics of the channel they plan to express the full length gene in Chinese hamster ovary cells. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Perinatal Pulmonary Hypertension--Developmental Mediator Principal Investigator & Institution: Fineman, Jeffrey R.; Associate Professor; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94143 Timing: Fiscal Year 2000; Project Start 1-JUL-1999; Project End 0-JUN2003 Summary: Pulmonary hypertension and its associated altered vascular reactivity, are a major source of morbidity and mortality for children with congenital heart disease (CHD) and increased pulmonary blood flow. Pulmonary vascular tone is regulated, in part, by a complex interaction of vasoactive substances produced locally by the vascular endothelium, such as nitric oxide (NO) and endothelin-1 (ET-1). Endothelial injury

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secondary to CHD with increased pulmonary blood flow disrupts these regulatory mechanisms, and has been implicated as a potential factor in the development of pulmonary hypertension. To investigate the role of early endothelial dysfunction in the pathophysiology of pulmonary hypertension secondary to CHD, we established a unique model of pulmonary hypertension with increased pulmonary blood flow, utilizing in utero placement of a large aortopulmonary shunt in the fetal lamb. Based on our preliminary data, we hypothesize that increased pulmonary blood flow produces a progressive increase in ET-mediated vasoconstriction and mitogenesis that is initially opposed by an activated NO cascade. However, with further endothelial dysfunction secondary to increased flow and pressure, the NO cascade is decreased. This leads to unopposed ET-mediated vasoconstriction and mitogenesis and the progressive development of pulmonary hypertension and vascular remodeling. In this application, we will utilize our unique animal model, and a sequential and integrated physiologic, biochemical, molecular, and anatomic approach, to investigate this hypothesis. Specifically, we will examine: (a) the normal maturational changes in the NO and ET-1 cascades during the first two months of life; (b) the role of early alterations in the NO and ET-1 cascades in the development of pulmonary hypertension secondary to increased pulmonary blood flow; and (c) the interactions between the NO and ET-1 cascades, and their regulatory mechanisms, in the normal and abnormal pulmonary vasculature. Correlations between endothelial dysfunction, increased vascular reactivity, and vascular remodeling will be made, and predictors of increased vascular reactivity will be sought. This information may improve our ability to recognize early pulmonary vascular changes, and better predict those patients with CHD who will suffer increased periand post-operative morbidity secondary to increased vascular reactivity. This would profoundly affect the timing and feasibility of surgical correction, and should lead to improved treatments and prevention strategies for pulmonary hypertension. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Perinatal Regulation of the Endothelial NOS Gene Principal Investigator & Institution: Black, Stephen M.; Associate Professor; Pediatrics; Northwestern University 303 E Chicago Ave Chicago, Il 60611 Timing: Fiscal Year 2000; Project Start 1-APR-1998; Project End 1-MAR2002 Summary: At birth, ventilation and oxygenation immediately produce a dramatic decrease in pulmonary vascular resistance and an increase in

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pulmonary blood flow with more gradual changes occurring over the next several hours. Nitric oxide (NO), produced from L-arginine by endothelial nitric oxide synthase (eNOS), appears to mediate, at least in part, these gradual changes. Aberrations in NO activity have also been implicated in the pathophysiology of disease states such as persistent pulmonary hypertension of the newborn (PPHN). The mechanism producing the increased NO activity at birth remains unknown. Our overall goals are to determine the factors that regulate pulmonary blood flow and pulmonary vascular resistance at the fetal to newborn transition. The increases in pulmonary blood flow occurring at birth will likely produce an increase in the shear forces on the pulmonary vascular endothelium. NO production, NOS activity, eNOS mRNA and protein expression are increased when endothelial cells (ECS) are exposed to increased shear stress. We hypothesize that the increased shear forces to which the pulmonary system is exposed to after birth will produce an increase in eNOS gene expression; subsequently, this leads to the gradual decrease in PVR and the increased PBF seen in the first several hours after birth. To allow a molecular analysis of the effects of birth on the fetal pulmonary endothelium we have isolated and cultured the relevant late gestation ovine pulmonary arterial ECs. To mimic the effects of increased blood flow we have built a cone-plate viscometer which allows us to expose the EC monolayer to a controlled level of shear stress. We have also cloned the promoter region of the human eNOS gene upstream of a Luciferase reporter. We will use this to identify the DNA sequences within the eNOS promoter (cis-elements) that are activated by shear stress in fetal pulmonary arterial ECs. This may eventually lead to the identification of transcription (transacting) factors responsible for the increase in eNOS gene expression during the transition from fetal to neonatal life. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: PKC Signaling in Camp-Induced Pulmonary Vasodilation Principal Investigator & Institution: Barman, Scott A.; Pharmacology and Toxicology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 1-JUL-2001; Project End 1-MAY2005 Summary: (provided by applicant): Primary Pulmonary Hypertension (PPH) is a disease of unknown origin that results in narrowing Of the pulmonary vasculature causing high pulmonary blood pressure often leading to heart failure. Currently there is little knowledge on the cellular and molecular foundation of PPH. Normally, signaling mechanisms which elevate cAMP and cGMP in the pulmonary vasculature allow for

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the maintenance of a low pressure, high perfusion environment. It is well documented that the activation of the large-conductance, calcium-and voltage-activated potassium (BKca) channel is of primary importance in the regulation of pulmonary arterial pressure and inhibition of the BKca channel has been implicated in the development of pulmonary hypertension. Preliminary data from patch-clamp studies in pulmonary arterial smooth muscle cells (PASM) of the fawn-hooded rat (FHR), a recognized animal model of pulmonary hypertension, suggests that cAMP, an activator of cAMP-dependent protein kinase (PKA), opens the BKca channel through "cross-activation" of the cGMP-dependent protein kinase (PKG). In contrast, protein kinase C (PKC) which causes pulmonary vasoconstriction, inhibits the BKca channel in FHR PASM, but activates the BKca channel in Sprague-Dawley (control) rats. Therefore, the hypothesis of the proposed studies is that cAMPdependent vasodilators relax pulmonary arteries by opening BKca channels in pulmonary arterial smooth muscle by stimulating the activity of PKG, an effect inhibited by activation of PKC in FHR. This hypothesis will be tested by employing state-of-the-art techniques of electrophysiology, vascular contraction, and biochemistry/molecular biology to determine: 1) the effect of cAMP-dependent vasodilators on pulmonary arteries in vitro, 2) the effect of cAMP-elevating agents on whole-cell and single channel K+ currents from single myocytes isolated from pulmonary arteries, 3) cAMP-dependent "cross-activation" of PKG, and 4) the role of PKC on BKca channel activity and whether there is a direct interaction between PKG and PKC on BKca channel modulation. The long term goal of the proposed study is to understand how cAMPelevating agents cause pulmonary arterial vasodilation by an endothelium-independent mechanism. It is believed that these studies will lead to the development of novel therapeutic agents that will help reduce the morbidity and mortality associated with PPH and other pulmonary vascular diseases. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Prostacyclin Synthase and Prostacyclin Receptor in PH Principal Investigator & Institution: Geraci, Mark W.; Associate Professor; University of Colorado Hlth Sciences Ctr 4200 E 9Th Ave Denver, Co 80262 Timing: Fiscal Year 2001; Project Start 7-SEP-2001; Project End 1-JUL-2006 Summary: (provided by applicant) Severe pulmonary hypertension, including primary pulmonary hypertension (PPH), is an important clinical problem with few clinical treatment options. The chronic, intravenous infusion of prostacyclin (PGI2) has been established as the

