The 2002 Official Patient's Sourcebook on Cystic Fibrosis

THE 2002 OFFICIAL PARENT’S SOURCEBOOK

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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 child’s physician. All matters regarding your child’s 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 administering 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 2002 Official Parent’s Sourcebook on Cystic Fibrosis: 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: 0-597-83146-7 1. Cystic Fibrosis-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 parent 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 cystic fibrosis.

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 cystic fibrosis. All of the Official Parent’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 Parent’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 Parent’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to cystic fibrosis, Official Parent’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 Idiopathic Pulmonary Fibrosis

·

The Official Patient's Sourcebook on Primary Pulmonary Hypertension

·

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 CYSTIC FIBROSIS: GUIDELINES ........ 9

Overview............................................................................................................... 9 What Is Cystic Fibrosis?..................................................................................... 11 How Common Is CF? ......................................................................................... 11 What Are the Signs and Symptoms of CF?........................................................ 12 When Should You Suspect That a Child May Have CF? .................................. 12 How Is CF Diagnosed?....................................................................................... 13 What Make CF a Genetic Disease? .................................................................... 13 How Is CF Treated?............................................................................................ 15 How Does the Gene Mutation Cause CF? ......................................................... 16 Gene Therapy – The Future of CF Treatment? .................................................. 17 Can CF Be Prevented?........................................................................................ 18 How Can Patients and Their Families and Friends Cope? ................................ 18 For More Information......................................................................................... 19 More Guideline Sources ..................................................................................... 19 Vocabulary Builder............................................................................................. 29

CHAPTER 2. SEEKING GUIDANCE ....................................................... 33

Overview............................................................................................................. 33 Associations and Cystic Fibrosis ........................................................................ 33 Finding More Associations................................................................................. 51 Finding Doctors.................................................................................................. 53 Selecting Your Doctor ........................................................................................ 54 Working with Your Child’s Doctor.................................................................... 54 Broader Health-Related Resources ..................................................................... 55 Vocabulary Builder............................................................................................. 56

CHAPTER 3. CLINICAL TRIALS AND CYSTIC FIBROSIS ........................ 59

Overview............................................................................................................. 59 Recent Trials on Cystic Fibrosis......................................................................... 62 Benefits and Risks............................................................................................... 82 Keeping Current on Clinical Trials.................................................................... 85 General References.............................................................................................. 85 Vocabulary Builder............................................................................................. 86

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 91 CHAPTER 4. STUDIES ON CYSTIC FIBROSIS.......................................... 93

Overview............................................................................................................. 93 The Combined Health Information Database ..................................................... 93 Federally-Funded Research on Cystic Fibrosis................................................... 98 E-Journals: PubMed Central ............................................................................ 103 The National Library of Medicine: PubMed .................................................... 117 Vocabulary Builder........................................................................................... 127

CHAPTER 5. PATENTS ON CYSTIC FIBROSIS ...................................... 133

Overview........................................................................................................... 133 Patents on Cystic Fibrosis ................................................................................ 134 Patent Applications on Cystic Fibrosis ............................................................ 147 Keeping Current ............................................................................................... 150 Vocabulary Builder........................................................................................... 150

CHAPTER 6. BOOKS ON CYSTIC FIBROSIS .......................................... 155

Overview........................................................................................................... 155 Book Summaries: Federal Agencies .................................................................. 155 Book Summaries: Online Booksellers ............................................................... 157 The National Library of Medicine Book Index ................................................. 160 Chapters on Cystic Fibrosis.............................................................................. 164 Directories......................................................................................................... 170 General Home References ................................................................................. 172 Vocabulary Builder........................................................................................... 172

CHAPTER 7. MULTIMEDIA ON CYSTIC FIBROSIS ............................... 181

Overview........................................................................................................... 181 Video Recordings .............................................................................................. 181 Bibliography: Multimedia on Cystic Fibrosis................................................... 182 Vocabulary Builder........................................................................................... 185

CHAPTER 8. PERIODICALS AND NEWS ON CYSTIC FIBROSIS ............ 187

Overview........................................................................................................... 187 News Services & Press Releases ....................................................................... 187 Newsletters on Cystic Fibrosis ......................................................................... 199 Academic Periodicals covering Cystic Fibrosis ................................................ 200

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 203

Overview........................................................................................................... 203 NIH Guidelines................................................................................................. 203 NIH Databases.................................................................................................. 206 Other Commercial Databases ........................................................................... 213 The Genome Project and Cystic Fibrosis.......................................................... 213 Specialized References....................................................................................... 218 Vocabulary Builder........................................................................................... 219

Contents

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PART III. APPENDICES .................................................. 221 APPENDIX A. RESEARCHING YOUR CHILD’S MEDICATIONS ........... 223

Overview........................................................................................................... 223 Your Child’s Medications: The Basics.............................................................. 224 Learning More about Your Child’s Medications ............................................. 225 Commercial Databases...................................................................................... 226 Researching Orphan Drugs.............................................................................. 227 Contraindications and Interactions (Hidden Dangers) ................................... 229 A Final Warning .............................................................................................. 230 General References............................................................................................ 231