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treatment of choice for patients with PPH. It is now clear that long-term benefits occur which obviate the need for transplant in many cases. The physiological effects of prostacyclin on platelet behavior, vascular tone control, and cell proliferation are well established; however, we do not know whether prostacyclin effects the vascular remodeling in chronic pulmonary hypertension. Our overall hypothesis is that prostacyclin, through membrane-receptor dependent and independent mechanisms, is an important modulator of pulmonary vascular remodeling. We have demonstrated loss of the prostacyclin receptor (PGIR) protein in the smooth muscle cells of precapillary resistance arteries in patients with PPH. We postulate that impairment of the prostacyclin signal transduction contributes to pulmonary vascular remodeling. We have generated transgenic animals with selective pulmonary prostacyclin synthase (PGIS) overexpression. These animals are protected from the development of hypoxic pulmonary hypertension, and show no acute vasoconstriction or chronic vascular remodeling. In contrast, PGIR knockout (KO) mice, in response to hypoxia, develop rapid pulmonary hypertension accompanied by vascular remodeling. Microarray analysis of the lungs from the transgenic animals demonstrates a change in the global pattern of gene expression, which may be responsible for the "protected" phenotype, including changes in PPARs and COX-2. Our underlying concept is that PGI2 exhibits both membrane-receptor mediated and nuclear-receptor-mediated actions. These alternative mechanisms could include direct effects on gene expression, signaling pathways not yet recognized, or changes in the level of other eicosanoids. Our goal is to examine, using both animal models and cell systems, the effects of PGIS and PGIR on vascular smooth muscle cell (VSMO) growth and differentiation. In Specific Aim 1, we will determine whether pulmonary vascular tone and remodeling are mediated through the PGI2 receptor using bitransgenic mice with PGIS overexpression, but lacking PGIR. Specific Aim 2 is designed to define the effect of PGIS and PGIR on the growth and remodeling of vascular smooth muscle cells. The results of this work are designed to elucidate new potential therapeutic targets for treating pulmonary hypertension, and broaden our understanding of vascular pathology in general. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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E-Journals: PubMed Central21 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).22 Access to this growing archive of e-journals is free and unrestricted.23 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “primary pulmonary hypertension” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for primary pulmonary hypertension in the PubMed Central database: ·

Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis by Saadia Eddahibi and Serge Adnot; 2002 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=64820

·

Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension by Mark De Caestecker and Barbara Meyrick; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59576

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. 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 the public.24 If the publisher has a Web site that Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 22 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. 23 The value of PubMed Central, in addition to its role as an archive, lies 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. 24 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. 21

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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 primary pulmonary hypertension, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “primary pulmonary hypertension” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “primary pulmonary hypertension” (hyperlinks lead to article summaries): ·

High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. Author(s): Rich S, Kaufmann E. Source: Journal of the American College of Cardiology. 1991 November 1; 18(5): 1323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1918710&dopt=Abstract

·

High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Author(s): Rich S, Brundage BH. Source: Circulation. 1987 July; 76(1): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2954725&dopt=Abstract

Vocabulary Builder Accommodation: distances. [EU]

Adjustment, especially that of the eye for various

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] Anorexiant: A drug, process, or event that leads to anorexia. [NIH] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins,

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etc. [EU] Arginine: An essential amino acid that is physiologically active in the Lform. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] CHD: 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] Concomitant: Accompanying; accessory; joined with another. [EU] Contractility: stimulus. [EU]

Capacity for becoming short in response to a suitable

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] 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] Endogenous: Developing or originating within the organisms or arising from causes within the organism. [EU] Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels, and the serous cavities of the body, originating from the mesoderm. [EU] Epithelium: The covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells. [EU] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU]

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Fluoxetine: An antidepressant drug used to promote weight loss whose action is mediated by highly specific inhibition of serotonin reuptake into presynaptic neurons. Serotonin acts in the brain to alter feeding and satiety by decreasing carbohydrate intake, resulting in weight reduction. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [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 beta-synthase and is a risk factor for coronary vascular disease. [NIH] Hyperplasia: The abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue. [EU] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Hypoxemia: Too little oxygen in the blood. [NIH] Idiopathic: Results from an unknown cause. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunization: Protection from disease by administering vaccines that induce the body to form antibodies against infectious agents. [NIH]

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Inhalation: The drawing of air or other substances into the lungs. [EU] 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 insulindependent diabetes mellitus. [NIH] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Ovary: Either of the paired glands in the female that produce the female

78 Primary Pulmonary Hypertension

germ cells and secrete some of the female sex hormones. [NIH] Oxygenation: To provide with oxygen. [NIH] Parvovirus: A genus of the family parvoviridae, subfamily parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be nonpathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH] Pathologic: 1. indicative of or caused by a morbid condition. 2. pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The entire physical, biochemical, and physiological makeup of an individual as determined by his or her genes and by the environment in the broad sense. [NIH] Phentermine: An adrenergic isomeric with amphetamine, used as an anorexic; administered orally as a complex with an ion-exchange resin to produce a sustained action. [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] Physiologic: Normal; not pathologic; characteristic of or conforming to the normal functioning or state of the body or a tissue or organ; physiological. [EU]

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]

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Prophylaxis: The prevention of disease; preventive treatment. [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Refractory: Not readily yielding to treatment. [EU] Renin: An enzyme of the hydrolase class that catalyses cleavage of the leucine-leucine bond in angiotensin to generate angiotensin. 1. The enzyme is synthesized as inactive prorenin in the kidney and released into the blood in the active form in response to various metabolic stimuli. Not to be confused with rennin (chymosin). [EU] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Shunt: 1. to turn to one side; to divert; to bypass. 2. a passage or anastomosis between two natural channels, especially between blood vessels. Such structures may be formed physiologically (e.g. to bypass a thrombosis) or they may be structural anomalies. 3. a surgically created anastomosis; also, the operation of forming a shunt. [EU] 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] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH] Surgical: Of, pertaining to, or correctable by surgery. [EU]

80 Primary Pulmonary Hypertension

Thrombosis: The formation, development, or presence of a thrombus. [EU] 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]

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] Toxoplasma: A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. [NIH]

Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: The diminution of the calibre of vessels, especially constriction of arterioles leading to decreased blood flow to a part. [EU] 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] Ventilation: The process of exchange of air between the lungs and the atmosphere leading to exchange of gases in the blood. [NIH] Ventricular: Pertaining to a ventricle. [EU] 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 substancespecific 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]

Books 81

CHAPTER 5. BOOKS HYPERTENSION

ON

PRIMARY

PULMONARY

Overview This chapter provides bibliographic book references relating to primary pulmonary hypertension. You have many options to locate books on primary pulmonary hypertension. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on primary pulmonary hypertension include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ).

82 Primary Pulmonary Hypertension

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “primary pulmonary hypertension” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:25 ·

Abnormal pulmonary circulation. Author: edited by Edward H. Bergofsky; Year: 1986; New York: Churchill Livingstone, 1986; ISBN: 0443083193 http://www.amazon.com/exec/obidos/ASIN/0443083193/icongroupin terna

·

Crotalaria spectabilis, the pulmonary hypertension plant, by J. M. Kay and Donald Heath. Author: Kay, John Michael; Year: 1969; Springfield, Ill., Thomas [c1969]

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Diagnosis and treatment of pulmonary hypertension. Author: edited by E. Kenneth Weir, Stephen L. Archer, John T. Reeves; Year: 1992; Mount Kisco, NY: Futura Pub. Co., c1992; ISBN: 0879935162 http://www.amazon.com/exec/obidos/ASIN/0879935162/icongroupin terna

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Dispensing with the truth: the victims, the drug companies, and the dramatic story behind the battle over Fen-Phen. Author: Alicia Mundy; Year: 2001; New York: St. Martin's Press, 2001; ISBN: 0312253249 http://www.amazon.com/exec/obidos/ASIN/0312253249/icongroupin terna

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Early pathogenesis of primary hypertension: selected reviews presented at the International Symposium on Primary Hypertension, Implications for Detection and Intervention in Childhood, Rotterdam, 9-10 September 1986. Author: editors, A. Hofman, D.E. Grobbee, an;

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

25

Books 83

Year: 1987; Amsterdam; New York: Excerpta Medica; New York, NY, USA: Sole distributors for the USA and Canada, Elsevier Science Pub. Co., 1987; ISBN: 0444809384 (U.S.) http://www.amazon.com/exec/obidos/ASIN/0444809384/icongroupin terna ·

Experimental production of pulmonary hypertension. Author: Barnes, William Henry, 1926-; Year: 1957; [Minneapolis] 1957

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Experimental production of pulmonary vascular obstructive disease in the newborn calf. Author: Peter Michael Sanfelippo; Year: 1976; [Minneapolis?: s.n.], 1976

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Heart in hypertension. Author: Eddy Noresson; Year: 1979; Goteberg, Sweden: Univ. of Goteberg, Dept. of Physiology, 1979; ISBN: 9172222603

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Intermittent hypoxia and cardiopulmonary system. Author: Bohuslav Ostádal, Jirí Widimský and coll., coworkers, Dagmar Urbanová ... [et al.]; Year: 1985; Praha: Academia, nakl. Ceskoslovenské akademie ved, 1985

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Pathology of pulmonary hypertension. Author: C. A. Wagenvoort and Noeke Wagenvoort; Year: 1977; New York: Wiley, c1977; ISBN: 0471913553 http://www.amazon.com/exec/obidos/ASIN/0471913553/icongroupin terna

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Pediatric Cardiology Workshop: Pulmonary Hypertension, September 22-24, 1985. Author: Division of Heart and Vascular Diseases [and] Division of Lung Diseases, National Heart, Lung, and Blood Institute; Year: 1987; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, [1987]

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Primary pulmonary hypertension. Author: edited by Lewis J. Rubin, Stuart Rich; Year: 1997; New York: M. Dekker, c1997; ISBN: 0824795059 (hardcover: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0824795059/icongroupin terna

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Primary pulmonary hypertension. Author: Walcott, George, 1932-; Year: 1967; [Minneapolis] 1967

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Primary pulmonary hypertension; report on a WHO meeting, Geneva, 15-17 October 1973. Edited by Shuichi Hatano and Toma Strasser. Author: WHO Meeting on Primary Pulmonary Hypertension (1973: Geneva); Year: 1975; Geneva, World Health Organization, 1975; ISBN: 9241560444 http://www.amazon.com/exec/obidos/ASIN/9241560444/icongroupin terna

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Pulmonary blood vessels in lung disease. Author: International Symposium on Pulmonary Circulation V, Prague, July 5-7, 1989; volume

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editors, J. Widimský, J. Herget; Year: 1990; Basel; New York: Karger, 1990; ISBN: 380555155X http://www.amazon.com/exec/obidos/ASIN/380555155X/icongroupi nterna ·

Pulmonary circulation: advances and controversies. Author: editors, C.A. Wagenvoort and H. Denolin; Year: 1989; Amsterdam; New York: Elsevier, 1989; ISBN: 0444810722 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0444810722/icongroupin terna

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Pulmonary circulation: normal and abnormal: mechanisms, management, and the national registry. Author: Alfred P. Fishman, editor; Year: 1990; Philadelphia: University of Pennsylvania Press, 1990; ISBN: 0812281101 http://www.amazon.com/exec/obidos/ASIN/0812281101/icongroupin terna

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Pulmonary hypertension: pathophysiology, diagnosis, treatment, and development of a pulmonary-selective therapy. Author: [Horst Olschewski, Werner Seeger]; Year: 2002; Bremen, Germany: Uni-Med, c2002; ISBN: 3895995940 (hd.)

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Pulmonary hypertension: proceedings of the International Symposium on Pulmonary Circulation II, Prague, June 17-19, 1974. Author: editor: J. Widimský; Year: 1975; Basel; New York: Karger, 1975; ISBN: 3805521715 http://www.amazon.com/exec/obidos/ASIN/3805521715/icongroupin terna

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Pulmonary hypertension and pulmonary vascular disease. Author: [edited by] Norbert F. Voelkel; Year: 1985; New York: Thieme, c1985

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Pulmonary hypertension in tuberculosis of the lungs; a clinical study in advanced cases examined with cardiac catheterization and temporary unilateral occlusion of the pulmonary artery. Author: Uggla, Lars Gustaf; Year: 1957; [Stockholm, 1957]

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Pulmonary hypertension. Author: edited by E. Kenneth Weir and John T. Reeves; Year: 1984; Mount Kisco, N.Y.: Futura Pub. Co., 1984; ISBN: 0879932066 http://www.amazon.com/exec/obidos/ASIN/0879932066/icongroupin terna

·

Pulmonary hypertension. Author: Joseph S. Alpert, Richard S. Irwin, James E. Dalen; Year: 1981; Chicago; London: Year Book Medical Publishers, 1981; ISBN: 0815199155 http://www.amazon.com/exec/obidos/ASIN/0815199155/icongroupin terna

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Pulmonary hypertension. Author: Kaump, Donald Hunter, 1907-; Year: 1936; [Minneapolis, Minn.] 1936

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Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension: assessment report. Author: Olschewski, Horst; Year: 2001; Canberra, ACT: Medicare Services Advisory Committee, Dept. of Health and Aged Care, c2001; ISBN: 0642503419

·

Pulmonary vascular physiology and pathophysiology. Author: edited by E. Kenneth Weir, John T. Reeves; Year: 1989; New York: Dekker, c1989; ISBN: 082477972X (alk. paper) http://www.amazon.com/exec/obidos/ASIN/082477972X/icongroupi nterna

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Pulmonary vascular reactivity. Author: guest editor, E. Kenneth Weir; Year: 1985; [Park Ridge, Ill., U.S.A.]: American College of Chest Physicians, [c1985]

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Pulmonary vascular remodelling. Author: edited by Jill E. Bishop, John T. Reeves, Geoffrey J. Laurent; Year: 1995; London: Portland Press; Brookfield, VT: Ashgate Pub. Co. [distributor], c1995; ISBN: 1855780410 http://www.amazon.com/exec/obidos/ASIN/1855780410/icongroupin terna

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Studies on pulmonary hypertension; observations in a heart catheterization material. Author: Trell, Erik; Year: 1972; [Stockhom, 1972]

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Technology report: nitric oxide therapy. Author: [author, Elizabeth Young]; Year: 1996; Oak Brook, IL: UHC Clinical Practice Adancement Center, c1996

Chapters on Primary Pulmonary Hypertension Frequently, primary pulmonary hypertension will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with primary pulmonary hypertension, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and primary pulmonary hypertension using the “Detailed Search” option. Go directly 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.” By making these selections and typing in “primary pulmonary hypertension” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The

86 Primary Pulmonary Hypertension

following is a typical result when searching for book chapters on primary pulmonary hypertension: ·

Organ Involvement: Pulmonary Source: in Clements, P.J.; Furst, D.E., Eds. Systemic Sclerosis. Baltimore, MD: Williams and Wilkins. 1996. p. 299-331. Contact: Available from Williams and Wilkins, Special Sales Department. (800) 358-3583. Summary: This chapter for health professionals focuses on the clinical manifestations of pulmonary involvement in systemic sclerosis (SSc). SSc produces fibrosing alveolitis or primary pulmonary vascular disease within the lungs. The pathogenesis of these two patterns of abnormality within the lungs of SSc patients is explained. Common pathological findings in fibrosis and pulmonary vascular disease are described. The clinical features of pulmonary disease in SSc are presented, focusing on the features of fibrosing alveolitis and pulmonary arterial hypertension. Other pulmonary complications are highlighted. The prognosis of lung disease in SSc patients is discussed. Methods of assessing pulmonary involvement in SSc are described, including blood tests, radiographic techniques, radionuclide imaging, lung function tests, bronchoalveolar lavage, lung biopsy, and pulmonary vascular investigations. Methods of treating pulmonary SSc are reviewed. 203 references, 7 figures, and 5 tables.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to primary pulmonary hypertension have been published that consolidate information across various sources. These too might be useful in gaining access to additional guidance on primary pulmonary hypertension. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:26 You will need to limit your search to “Directories” and primary pulmonary hypertension using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by”. For publication date, select “All Years”, select language and the format option “Directory”. By making these selections and typing in “primary pulmonary hypertension” (or synonyms) into the “For these words:” box, you will only receive results on directories dealing with primary pulmonary hypertension. You should check back periodically with this database as it is updated every three months.