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 233

Overview........................................................................................................... 233 What Is CAM? ................................................................................................. 234 What Are the Domains of Alternative Medicine?............................................ 234 Can Alternatives Affect My Child’s Treatment?............................................. 238 Finding CAM References on Cystic Fibrosis ................................................... 238 Additional Web Resources................................................................................ 250 General References............................................................................................ 255 Vocabulary Builder........................................................................................... 256

APPENDIX C. RESEARCHING NUTRITION ......................................... 259

Overview........................................................................................................... 259 Food and Nutrition: General Principles........................................................... 260 Finding Studies on Cystic Fibrosis .................................................................. 264 Federal Resources on Nutrition........................................................................ 269 Additional Web Resources................................................................................ 269 Vocabulary Builder........................................................................................... 270

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 273

Overview........................................................................................................... 273 Preparation ....................................................................................................... 273 Finding a Local Medical Library ...................................................................... 274 Medical Libraries Open to the Public............................................................... 274

APPENDIX E. NIH CONSENSUS STATEMENT ON GENETIC TESTING FOR CYSTIC FIBROSIS ......................................................................... 281

Overview........................................................................................................... 281 Abstract ............................................................................................................ 282 What Is Genetic Testing for Cystic Fibrosis?................................................... 283 The Current State of Knowledge ...................................................................... 285 Epidemiology .................................................................................................... 286 What Has Been Learned about Genetic Testing............................................... 288 Cystic Fibrosis Carrier Testing ........................................................................ 292 Optimal Practices for Cystic Fibrosis Genetic Testing .................................... 294 Future Directions for Research......................................................................... 297 Conclusions and Recommendations ................................................................. 298

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Contents

ONLINE GLOSSARIES.................................................... 301 Online Dictionary Directories.......................................................................... 308

CYSTIC FIBROSIS GLOSSARY..................................... 309 General Dictionaries and Glossaries ................................................................ 334

INDEX................................................................................... 336

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 all parents incorporate education into the treatment process. According to the AHRQ: Finding out more about your [child’s] condition is a good place to start. By contacting groups that support your [child’s] condition, visiting your local library, and searching on the Internet, you can find good information to help guide your decisions for your [child’s] treatment. 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 parents 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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Cystic Fibrosis

Since the late 1990s, physicians have seen a general increase in parent Internet usage rates. Parents frequently enter their children’s 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 children through sound therapies. The Official Parent’s Sourcebook on Cystic Fibrosis has been created for parents 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 cystic fibrosis, 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 cystic fibrosis. Given parents’ 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 cystic fibrosis should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your child’s best option. This sourcebook is no exception. Each child is unique. Deciding on appropriate

Introduction

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options is always up to parents in consultation with their children’s physicians and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching cystic fibrosis (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 parent networks dedicated to cystic fibrosis. It also gives you sources of information that can help you find a doctor in your local area specializing in treating cystic fibrosis. Collectively, the material presented in Part I is a complete primer on basic research topics for cystic fibrosis. Part II moves on to advanced research dedicated to cystic fibrosis. 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 cystic fibrosis. 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 “freeto-use” options. Part III provides appendices of useful background reading covering cystic fibrosis or related disorders. The appendices are dedicated to more pragmatic issues facing parents. Accessing materials via medical libraries may be the only option for some parents, 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 children with cystic fibrosis and their families.

Scope While this sourcebook covers cystic fibrosis, doctors, research publications, and specialists may refer to your child’s condition using a variety of terms. Therefore, you should understand that cystic fibrosis is often considered a synonym or a condition closely related to the following: ·

Fibrocystic Disease of Pancreas

·

Mucosis

·

Mucoviscidosis

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Cystic Fibrosis

·

Pancreatic Fibrosis

In addition to synonyms and related conditions, physicians may refer to cystic fibrosis 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 cystic fibrosis:4 ·

277.0 cystic fibrosis

·

277.00 without mention of meconium ileus

·

277.01 with meconium ileus

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 cystic fibrosis. 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 parents, 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 recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? When their child has been diagnosed with cystic fibrosis, parents will often log on to the Internet, type words into a search 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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engine, and receive several Web site listings which are mostly irrelevant or redundant. Parents are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with cystic fibrosis 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. While we focus on the more scientific aspects of cystic fibrosis, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find parent groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you and your child the most options in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your child’s 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 cystic fibrosis. The essentials typically include a definition or description of the condition, a discussion of who it affects, the signs or symptoms, tests or diagnostic procedures, and treatments for disease. Your child’s doctor or healthcare provider may have already explained the essentials of cystic fibrosis to you or even given you a pamphlet or brochure describing the condition. 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 the 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 CYSTIC FIBROSIS: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on cystic fibrosis. 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 parent in mind. Since new guidelines on cystic fibrosis 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)5 The National Institutes of Health (NIH) is the first place to search for relatively current guidelines and fact sheets on cystic fibrosis. 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. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

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

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There is no guarantee that any one Institute will have a guideline on a specific medical condition, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare disorders. 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 cystic fibrosis 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.6 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. 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 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. 6

Guidelines 11

treatment of pulmonary diseases.7 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 cystic fibrosis.