26

Books 87

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Physicians Experienced with Treating PPH Patients Source: Palm Bay, FL: United Patients' Association for Pulmonary Hypertension, Inc. (UPAPH) 1995. 6p. Contact: Available from United Patients' Association for Pulmonary Hypertension, Inc. (UPAPH). P.O. Box 061556, Palm Bay, FL 32906- 1556. (815) 758-4101 or (800) 748-7274; FAX (201) 358-6823. Price: Free. Summary: This is a listing of physicians who are experienced with treating primary pulmonary hypertension cases.

General Home References In addition to references for primary pulmonary hypertension, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Anatomica : The Complete Home Medical Reference by Peter Forrestal (Editor); Hardcover (2000), Book Sales; ISBN: 1740480309; http://www.amazon.com/exec/obidos/ASIN/1740480309/icongroupinterna · The Breathing Disorders Sourcebook by Francis V. Adams, M.D.; Paperback - 240 pages (November 1998), McGraw Hill - NTC; ISBN: 073730006X; http://www.amazon.com/exec/obidos/ASIN/073730006X/icongroupinterna

· The HarperCollins Illustrated Medical Dictionary : The Complete Home Medical Dictionary by Ida G. Dox, et al; Paperback - 656 pages 4th edition (2001), Harper Resource; ISBN: 0062736469; http://www.amazon.com/exec/obidos/ASIN/0062736469/icongroupinterna · The Merck Manual of Medical Information: Home Edition (Merck Manual of Medical Information Home Edition (Trade Paper) by Robert Berkow (Editor), Mark H. Beers, M.D. (Editor); Paperback - 1536 pages (2000), Pocket Books; ISBN: 0671027263; http://www.amazon.com/exec/obidos/ASIN/0671027263/icongroupinterna · Stedman’s Cardiovascular & Pulmonary Words: Includes Respiratory; Paperback - 888 pages, 3rd edition (June 15, 2001), Lippincott, Williams & Wilkins Publishers; ISBN: 0781730562; http://www.amazon.com/exec/obidos/ASIN/0781730562/icongroupinterna

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Vocabulary Builder Alveolitis: Inflammation of the alveoli. [NIH] Lavage: To wash the interior of a body organ. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH]

Multimedia 89

CHAPTER 6. MULTIMEDIA ON PRIMARY PULMONARY HYPERTENSION Overview Information on primary pulmonary hypertension can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on primary pulmonary hypertension. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Bibliography: Multimedia on Primary Pulmonary Hypertension The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in primary pulmonary hypertension (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on primary pulmonary hypertension. For more information, follow the hyperlink indicated:

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Acquired vascular disease. Source: Grover M. Hutchins; Year: 1972; Format: Slide; [New York]: Medcom, c1972

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Adrenal origin hyypertension [videorecording]. Source: Health Communications Network, Division of Continuing Education, Medical University of South Carolina, in cooperation with Department of Medicine, Division of Nephrology; Year: 1978; Format: I. e. hypertension; [Charleston, S. C.]: The Network, 1978]

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Aldosterone: story of a hormone. Source: by G. D. Searle & Co.; [produced by] Medcom Learning Systems; Year: 1969; Format: Motion picture; [Chicago]: Searle; [Atlanta: for loan by National Medical Audiovisual Center, c1969]

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Atlas of peripheral lung tumors. Source: American Society of Clinical Pathologists, Commission on Continuing Education; Year: 1969; Format: Slide; Chicago: The Society, c1969

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Chest in the neonate. Source: Radiological Society of North America; Year: 1990; Format: Videorecording; Oak Brook, Ill.: The Society, c1990

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Chronic bronchitis and pulmonary emphysema: the application of physical medicine and rehabilitation, part I. Source: Public Health Service, Division of Chronic Diseases and New York University Medical Center, Institute of Physical Medicine and; Year: 1965; Format: Motion picture; [Washington]: The Service; [Atlanta: for loan by National Medical Audiovisual Center, 1965]

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Chronic pulmonary diseases. Source: S. Donald Greenberg and Daniel E. Jenkins; Year: 1971; Format: Slide; New York: Medcom, c1971

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Congenital cardiovascular disease. Source: Averill A. Liebow; Year: 1974; Format: Slide; [Poway, Calif.: Cal-Med Photo, 1974?]

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Cor pulmonale. Source: ACCEL Program and Heart House Learning Center, in conjunction with Stuart Pharmaceuticals; produced by MediCine, ltd; Year: 1978; Format: Slide; [London]: Medi-Cine; [Bethesda, Md.: for sale by American College of Cardiology], c1978

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Cost-effective management of arterial hypertension. Source: the Cleveland Clinic Foundation; Year: 1995; Format: Videorecording; Cleveland, OH: Cleveland Clinic Foundation, c1995

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Diabetes : practical approaches to primary care. Source: a co-production of Multimedia Communications and Physician Education and Development; Year: 2001; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c2001

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Echocardiography slide set. Source: Louis Evan Teichholz; Year: 1974; Format: Slide; [Tarpon Springs, Fla.: Tampa Tracings, 1974]

Multimedia 91

·

Evaluation of cyanosis in the newborn. Source: P. Syamasundar Rao, Max D. Miller, William B. Strong; produced by the Dept. of Pediatrics, Medical College of Georgia, in cooperation with the National Medical Audiovisual Center; Year: 1978; Format: Slide; Atlanta: The Center 1978

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Examination of the cardiac chambers. Source: Georgia Regional Medical Television Network; Year: 1972; Format: Videorecording; [Atlanta: The Network: for loan or sale by Calhoun (A. W.) Medical Library, 1972]

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Hypertension: the challenge of diagnosis. Source: American Heart Association; [made by] Harvest Films; Year: 1968; Format: Motion picture; [New York]: The Association, c1968

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Hypertension in primary care. Source: developed by Academia Medica; Year: 1997; Format: Electronic resource; Stamford, CT: Appleton & Lange New Media, c1997

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Nitric oxide therapy for persistent pulmonary hypertension of the newborn. Source: Children's Hospital, Boston; Year: 1994; Format: Videorecording; Boynton Beach, FL: Distributed by Universal Health Communications, [1994]

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Plain film approach to pulmonary venous obstruction. Source: American College of Radiology Audio-visual Committee on Continuing Education; Year: 1976; Format: Videorecording; [Chicago]: The College, c1976

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Primary hypertension in children. Source: produced by UT/TV; Year: 1993; Format: Videorecording; [Houston, Tex.: UT/TV], c1993

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Primary prevention of hypertension. Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1993; Format: Videorecording; Marshfield, WI: The Clinic, [1993]

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Primary pulmonary hypertension : diagnosis and treatment. Source: Biomedical Media Production Unit, the University of Michigan Medical Center, Office of Educational Resources & Research; Year: 1982; Format: Videorecording; Ann Arbor, Mich.: The University, c1982

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Primary pulmonary hypertension. Source: presented by the Department of Medicine, Emory University, School of Medicine [and] the Emory Medical Television Network; Year: 1988; Format: Videorecording; Atlanta, Ga.: The University, 1988

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Primary pulmonary hypertension. Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983

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Primary sarcoma of the main pulmonary artery : pulmonary artery reconstruction and pneumonectomy. Source: from the Film Library and the Clinical Congress of ACS, Mount Sinai School of Medicine of the City

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University of New York, the Mount Sinai; Year: 1996; Format: Videorecording; Woodbury, CT: Ciné-Med, [1996] ·

Pulmonary hypertension : evolving concepts and mgt.; Pregnancy and heart disease. Source: Mayo Cardiovascular Division; a production of Mayo Audiovisual/Video Communications for the Mayo Clinic Cardiovascular Division; Year: 1998; Format: Videorecording; Rochester, Minn.: Mayo Foundation for Medical Education and Research, c1998

·

Rational approach to newly discovered hypertension. Source: University of Michigan, Medical Center, Department of Postgraduate Medicine and Health Professions Education, Independent Study Unit; Year: 1974; Format: Slide; Ann Arbor: The University: [for loan or sale by its Medical Center, Media Library], c1974

·

Respiratory emergencies. Source: Mosby; Year: 1997; Format: Videorecording; St. Louis, Mo.: Mosby-Year Book, c1997

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Thromboemboli, cor pulmonale, & lung infections. Source: S. Donald Greenberg; produced by Audiovisual Medical Marketing; Year: 1979; Format: Slide; Park Ridge, Ill.: American College of Chest Physicians; [New York: for loan and sale by Audiovisual Medical Marketing], c1979

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Tricuspid regurgitation. Source: a production of Bio-Communications Laboratory, Texas Heart Institute; Year: 1988; Format: Videorecording; Houston, Tex.: The Lab, c1988

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Tuberculosis and the primary care physician. Source: Biomedical Media Production Unit, University of Michigan Medical Center, Office of Educational Resources & Research; Year: 1980; Format: Videorecording; Ann Arbor, Mich.: The University, c1980

Vocabulary Builder Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas are often highly malignant. [EU]

Periodicals and News 93

CHAPTER 7. PERIODICALS AND NEWS ON PRIMARY PULMONARY HYPERTENSION Overview Keeping up on the news relating to primary pulmonary hypertension can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on primary pulmonary hypertension. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover primary pulmonary hypertension beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on primary pulmonary hypertension is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. 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.

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PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “primary pulmonary hypertension” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to primary pulmonary hypertension. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “primary pulmonary hypertension” (or synonyms). The following was recently listed in this archive for primary pulmonary hypertension: ·

Epoprostenol, inhaled iloprost promising for treatment of pulmonary hypertension Source: Reuters Medical News Date: March 21, 2000 http://www.reuters.gov/archive/2000/03/21/professional/links/20000 321clin001.html

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Fenfluramine use linked to increased risk of primary pulmonary hypertension Source: Reuters Medical News Date: March 13, 2000 http://www.reuters.gov/archive/2000/03/13/professional/links/20000 313epid002.html

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Epoprostenol shows promise for treatment of pulmonary hypertension in lupus patients Source: Reuters Medical News Date: February 08, 2000 http://www.reuters.gov/archive/2000/02/08/professional/links/20000 208clin012.html

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·

Prostacyclin improves exercise function in patients with worsening pulmonary hypertension Source: Reuters Medical News Date: November 30, 1999 http://www.reuters.gov/archive/1999/11/30/professional/links/19991 130clin002.html

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Continuous prostacyclin improves secondary pulmonary hypertension Source: Reuters Medical News Date: May 04, 1999 http://www.reuters.gov/archive/1999/05/04/professional/links/19990 504clin003.html

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Noninvasive predictor of hemodynamic status in patients with primary pulmonary hypertension identified Source: Reuters Medical News Date: January 14, 1999 http://www.reuters.gov/archive/1999/01/14/professional/links/19990 114clin005.html

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Digoxin potentially useful in patients with primary pulmonary hypertension Source: Reuters Medical News Date: October 06, 1998 http://www.reuters.gov/archive/1998/10/06/professional/links/19981 006clin008.html

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Atrial septostomy useful in severe pulmonary hypertension Source: Reuters Medical News Date: August 03, 1998 http://www.reuters.gov/archive/1998/08/03/professional/links/19980 803clin001.html

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Hole in heart helps pulmonary hypertension Source: Reuters Health eLine Date: July 31, 1998 http://www.reuters.gov/archive/1998/07/31/eline/links/19980731elin 009.html

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AIDS-related CMV lung infection can lead to pulmonary hypertension Source: Reuters Medical News Date: July 30, 1998 http://www.reuters.gov/archive/1998/07/30/professional/links/19980 730clin003.html

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No link between dexfenfluramine, pulmonary hypertension in rats Source: Reuters Medical News Date: May 13, 1998 http://www.reuters.gov/archive/1998/05/13/professional/links/19980 513scie001.html

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Epoprostenol Improves Vascular Resistance In Pulmonary Hypertension Source: Reuters Medical News Date: January 29, 1998 http://www.reuters.gov/archive/1998/01/29/professional/links/19980 129clin001.html

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Drug Treats Pulmonary Hypertension Source: Reuters Health eLine Date: January 28, 1998 http://www.reuters.gov/archive/1998/01/28/eline/links/19980128elin 009.html

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Epoprostenol Improves Survival And QOL In Patients With Primary Pulmonary Hypertension Source: Reuters Medical News Date: August 01, 1997 http://www.reuters.gov/archive/1997/08/01/professional/links/19970 801clin002.html

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Pulmonary Hypertension Contributes To Mortality In HIV Patients Source: Reuters Medical News Date: March 25, 1997 http://www.reuters.gov/archive/1997/03/25/professional/links/19970 325clin009.html

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Gene For Familial Primary Pulmonary Hypertension Localized Source: Reuters Medical News Date: March 03, 1997 http://www.reuters.gov/archive/1997/03/03/professional/links/19970 303scie001.html

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Obesity Drugs Increase Risk Of Pulmonary Hypertension Source: Reuters Medical News Date: August 29, 1996 http://www.reuters.gov/archive/1996/08/29/professional/links/19960 829clin001.html

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Severe pulmonary hypertension may improve with oral beraprost Source: Reuters Industry Breifing Date: December 25, 2001 http://www.reuters.gov/archive/2001/12/25/business/links/20011225 clin001.html

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Serotonin transporter key in pathogenesis of primary pulmonary hypertension Source: Reuters Medical News Date: October 31, 2001 http://www.reuters.gov/archive/2001/10/31/professional/links/20011 031scie002.html

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Endothelin-receptor blocker shown beneficial in pulmonary hypertension Source: Reuters Industry Breifing Date: October 04, 2001 http://www.reuters.gov/archive/2001/10/04/business/links/20011004 clin006.html

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Genetic basis of primary pulmonary hypertension clarified Source: Reuters Medical News Date: August 01, 2001 http://www.reuters.gov/archive/2001/08/01/professional/links/20010 801clin006.html

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Epoprostenol effective for HIV-associated pulmonary hypertension Source: Reuters Medical News Date: December 04, 2000 http://www.reuters.gov/archive/2000/12/04/professional/links/20001 204clin006.html

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Gene responsible for many cases of familial primary pulmonary hypertension identified Source: Reuters Industry Breifing Date: July 24, 2000 http://www.reuters.gov/archive/2000/07/24/business/links/20000724 scie003.html

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Long-term iloprost aerosol therapy effective in primary pulmonary hypertension Source: Reuters Industry Breifing Date: June 22, 2000 http://www.reuters.gov/archive/2000/06/22/business/links/20000622 clin002.html

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Double lung transplantation unnecessary for patients with secondary pulmonary hypertension Source: Reuters Medical News Date: March 23, 2000 http://www.reuters.gov/archive/2000/03/23/professional/links/20000 323clin004.html

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[] - Redux Label To Change: Risk Of Pulmonary Hypertension Higher Than Thought Source: Reuters Medical News Date: August 26, 1996 http://www.reuters.gov/archive/1996/08/26/professional/links/19960 826xxxx001.html

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Aerosolized Prostacyclin And Iloprost May Relieve Pulmonary Hypertension Source: Reuters Medical News Date: May 13, 1996 http://www.reuters.gov/archive/1996/05/13/professional/links/19960 513clin010.html

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Primary Pulmonary Hypertension In HIV: The Influence Of HLA Class II Alleles Source: Reuters Medical News Date: April 16, 1996 http://www.reuters.gov/archive/1996/04/16/professional/links/19960 416clin010.html

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Prostacyclin Improves Survival In Patients With Primary Pulmonary Hypertension Source: Reuters Medical News Date: February 01, 1996 http://www.reuters.gov/archive/1996/02/01/professional/links/19960 201clin007.html

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Lancing The Atrial Septum Prolongs Survival In Patients With Primary Pulmonary Hypertension Source: Reuters Medical News Date: April 14, 1995 http://www.reuters.gov/archive/1995/04/14/professional/links/19950 414clin002.html

Periodicals and News 99

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 http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their 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.

Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “primary pulmonary hypertension” (or synonyms). As this service is oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about. Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo: http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “primary pulmonary hypertension” (or synonyms). If you know the name of a company that is relevant to primary pulmonary hypertension, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks.

100 Primary Pulmonary Hypertension

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 “primary pulmonary hypertension” (or synonyms).

Newsletter Articles If you choose not to subscribe to a newsletter, you can nevertheless find references to newsletter articles. We recommend that you use the Combined Health Information Database, while limiting your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. To access this databse, 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.” By making these selections, and typing in “primary pulmonary hypertension” (or synonyms) into the “For these words:” box, you will only receive results on newsletter articles. You should check back periodically with this database as it is updated every 3 months. The following is a typical result when searching for newsletter articles on primary pulmonary hypertension: ·

The New Diet Pill: Is It For You? Source: Reader's Digest. p43-48, September 1996. Summary: This article summarizes the findings of several studies of dexfenfluramine. Both the benefits and drawbacks are discussed. While dexfenfluramine (brand name Redux () has been shown to be effective in weight loss and weight loss maintenance, studies have also found instances of memory loss and primary pulmonary hypertension, a lifethreatening illness. On the whole, however, the author concludes, for those who have difficulty losing weight and are very obese, or have illnesses caused by obesity, Redux ( is a very effective weight-loss medication.

·

FDA Requests New Redux Labeling Source: Healthy Weight Journal. 10(6):109; November/December 1996.

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Contact: Healthy Living Institute, 402 S. 14th St., Hettinger, ND 58639. (701) 567-2645. Summary: The risk of primary pulmonary hypertension with dexfenfluramine (Redux () is higher than the drug companies originally reported, warns the Food and Drug Administration in requesting a label change of the diet drug. An extensive four-country study in Europe found the rare, but life-threatening , lung disorder to be 23 times higher for patients on the diet drug than for non-users, instead of 9 times higher, as previously reported. The longer they took the drug, the higher was their risk.

Academic Periodicals Hypertension

covering

Primary

Pulmonary

Academic periodicals can be a highly technical yet valuable source of information on primary pulmonary hypertension. We have compiled the following list of periodicals known to publish articles relating to primary pulmonary hypertension and which are currently indexed within the National Library of Medicine’s PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on primary pulmonary hypertension published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical’s name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, you can also visit 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.” The following is a sample of periodicals which publish articles on primary pulmonary hypertension:

102 Primary Pulmonary Hypertension

·

Journal of the American College of Cardiology. (J Am Coll Cardiol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+the+American+College+of+Cardiology&dispmax=20&dispstar t=0

Vocabulary Builder Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] 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] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [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] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Psychopharmacology:

The study of the effects of drugs on mental and

Periodicals and News 103

behavioral activity. [NIH] Septum: In the heart, a muscle wall separating the chambers. [NIH]

Physician Guidelines and Databases 105

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

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 Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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The NHLBI recently recommended the following guidelines and references to physicians treating patients with lung conditions: Asthma General: ·

National Asthma Education and Prevention Program Slide Sets: http://hin.nhlbi.nih.gov/naepp_slds/menu.htm

·

Action Against Asthma: A Strategic Plan for the Department of Health and Human Services: http://aspe.hhs.gov/sp/asthma

·

Asthma Management Model System (Web Site): http://www.nhlbisupport.com/asthma/index.html

·

Asthma Management in Minority Children: http://www.nhlbi.nih.gov/health/prof/lung/asthma/ast_chil.htm

·

AsthmaMemo: http://www.nhlbi.nih.gov/health/prof/lung/asthma/asth_mem.htm

·

Data Fact Sheet: Asthma Statistics: http://www.nhlbi.nih.gov/health/prof/lung/asthma/asthstat.htm

·

Diagnosing and Managing Asthma in the Elderly: http://www.nhlbi.nih.gov/health/prof/lung/asthma/as_elder.htm

·

Guidelines for the Diagnosis and Management of Asthma: NAEPP Expert Panel Report 2: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm

·

NAEPP Task Force on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care: http://www.nhlbi.nih.gov/health/prof/lung/asthma/ast_cost.htm

·

Nurses: Partners in Asthma Care: http://www.nhlbi.nih.gov/health/prof/lung/asthma/nurs_gde.htm

·

Practical Guide for the Diagnosis and Management of Asthma: http://www.nhlbi.nih.gov/health/prof/lung/asthma/practgde.htm

·

Report of the Working Group on Asthma and Pregnancy: http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.txt

·

The Role of the Pharmacist in Improving Asthma Care: http://www.nhlbi.nih.gov/health/prof/lung/asthma/asmapmcy.htm

·

World Asthma Day 2001 (May 3, 2001): http://www.nhlbi.nih.gov/health/prof/lung/asthma/wad_2/index.htm

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Schools/child care centers: ·

NAEPP Resolution on Asthma Management at School: http://www.nhlbi.nih.gov/health/public/lung/asthma/resolut.htm

·

Asthma and Physical Activity in the School: http://www.nhlbi.nih.gov/health/public/lung/asthma/phy_asth.htm

·

Asthma Awareness Curriculum for the Elementary Classroom: http://www.nhlbi.nih.gov/health/prof/lung/asthma/school/index.htm

·

How Asthma-Friendly Is Your School? (¿Su escuela tiene en cuenta a los niños con asma?): http://www.nhlbi.nih.gov/health/public/lung/asthma/friendhi.htm

·

How Asthma-Friendly Is Your Child-Care Setting? (¿Su guardería infantil tiene en cuenta a los niños con asma?): http://www.nhlbi.nih.gov/health/public/lung/asthma/child_ca.htm

·

School Asthma Education Slide Set: http://hin.nhlbi.nih.gov/naepp_slds/menu.htm

See also: ·

Asthma Clinical Research Network (ACRN): http://www.acrn.org/27

·

Global Initiative for Asthma: http://www.nhlbi.nih.gov/health/prof/lung/gina.htm

·

National Asthma Education and Prevention Program: http://www.nhlbi.nih.gov/about/naepp/index.htm National Emphysema Treatment Trial (NETT)

·

News Release: NHLBI-Funded Emphysema Study Finds Certain Patients at High Risk for Death Following Lung Surgery, August 14, 2001: http://www.nhlbi.nih.gov/new/press/01-08-14.htm

·

News Release: NHLBI/HCFA Lung Volume Reduction Surgery Study Participants Announced, December 20, 1996: http://www.nhlbi.nih.gov/health/prof/lung/nett/lvrspr.htm

·

Background and Study Information: http://www.nhlbi.nih.gov/health/prof/lung/nett/lvrsweb.htm

Please note: This link, which goes outside the NHLBI Web site, will open a new browser window; to return to this document, either close the new window, or toggle back (ALT-TAB for Windows users, Apple-TAB for Macintosh users).