What Is Cystic Fibrosis?8 Cystic fibrosis (CF) is a chronic, progressive, and frequently fatal genetic (inherited) disease of the body’s mucus glands. CF primarily affects the respiratory and digestive systems in children and young adults. The sweat glands and the reproductive system are also usually involved. On the average, individuals with CF have a lifespan of approximately 30 years. CF-like disease has been known for over two centuries. The name, cystic fibrosis of the pancreas, was first applied to the disease in 1938.

How Common Is CF? According to the data collected by the Cystic Fibrosis Foundation, there are about 30,000 Americans, 3,000 Canadians, and 20,000 Europeans with CF. The disease occurs mostly in whites whose ancestors came from northern Europe, although it affects all races and ethnic groups. Accordingly, it is less common in African Americans, Native Americans, and Asian Americans. Approximately 2,500 babies are born with CF each year in the United States. Also, about 1 in every 20 Americans is an unaffected carrier of an abnormal “CF gene.” These 12 million people are usually unaware that they are carriers.

7 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. 8 Adapted from the National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/public/lung/other/cystfib.htm.

12 Cystic Fibrosis

What Are the Signs and Symptoms of CF? CF does not follow the same pattern in all patients but affects different people in different ways and to varying degrees. However, the basic problem is the same-an abnormality in the glands, which produce or secrete sweat and mucus. Sweat cools the body; mucus lubricates the respiratory, digestive, and reproductive systems, and prevents tissues from drying out, protecting them from infection. People with CF lose excessive amounts of salt when they sweat. This can upset the balance of minerals in the blood, which may cause abnormal heart rhythms. Going into shock is also a risk. Mucus in CF patients is very thick and accumulates in the intestines and lungs. The result is malnutrition, poor growth, frequent respiratory infections, breathing difficulties, and eventually permanent lung damage. Lung disease is the usual cause of death in most patients. CF can cause various other medical problems. These include sinusitis (inflammation of the nasal sinuses, which are cavities in the skull behind, above, and on both sides of the nose), nasal polyps (fleshy growths inside the nose), clubbing (rounding and enlargement of fingers and toes), pneumothorax (rupture of lung tissue and trapping of air between the lung and the chest wall), hemoptysis (coughing of blood), cor pulmonale (enlargement of the right side of the heart), abdominal pain and discomfort, gassiness (too much gas in the intestine), and rectal prolapse (protrusion of the rectum through the anus). Liver disease, diabetes, inflammation of the pancreas, and gallstones also occur in some people with CF.

When Should You Suspect That a Child May Have CF? CF symptoms vary from child to child. A baby born with the CF genes usually has symptoms during its first year. Sometimes, however, signs of the disease may not show up until adolescence or even later. Infants or young children should be tested for CF if they have persistent diarrhea, bulky foulsmelling and greasy stools, frequent wheezing or pneumonia, a chronic cough with thick mucus, salty-tasting skin, or poor growth. CF should be suspected in babies born with an intestinal blockage called meconium ileus.

Guidelines 13

How Is CF Diagnosed? The most common test for CF is called the sweat test. It measures the amount of salt (sodium chloride) in the sweat. In this test, an area of the skin (usually the forearm) is made to sweat by using a chemical called pilocarpine and applying a mild electric current. To collect the sweat, the area is covered with a gauze pad or filter paper and wrapped in plastic. After 30 to 40 minutes, the plastic is removed, and the sweat collected in the pad or paper is analyzed. Higher than normal amounts of sodium and chloride suggest that the person has cystic fibrosis. The sweat test may not work well in newborns because they do not produce enough sweat. In that case, another type of test, such as the immunoreactive trypsinogen test (IRT), may be used. In the IRT test, blood drawn 2 to 3 days after birth is analyzed for a specific protein called trypsinogen. Positive IRT tests must be confirmed by sweat and other tests. Also, a small percentage of people with CF have normal sweat chloride levels. They can only be diagnosed by chemical tests for the presence of the mutated gene. Some of the other tests that can assist in the diagnosis of CF are chest x-rays, lung function tests, and sputum (phlegm) cultures. Stool examinations can help identify the digestive abnormalities that are typical of CF.

What Make CF a Genetic Disease? Genes are the basic units of heredity. They are located on structures within the cell nucleus called chromosomes. The function of most genes is to instruct the cells to make particular proteins, most of which have important life-sustaining roles. Every human being has 46 chromosomes, 23 inherited from each parent. Because each of the 23 pairs of chromosomes contains a complete set of genes, every individual has two sets (one from each parent) of genes for each function. In some individuals, the basic building blocks of a gene (called base pairs) are altered (mutated). A mutation can cause the body to make a defective protein or no protein at all. The result is a loss of some essential biological function and that leads to disease. Children may inherit altered genes from one or both parents.