27

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·

Participating Centers: http://www.nhlbi.nih.gov/health/prof/lung/nett/lvrsctr.htm Other Pulmonary Information

Global Initiative for Chronic Obstructive Lung Disease (GOLD): ·

COPD Guideline Tool for Palm OS: http://hin.nhlbi.nih.gov/copd.htm

·

Workshop Report: http://www.nhlbi.nih.gov/health/prof/lung/gold.htm

·

Tuberculosis Academic Awards: http://www.nhlbi.nih.gov/funding/training/tbaa/index.htm

·

Acute Respiratory Distress Syndrome Clinical Network (ARDSNet): http://hedwig.mgh.harvard.edu/ardsnet/

·

Pulmonary Immunobiology and Inflammation in Pulmonary Diseases NHLBI, Workshop Summary: http://www.nhlbi.nih.gov/meetings/workshops/pul_inflam.htm

·

Pharmacological Therapy for Idiopathic Pulmonary Fibrosis: Past, Present, and Future, NHLBI Workshop Summary: http://www.nhlbi.nih.gov/meetings/workshops/ipf-sum.htm

·

Nurses: Help Your Patients Stop Smoking: http://www.nhlbi.nih.gov/health/prof/lung/other/nurssmok.txt

See also: ·

List of Publications: http://www.nhlbi.nih.gov/health/pubs/pub_prof.htm

·

Information Center: http://www.nhlbi.nih.gov/health/infoctr/index.htm

·

Lung Information for Patients/Public: http://www.nhlbi.nih.gov/health/public/lung/index.htm

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.28 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).

28

Physician Guidelines and Databases 109

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:29 ·

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

·

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

·

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

·

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

·

Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

·

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

·

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

·

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

29

See http://www.nlm.nih.gov/databases/databases.html.

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·

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

·

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

·

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

While all of the above references may be of interest to physicians who study and treat primary pulmonary hypertension, the following are particularly noteworthy.

The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and primary pulmonary hypertension using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By making these selections and typing “primary pulmonary hypertension” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with primary pulmonary hypertension. The following is a sample result: ·

Cardiopulmonary Disease and Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 1997. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Website: www.lupus.org/lupus. PRICE: Available as part of a package of 21 different lupus-related brochures for $3.95 plus shipping and handling.

Physician Guidelines and Databases 111

Summary: This pamphlet for people with lupus discusses cardiopulmonary involvement in systemic lupus erythematosus (SLE). Lupus may cause inflammation of the pericardium, the myocardium, and the endocardium, as well as narrowing of the coronary arteries. The pamphlet discusses the symptoms of and treatment for pericarditis and myocarditis, and it highlights the features of endocarditis and coronary artery disease. The pamphlet describes the pulmonary manifestations of SLE, including pleuritis, pneumonitis, chronic diffuse interstitial lung disease, and pulmonary hypertension. It notes the modes of treating these pulmonary manifestations. The pamphlet stresses that early and accurate diagnosis of problems and aggressive treatment to reduce organ damage are critical to the successful management of cardiopulmonary disease in lupus. It concludes with information on the Lupus Foundation of America.

The NLM Gateway30 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.31 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.32 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “primary pulmonary hypertension” (or synonyms) into the search box and click “Search.” The

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 32 Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 30 31

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results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Items Found Journal Articles 2734 Books / Periodicals / Audio Visual 14 Consumer Health 21 Meeting Abstracts 11 Other Collections 1 Total 2781

HSTAT33 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.34 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference 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.35 Simply search by “primary pulmonary hypertension” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 35 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. 33 34

Physician Guidelines and Databases 113

Coffee Break: Tutorials for Biologists36 Some patients may wish to have access to 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. To this end, we recommend “Coffee Break,” 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.37 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.38 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at 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 a few 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/.

·

Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

·

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

·

MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms and to search medical literature, see http://www.med.virginia.edu/~wmd4n/medweaver.html.

36 Adapted

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. 38 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.

37

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·

Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see http://www.lexical.com/Metaphrase.html.

The Genome Project and Primary Pulmonary Hypertension With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to primary pulmonary hypertension. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).39 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. Go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html to search the database. Type “primary pulmonary hypertension” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for primary pulmonary hypertension:

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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·

Pulmonary Hypertension, Primary Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?178600

·

Pulmonary Hypertension, Primary Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?265400 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, Atherosclerosis, Best disease, Gaucher disease, Glucose galactose malabsorption, Gyrate atrophy, Juvenile onset diabetes, Obesity, Paroxysmal nocturnal hemoglobinuria, Phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

·

Nervous System: Mind and body. Examples: Alzheimer disease, Amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, Fragile X syndrome, Friedreich’s ataxia, Huntington disease, NiemannPick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, Spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

·

Signals: Cellular messages. Examples: Ataxia telangiectasia, Baldness, Cockayne syndrome, Glaucoma, SRY: sex determination, Tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

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·

Transporters: Pumps and channels. Examples: Cystic Fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

·

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

Physician Guidelines and Databases 117

·

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” In the box next to “for,” enter “primary pulmonary hypertension” (or synonyms) and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database40 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At the following Web site you can also search synonyms alphabetically: http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html. You can search the MCA/MR database by keywords at this Web site: http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database41 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 41 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission. 40

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knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “primary pulmonary hypertension” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to non-professionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.

Specialized References The following books are specialized references written for professionals interested in primary pulmonary hypertension (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · Atlas of Lung Pathology; Hardcover, Cd-Rom edition (July 1997), Lippincott Williams & Wilkins Publishers; ISBN: 0412112116; http://www.amazon.com/exec/obidos/ASIN/0412112116/icongroupinterna · Differential Diagnosis in Pathology: Pulmonary Disorders (Differential Diagnosis in Pathology) by Anthony A. Gal, M.D., Michael N. Koss, M.D.; Hardcover (August 1997), Lippincott, Williams & Wilkins; ISBN: 0683303015; http://www.amazon.com/exec/obidos/ASIN/0683303015/icongroupinterna · Foundations of Respiratory Care by Kenneth A. Wyka, William F. Clark, Paul J. Mathews; Hardcover - 1032 pages, 1st edition (January 15, 2002), Delmar Learning; ISBN: 0766808939; http://www.amazon.com/exec/obidos/ASIN/0766808939/icongroupinterna · Lung Disorders Sourcebook by Dawn D. Matthews; Hardcover, 1st edition (March 2002), Omnigraphics, Inc.; ISBN: 0780803396; http://www.amazon.com/exec/obidos/ASIN/0780803396/icongroupinterna · Pulmonary Diseases and Disorders Companion Handbook by Alfred P. Fishman; Paperback, 3rd edition (April 15, 2002), McGraw-Hill; ISBN: 0070220026; http://www.amazon.com/exec/obidos/ASIN/0070220026/icongroupinterna

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· Textbook of Respiratory Medicine (Two-Volume Set) by John F. Murray, Jay A. Nadel; Hardcover - 2562 pages, 3rd edition (May 15, 2000), W B Saunders Co; ISBN: 0721677118; http://www.amazon.com/exec/obidos/ASIN/0721677118/icongroupinterna

Vocabulary Builder Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Inflammation: Response of the body tissues to injury; typical signs are swelling, redness, and pain. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH]

Dissertations 121

CHAPTER 9. DISSERTATIONS ON PRIMARY PULMONARY HYPERTENSION Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to primary pulmonary hypertension. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Primary Pulmonary Hypertension ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to primary pulmonary hypertension. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with primary pulmonary hypertension:

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·

The Role of Nitric Oxide and Endothelin in the Regulation of Pulmonary Arterial Pressure in Man by Lovell, Sharon Lynne; Md from Queen's University of Belfast (northern Ireland), 2000, 209 pages http://wwwlib.umi.com/dissertations/fullcit/f1169201

Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to primary pulmonary hypertension is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

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PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with primary pulmonary hypertension and related conditions.

Researching Your Medications 125

APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with primary pulmonary hypertension. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for primary pulmonary hypertension. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of primary pulmonary hypertension. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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Your Medications: The Basics42 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of primary pulmonary hypertension. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with primary pulmonary hypertension take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment you might receive.

·

Ask how often you or your doctor will check for side effects from a given medication.

Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for primary pulmonary hypertension. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to take the medicine, how much to take, and for how long.

·

What food, drinks, other medicines, or activities you should avoid while taking the medicine.

·

What side effects the medicine may have, and what to do if they occur.

42

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

Researching Your Medications 127

·

If you can get a refill, and how often.

·

About any terms or directions you do not understand.

·

What to do if you miss a dose.

·

If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell your doctor about all the medicines you are currently taking (not just those for primary pulmonary hypertension). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

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Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for primary pulmonary hypertension. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ 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.43 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 Pharmacopoeia. It is important to read the disclaimer by the United States Pharmacopoeia (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of primary pulmonary hypertension. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to primary pulmonary hypertension:

Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

43

Researching Your Medications 129

Amphetamines ·

Systemic - U.S. Brands: Adderall; Desoxyn; Desoxyn Gradumet; Dexedrine; Dexedrine Spansule; DextroStat http://www.nlm.nih.gov/medlineplus/druginfo/amphetaminess ystemic202031.html

Anticoagulants ·

Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/anticoagulantss ystemic202050.html

Epoprostenol ·

Systemic - U.S. Brands: Flolan http://www.nlm.nih.gov/medlineplus/druginfo/epoprostenolsys temic203429.html

Heparin ·

Systemic - U.S. Brands: Calciparine; Liquaemin http://www.nlm.nih.gov/medlineplus/druginfo/heparinsystemic 202280.html

Hydralazine ·

Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/heparinsystemic 202280.html

Hydralazine and Hydrochlorothiazide ·

Systemic - U.S. Brands: Apresazide http://www.nlm.nih.gov/medlineplus/druginfo/hydralazineand hydrochlorothiaz202286.html

Isoniazid ·

Systemic - U.S. Brands: Laniazid; Nydrazid http://www.nlm.nih.gov/medlineplus/druginfo/isoniazidsystem ic202307.html

Phenoxybenzamine ·

Systemic - U.S. Brands: Dibenzyline http://www.nlm.nih.gov/medlineplus/druginfo/phenoxybenza minesystemic202458.html

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Phentolamine and Papaverine ·

Intracavernosal - U.S. Brands: Regitine http://www.nlm.nih.gov/medlineplus/druginfo/phentolaminean dpapaverineintra202459.html

Prazosin ·

Systemic - U.S. Brands: Minipress http://www.nlm.nih.gov/medlineplus/druginfo/prazosinsystemi c202475.html

Prazosin and Polythiazide ·

Systemic - U.S. Brands: Minizide http://www.nlm.nih.gov/medlineplus/druginfo/prazosinandpol ythiazidesystemi202476.html

Procainamide ·

Systemic - U.S. Brands: Promine; Pronestyl; Pronestyl-SR http://www.nlm.nih.gov/medlineplus/druginfo/procainamidesy stemic202483.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your doctor’s office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following medications are listed in the Reuters’ database as associated with primary pulmonary hypertension (including those with contraindications):44 ·

Bretylium Tosylate http://www.reutershealth.com/atoz/html/Bretylium_Tosylate.htm

·

Epoprostenol Sodium http://www.reutershealth.com/atoz/html/Epoprostenol_Sodium.htm

44

Adapted from A to Z Drug Facts by Facts and Comparisons.

Researching Your Medications 131

·

Mycophenolate Mofetil http://www.reutershealth.com/atoz/html/Mycophenolate_Mofetil.htm

·

Nifedipine http://www.reutershealth.com/atoz/html/Nifedipine.htm

·

Protamine Sulfate http://www.reutershealth.com/atoz/html/Protamine_Sulfate.htm

·

Sibutramine Hydrochloride http://www.reutershealth.com/atoz/html/Sibutramine_Hydrochloride. htm

Mosby’s GenRx Mosby’s GenRx 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. Information in Mosby’s GenRx database can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.

Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm. Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which 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. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

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Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with primary pulmonary hypertension--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat primary pulmonary hypertension or potentially create deleterious side effects in patients with primary pulmonary hypertension. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.

A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with primary

Researching Your Medications 133

pulmonary hypertension. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with primary pulmonary hypertension. The FDA warns patients to watch out for45: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)

·

Quick, painless, or guaranteed cures

·

If it sounds too good to be true, it probably isn’t true.

If you have any questions about any kind of 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, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Delmar’s Respiratory Care Drug Reference by Fred Hill; Paperback - 575 pages, 1st edition (January 15, 1999), Delmar Learning; ISBN: 0827390661; http://www.amazon.com/exec/obidos/ASIN/0827390661/icongroupinterna

·

Mosby’s Respiratory Care Drug Reference by Joseph L., Jr. Rau; Paperback - 352 pages, 1st edition (January 15, 1997), Mosby-Year Book; ISBN: 0815184565; http://www.amazon.com/exec/obidos/ASIN/0815184565/icongroupinterna

·

Pharmacology in Respiratory Care by Stuart R. Levine, Henry Hitner, Arthur J. McLaughlin, Jr.; Hardcover - 386 pages (May 11, 2001), Appleton & Lange; ISBN: 0071347275; http://www.amazon.com/exec/obidos/ASIN/0071347275/icongroupinterna

·

Respiratory Care Drug Reference by Arthur McLaughlin; Paperback - 383 pages, 2 edition (March 1997), Unknown; ISBN: 0834207885; http://www.amazon.com/exec/obidos/ASIN/0834207885/icongroupinterna

45

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

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Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Bretylium Tosylate: An agent that blocks the release of adrenergic transmitters and may have other actions. It was formerly used as an antihypertensive agent, but is now proposed as an anti-arrhythmic. [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] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Phenoxybenzamine: An alpha-adrenergic anatagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. [NIH]

Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH]

Researching Alternative Medicine 135

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to primary pulmonary hypertension. Finally, at the conclusion of this chapter, we will provide a list of readings on primary pulmonary hypertension from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.

What Is CAM?46 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also 46

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.

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known as “preventive,” which means that the practitioner educates and treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.

What Are the Domains of Alternative Medicine?47 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each.

Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are 47

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

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practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.

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Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.

Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.

Researching Alternative Medicine 139

Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.

Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.48

48

Adapted from http://www.4woman.gov/faq/alternative.htm.

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Is It Okay to Want Both Traditional and Alternative Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

Finding CAM References on Primary Pulmonary Hypertension Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for primary pulmonary hypertension. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required. 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 allow patients to search for articles that specifically relate to primary pulmonary hypertension and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “primary pulmonary hypertension” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to primary pulmonary hypertension: ·

A pulmonary hypertension-producing plant from Tanzania. Author(s): Heath D, Shaba J, Williams A, Smith P, Kombe A.

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Source: Thorax. 1975 August; 30(4): 399-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=126502&dopt=Abstract ·

Drug therapy during pregnancy. Author(s): Niebyl JR. Source: Current Opinion in Obstetrics & Gynecology. 1992 February; 4(1): 43-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1543829&dopt=Abstract

·

High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. Author(s): Rich S, Kaufmann E. Source: Journal of the American College of Cardiology. 1991 November 1; 18(5): 1323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1918710&dopt=Abstract

·

High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Author(s): Rich S, Brundage BH. Source: Circulation. 1987 July; 76(1): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2954725&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/

·

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

·

Chinese Medicine: http://www.newcenturynutrition.com/

·

drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

·

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

·

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

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·

Healthnotes: http://www.thedacare.org/healthnotes/

·

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

·

TPN.com: http://www.tnp.com/

·

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

·

WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

·

WellNet: http://www.wellnet.ca/herbsa-c.htm

·

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