14 Cystic Fibrosis

Diseases such as CF that are caused by inherited genes are called genetic diseases. In CF, each parent carries one abnormal CF gene and one normal CF gene but shows no evidence of the disease because the normal CF gene dominates or “recesses” the abnormal CF gene. To have CF, a child must inherit two abnormal genes-one from each parent. The recessive CF gene can occur in both boys and girls because it is located on non-sex-linked chromosomes called autosomal chromosomes. CF is therefore called an autosomal recessive genetic disease. The inheritance patterns for the CF gene are shown in the accompanying diagram. Each child, whether male or female, has a 25 percent risk of inheriting a defective gene from each parent and of having CF. A child born to two CF patients (an unlikely event) would be at a 100 percent risk of developing CF.

Autosomal Recessive Inheritance

Guidelines 15

The presence of two mutant genes (g) is needed for CF to appear. Each parent carries one defective gene (g) and one normal gene (G). The single normal gene is sufficient for normal function of the mucus glands, and the parents are therefore CF-free. Each child has a 25 percent risk of inheriting two defective genes and getting CF, a 25 percent chance of inheriting two normal genes, and a 50 percent chance of being an unaffected carrier like the parents.

How Is CF Treated? Since CF is a genetic disease, the only way to prevent or cure it would be with gene therapy at an early age. Ideally, gene therapy could repair or replace the defective gene. Another option for treatment would be to give a person with CF the active form of the protein product that is scarce or missing. At present, neither gene therapy nor any other kind of treatment exists for the basic causes of CF, although several drug-based approaches are being investigated. In the meantime, the best that doctors can do is to ease the symptoms of CF or slow the progress of the disease so the patient’s quality of life is improved. This is achieved by antibiotic therapy combined with treatments to clear the thick mucus from the lungs. The therapy is tailored to the needs of each patient. For patients whose disease is very advanced, lung transplantation may be an option. CF was once always fatal in childhood. Better treatment methods developed over the past 20 years have increased the average lifespan of CF patients to nearly 30 years. These treatment approaches are detailed more fully below: Management of Lung Problems A major focus of CF treatment is the obstructed breathing that causes frequent lung infections. Physical therapy, exercise, and medications are used to reduce the mucus blockage of the lung’s airways. Chest therapy consists of bronchial, or postural, drainage, which is done by placing the patient in a position that allows drainage of the mucus from the lungs. At the same time, the chest or back is clapped (percussed) and vibrated to dislodge the mucus and help it move out of the airways. This process is repeated over different parts of the chest and back to loosen the mucus in different areas of each lung. This procedure has to be done for

16 Cystic Fibrosis

children by family members but older patients can learn to do it by themselves. Mechanical aids that help chest physical therapy are available commercially. Exercise also helps to loosen the mucus, stimulate coughing to clear the mucus, and improve the patient’s overall physical condition. Medications used to help breathing are often aerosolized (misted) and can be inhaled. These medicines include bronchodilators (which widen the breathing tubes), mucolytics (which thin the mucus), and decongestants (which reduce swelling of the membranes of the breathing tubes). A recent advance, approved by the Food and Drug Administration, is an inhaled aerosolized enzyme that thins the mucus by digesting the cellular material trapped in it. Antibiotics to fight lung infections also are used and may be taken orally or in aerosol form, or by injection into a vein.

Management of Digestive Problems The digestive problems in CF are less serious and more easily managed than those in the lungs. A well-balanced, high-caloric diet, low in fat and high in protein, and pancreatic enzymes (which help digestion) are often prescribed. Supplements of vitamins A, D, E, and K are given to ensure good nutrition. Enemas and mucolytic agents are used to treat intestinal obstructions.

How Does the Gene Mutation Cause CF? The CF gene was identified in 1989. Since then, a great deal has been learned about this gene and its protein product. The biochemical abnormality in CF results from a mutation in a gene that produces a protein responsible for the movement through the cell membranes of chloride ions (a component of sodium chloride, or common table salt). The protein is called CFTR--cystic fibrosis transmembrane regulator. CFTR is present in cells that line the passageways of the lungs, pancreas, colon, and genitourinary tract. When this protein is abnormal, two of the hallmarks of CF result-blockage of the movement of chloride ions and water in the lung and other cells and secretion of abnormal mucus. The mutation involved in CF causes the deletion of three of the base pairs in the gene. This in turn, causes a loss in the CFTR protein of an amino acid (the building blocks of proteins). Because phenylalanine is located in position 508 of the protein chain, this mutant protein is called deltaF508 CFTR.

Guidelines 17

However, deltaF508 CFTR accounts for only 70-80 percent of all CF cases. Various other mutations-over 400 at the last count-seem to be responsible for the remaining CF cases. Differences in disease patterns seen in individuals and families probably result from the combined effects of the particular mutation and various, but still unknown, factors in the CF patient and his or her environment.

Gene Therapy – The Future of CF Treatment? Gene therapy for CF is not yet possible but impressive progress is being made in developing ways to treat the gene abnormality that causes CF. In the laboratory, scientists have been able to grow cells from the nasal passages of CF patients. By introducing the normal gene into these cells, researchers corrected the cells’ chloride transport abnormality. The chloride defect has also been corrected in small regions in the nasal passages themselves by giving CF patients the normal gene in nose drops. Scientists are still looking for answers to many questions about gene therapy. Some of these questions are: How should the gene be packaged? What are the best ways to get the gene-containing package into the patient’s lungs? What will the long-term results of this treatment be? Can the abnormal chloride transport be corrected in other parts of the body? How long will the correction last? And, most importantly, can gene therapy cure or prevent the lung disease in CF? Is It Possible to Detect CF in an Unborn Baby? Finding out whether a baby is likely to have CF is possible using prenatal genetic tests. However, the tests cannot detect all of the CF gene mutations. Also, because these tests are very expensive and have certain risks to the mother, they are not used for all pregnant women. If there is another child with CF in the family, the expectant mother may request a prenatal test to see if the fetus has CF genes from both parents, is a carrier for one gene, or is altogether free of the CF genes. There are two special prenatal tests that can be done--either an amniocentesis or chorionic villus biopsy will be performed. In amniocentesis, cells from the fluid surrounding the baby in the mother’s womb (called the amniotic fluid) are tested to see if the CF genes common to the parents are present. In chorionic villus biopsy, cells from the tissue that will eventually form the placenta are tested for the CF gene.

18 Cystic Fibrosis

Can CF Be Prevented? At this time, preventing CF is not possible. In babies with two abnormal CF genes, the disease is already present at birth in some organs, such as the pancreas and liver, but develops only after birth in the lungs. Someday, gene therapy may be used to prevent the lung disease from developing. Yet, CF might be prevented in the future. Since CF occurs only when both parents pass on a CF gene to a child, it could be prevented by identifying all carriers of CF genes. Genetic counselors might then persuade couples who are carriers not to have children. However, as noted, current tests can detect only some of the more than 400 gene mutations and so the tests are only 8085 percent accurate. Yet, progress in gene therapy and the realization that not all CF mutations are life-threatening should reassure couples. Potential parents who carry the defective gene may choose to have children.

How Can Patients and Their Families and Friends Cope? CF education helps patients and their families face the physical and emotional effects of the disease and encourages CF patients to lead active, fulfilling lives. Educational programs and materials suitable for both patients of various ages and their parents are available from local CF centers and from local chapters of the CF Foundation. Patients and their families and friends should know that: ·

CF parents should not feel guilty or responsible for causing their child’s disease; they could not have prevented it.

·

Parents should treat their children with CF as normally as possible. They shouldn’t be over-protective but should encourage them to be active and self-reliant.

·

Family and friends should remember that CF is not contagious; nobody can get it from a patient.

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In families with CF, brothers, sisters, and first cousins of the CF patient should be tested to see if they carry a defective gene, especially if they seem to have a chronic lung or digestive problem. Carriers of the abnormal gene should get genetic counseling.

Guidelines 19

·

Individuals with CF have normal sexual development and can expect to have a normal sex life. However, most, but not all, men are infertile because of a mechanical blockage of sperm and cannot have children. Women with CF can have children, although they may be less fertile than women without CF.

·

Patients and families should work closely with doctors and other medical specialists to develop self-management skills that can improve their quality of life.

·

Above all, CF patients and their families should keep a positive attitude. Scientists continue to make significant advances in understanding the genetic and physiological disturbances in CF and in developing new treatment approaches such as gene therapy. The outlook is bright for further improvements in the care of CF patients and even for the discovery of a cure.

For More Information Additional information about CF can be obtained from the following organizations: National Heart, Lung, and Blood Institute (NHLBI) NHLBI Health Information Network P.O. Box 30105 Bethesda, MD 20824-0105 Telephone: 301-592-8573 The Cystic Fibrosis Foundation 6931 Arlington Road, #200 Bethesda, MD 20814 Telephone: 301-951-4422 or 1-800-344-4823 National Diabetes Information Clearinghouse 1 Information Way Bethesda, MD 20892-3560 Telephone: 301-654-3327 or 1-800-891-5388

More Guideline Sources The guideline above on cystic fibrosis 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

20 Cystic Fibrosis

find additional guidelines on topics related to cystic fibrosis. Many of the guidelines listed below address topics that may be of particular relevance to your child’s specific situation, while certain guidelines will apply to only some children with cystic fibrosis. 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 parents wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and parentoriented 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 can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following as being relevant to cystic fibrosis: ·

Guides On cystic fibrosis Cystic fibrosis http://www.nlm.nih.gov/medlineplus/ency/article/000107.htm Cystic Fibrosis http://www.nlm.nih.gov/medlineplus/cysticfibrosis.html Cystic Fibrosis http://www.nlm.nih.gov/medlineplus/tutorials/cysticfibrosisloader .html

·

Other Guides Directories http://www.nlm.nih.gov/medlineplus/directories.html Malabsorption http://www.nlm.nih.gov/medlineplus/ency/article/000299.htm Sinusitis http://www.nlm.nih.gov/medlineplus/ency/article/000647.htm

Within the health topic page dedicated to cystic fibrosis, the following was recently recommended to parents:

Guidelines 21

·

General/Overviews Cystic Fibrosis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?objectid=2CEBF76F-D36A4D15-B937BFF91AB51438 Cystic Fibrosis Source: Patient Education Institute http://www.nlm.nih.gov/medlineplus/tutorials/cysticfibrosisloader .html Facts About Cystic Fibrosis Source: Cystic Fibrosis Foundation http://www.cff.org/facts.htm

·

Diagnosis/Symptoms Sweat Testing Procedure and Commonly Asked Questions Source: Cystic Fibrosis Foundation http://www.cff.org/publications01.htm

·

Treatment Facts About Lung Transplantation Source: Cystic Fibrosis Foundation http://www.cff.org/publications09.htm TOBI¿ (Tobramycin Solution for Inhalation) Source: Cystic Fibrosis Foundation http://www.cff.org/cfservices03.htm

·

Specific Conditions/Aspects Caring For and Cleaning Your Nebulizer and Compressor Source: Cystic Fibrosis Foundation http://www.cff.org/home%2520line/homeline199802.htm Commonly Asked Questions About Burkholderia Cepacia Source: Cystic Fibrosis Foundation http://www.cff.org/home%2520line/homeline199710.htm Exercise - The Facts Source: Cystic Fibrosis Foundation http://www.cff.org/home%2520line/homeline199703.htm

22 Cystic Fibrosis

Reproductive Issues for Individuals with Cystic Fibrosis Source: Cystic Fibrosis Foundation http://www.cff.org/home%2520line/homeline199806.htm ·

Children Cystic Fibrosis Source: Nemours Foundation http://kidshealth.org/kid/health_problems/heart/cystic_fibrosis.ht ml Cystic Fibrosis Source: Nemours Foundation http://kidshealth.org/parent/medical/lungs/cf.html

·

From the National Institutes of Health Facts About Cystic Fibrosis Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/cf.htm

·

Latest News Bacterial Slime Clogs Cystic Fibrosis Lungs Source: 04/02/2002, National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_greenberg.html

·

Organizations Cystic Fibrosis Foundation http://www.cff.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/index.htm National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

·

Prevention/Screening Cystic Fibrosis Testing: The Decision is Yours Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZ ZJE8XUUSC&sub_cat=640

Guidelines 23

Cystic Fibrosis Testing: What Happens If Both My Partner and I are Carriers? Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZ ZQRC4JUSC&sub_cat=640 Large-Scale Genetic Testing for Cystic Fibrosis Source: American Medical Association http://www.ama-assn.org/ama/pub/category/6299.html ·

Research Bacterial Slime Clogs Cystic Fibrosis Lungs Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_greenberg.html Cystic Fibrosis Research Directions Source: National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/health/endo/pubs/cystic/cystic.htm Gene Alterations for Cystic Fibrosis May Also Account for Chronic Sinus Problems in Some Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/newsroom/releases/cf-sinus.htm Gene Therapy and Cystic Fibrosis Source: Cystic Fibrosis Foundation http://www.cff.org/publications03.htm New Theory Proposed for Cystic Fibrosis Infections Source: National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/nov2001/niaid-19.htm Progress in CF Research Source: Cystic Fibrosis Foundation http://www.cff.org/publications06.htm Scientists Sequence the Largest Bacterial Genome Yet-Pseudomonas Aeruginosa--and Open Door to Development of New Antibiotics Source: Cystic Fibrosis Foundation http://www.cff.org/news0008A.htm Young Cystic Fibrosis Patients Benefit From Early Diagnosis Source: American Academy of Pediatrics http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZ ZOHAZ62HC&sub_cat=609

24 Cystic Fibrosis

·

Teenagers Cystic Fibrosis Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/digestive/cystic_fib rosis.html

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 parent-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 educational guidelines on cystic fibrosis 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: ·

Questions and Facts About Cystic Fibrosis Source: Rockville, MD.: Cystic Fibrosis Foundation. 5 p. Contact: Available from Cystic Fibrosis Foundation. 6000 Executive Boulevard, Suite 309, Rockville, MD 20852. Summary: This brochure describes Cystic Fibrosis (CF), how it occurs and its genetic etiology, identifying CF carriers, symptoms, complications of the disease, age of onset, treatment, and the outlook for the CF patient. Also included is a description of the Cystic Fibrosis Foundation and the programs it supports.

Guidelines 25

·

For adults with cystic fibrosis: Facts on reproduction Source: Madison, WI: Great Lakes Regional Genetics Group, University of Wisconsin - Madison. 1993. 12 pp. Contact: Available from National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA 221822536. Telephone: (703) 356-1964 or (888) 434-4MCH / fax: (703) 821-2098 / e-mail: [email protected] / Web site: http://www.nmchc.org. Available at no charge. Summary: This pamphlet, aimed at adults with cystic fibrosis who want to have a child, describes how the disease might have affected the male and female reproductive organs, how to overcome or circumvent these problems, and the genetics of the disease, so that the couple can make an informed choice. [Funded by the Maternal and Child Health Bureau].

·

Cystic fibrosis: Guidelines for care for children with special health care needs Source: Minneapolis, MN: Services for Children with Handicaps, Minnesota Department of Health. 1990. 60 pp. Contact: Available from Minnesota Children with Special Health Care Needs, 717 Delaware Street, S.E., Box 9441, Minneapolis, MN 55440. Telephone: (612) 623-5150 or (800) 728-5420. Summary: This publication was developed for families and health professionals caring for children with cystic fibrosis. The guidelines are aimed at helping families coordinate the health care needed for the optimal growth and development of their child. General information concerning cystic fibrosis is provided along with an overview of the family centered health care team approach to treating a child or adolescent with this metabolic disorder. The publication also outlines the child's needs at various stages of her life in terms of health care, development, school, and child care. A glossary and list of resources are also included. 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 “cystic fibrosis” or synonyms. The following was recently posted:

26 Cystic Fibrosis

·

Genetic testing for cystic fibrosis. Source: National Institutes of Health (NIH) Consensus Development Panel on Genetic Testing for Cystic Fibrosis.; 1997 April; 38 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0419&sSearch_string=cystic+fibrosis 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: ·

Check Your Cystic Fibrosis I.Q. Summary: Test your knowledge of cystic fibrosis. Answer true or false to the statements online and find out what you know or don't know about this respiratory disease. Source: American Association for Respiratory Care http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6169

·

Cystic Fibrosis Research Directions Summary: In recent years, the pace of basic research has increased rapidly, and scientists hope to translate new knowledge about the molecular basis of the disease to new therapies to improve the lives of Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=1135

Guidelines 27

·

Facts About Cystic Fibrosis Summary: Written for consumers, this brochure presents a general overview of cystic fibrosis (CF) -- a chronic, progressive, and frequently fatal genetic disease of the body's mucus glands that primarily Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=1144

·

Find a Cystic Fibrosis Care Center Summary: Visit this web site to locate a cystic fibrosis supported-care center in your area accredited by the Cystic Fibrosis Foundation. Source: Cystic Fibrosis Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4954

·

Gene Therapy and Cystic Fibrosis Summary: A patient education brochure that discusses gene therapy as a potentially a life-saving treatment that tackles the root cause of cystic fibrosis (CF), rather than the symptoms. Source: Cystic Fibrosis Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5032

·

Sweat Testing Procedure and Commonly Asked Questions Summary: This online fact sheet answers some of the commonly asked questions about the sweat test, a diagnostic procedure for Cystic Fibrosis. Source: Cystic Fibrosis Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5014

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-WEB-

28 Cystic Fibrosis

SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to cystic fibrosis. 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 parents. 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.

PEDBASE PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than parents, you can view the current list of conditions covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm.

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

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

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

·

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

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

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

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

Guidelines 29

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: Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Airways: Tubes that carry air into and out of the lungs. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Antibiotic: A drug that kills or inhibits the growth of bacteria. [NIH] Anus: The distal or terminal orifice of the alimentary canal. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bronchial: Pertaining to one or more bronchi. [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] 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] Decongestant: An agent that reduces congestion or swelling. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Enema: A clyster or injection; a liquid injected or to be injected into the rectum. [EU] Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH] Fatal: Causing death, deadly; mortal; lethal. [EU] Fetus: Unborn offspring from 7 or 8 weeks after conception until birth. [NIH] Fibrosis: Process by which inflamed tissue becomes scarred. [NIH] Genitourinary: Pertaining to the genital and urinary organs; urogenital;

30 Cystic Fibrosis

urinosexual. [EU] Hemoptysis: Coughing up blood or blood-stained sputum. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Ileus: Obstruction of the intestines. [EU] Inflammation: Response of the body tissues to injury; typical signs are swelling, redness, and pain. [NIH] Intestinal: Pertaining to the intestine. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [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] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucus: A thick fluid produced by the lining of some organs of the body. [NIH]

Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the islets of langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Placenta: The special tissue that joins the mother to her fetus; it provides the fetus with oxygen, water, and nutrients (food) from the mother's blood and secretes the hormones necessary for successful pregnancy. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Prenatal: Occurring before birth. [NIH]

Guidelines 31

Prolapse: 1. the falling down, or sinking, of a part or viscus; procidentia. 2. to undergo such displacement. [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]

Pulmonary: Relating to the lungs. [NIH] Rectal: Pertaining to the rectum (= distal portion of the large intestine). [EU] Respiratory: Pertaining to respiration. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Sinusitis: Inflammation of a sinus. The condition may be purulent or nonpurulent, acute or chronic. Depending on the site of involvement it is known as ethmoid, frontal, maxillary, or sphenoid sinusitis. [EU] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sputum: Matter ejected from the lungs, bronchi, and trachea, through the mouth. [EU] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH]

Seeking Guidance 33

CHAPTER 2. SEEKING GUIDANCE Overview Some parents are comforted by the knowledge that a number of organizations dedicate their resources to helping people with cystic fibrosis. These associations can become invaluable sources of information and advice. Many associations offer parent support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your child’s physician can be a valuable source of guidance and support. In this chapter, we direct you to resources that can help you find parent organizations and medical specialists. We begin by describing how to find associations and parent groups that can help you better understand and cope with your child’s condition. The chapter ends with a discussion on how to find a doctor that is right for your child.

Associations and Cystic Fibrosis In addition to associations or groups that your child’s 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 child’s insurance provider to find out if the cost will be covered):

Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 9

34 Cystic Fibrosis

·

Australian Lung Foundation Address: Australian Lung Foundation PO Box 119, Samford, Queensland, 4520, Australia Telephone: 07 3832 2245 Toll-free: 1800 654 301 Fax: 07 3832 145 Email: [email protected] Web Site: http://www.lungnet.org.au Background: The Australian Lung Foundation (ALF) is a not-for-profit organization that is committed to improving the quality of life of individuals affected by lung disease and promoting lung health in Australia. Established in 1990, the Foundation works to fulfill its mission by raising funds in support of lung disease research, distributing research findings, educating patients and the broader public on the treatment and prevention of lung disease, fostering patient support activities, and influencing public and corporate policy to ensure safe living and working environments. The ALF's activities include providing annual research grants and awards; working with industries to enhance employee safety and corporate productivity; and conducting conferences that are open to all members of the respiratory and wider medical community, government and corporate bodies, special interest groups, and patient support organizations. The Foundation's objectives include establishing the ALF Collaborative Research Institute to facilitate cooperative research and interaction both nationally and internationally and provide a centralized data collection site for respiratory disease; creating multidisciplinary consultative groups to enhance collaboration, generate educational material, and provide a source of expert opinion and comment on lung disease issues; and establishing a national network of patient support groups. The Foundation also provides educational materials including patient information leaflets and maintains a web site on the Internet. Relevant area(s) of interest: Cystic Fibrosis

·

Canadian Cystic Fibrosis Foundation Address: Canadian Cystic Fibrosis Foundation 2221 Yonge Street, Suite 601, Toronto, Ontario, M4S 2B4, Canada Telephone: (416) 485-9149 Toll-free: (800) 378-2233 Fax: (416) 485-0960 Email: [email protected] or [email protected] Web Site: http://www.ccff.ca/~cfwww/index.html

Seeking Guidance 35

Background: The Canadian Cystic Fibrosis Foundation (CCFF) is a national not- for-profit organization dedicated to helping individuals with cystic fibrosis (CF) and their family members. Cystic fibrosis is a rare inherited disorder that affects many exocrine ('outward-secreting') glands of the body including the sweat glands, salivary glands, and those within the pancreas and respiratory system. Due to unusually thick secretions of mucus that clog and obstruct air passages of the lungs, affected individuals experience chronic coughing and an increased susceptibility to repeated lung infections. Individuals with CF also exhibit an inability to break down food and absorb fats and nutrients properly; have abnormally salty sweat containing elevated levels of chloride and sodium; and/or may demonstrate other abnormalities. Established in 1960, the Canadian Cystic Fibrosis Foundation is committed to conducting research into improved care and treatment for CF, seeking a cure or control for the disorder, and promoting public awareness. In addition, the Foundation offers support groups, engages in patient advocacy, provides referrals, and promotes patient, professional, and general education. The Canadian Cystic Fibrosis Foundation also offers a variety of materials including brochures, guides and manuals, reports, and several newsletters. The Foundation's web site on the Internet is located at http://www.ccff.ca/~cfwww/index.html. Relevant area(s) of interest: Cystic Fibrosis, Mucoviscidosis, Pancreatic Fibrosis ·

Case Western Reserve University Cystic Fibrosis and Pediatric Pulmonary Disease Center Department of Medicine Rainbow Babies and Childrens Hospital School of Medicine Address: 11100 Euclid Avenue Cleveland, OH 44106 Telephone: (216) 368-4370 Email: [email protected] Web Site: http://www.uhrainbow.com/ Background: The Cystic Fibrosis and Pediatric Pulmonary Disease Center is operated in cooperation with the Rainbow Babies and Childrens Hospital. It conducts both basic and applied research and provides healthcare services. The Center's specific interests include education, research, and patient care in cystic fibrosis and pediatric pulmonary disorders; gene therapy; CFTR electrophysiology; pulmonary defense mechanisms; biomechanics of the respiratory system; respiratory organ culture; antibiotics for respiratory infection; epithelial cell culture; transport by secretory epithelium; pseudomonas and other bacterial lung infection; and inflammation. Staff answer inquiries, provide advisory

36 Cystic Fibrosis

services, conduct seminars and workshops, and make referrrals to other sources of information. Services are primarily for patients, health professionals, health science students, and lay groups with special interests. Publication(s): Books; technical reports; standards; critical reviews; stateof-the-art reviews; journal articles. Relevant area(s) of interest: Cystic fibrosis; demographic data covering 1957 to the present.; Electrophysiology; Gene transfer; Holdings; Lung diseases; patients with cystic fibrosis (living and deceased), including; Pediatric respiratory diseases; pulmonary function data, microbiology sputum data, and; Respiratory physiology; The Center maintains a computerized file of more than 1,000 ·

Children's Hospital of Michigan Department of Pediatrics Division of Pulmonary Diseases: Cystic Fibrosis Care Teaching and Resource Center Address: 3901 Beaubien Blvd. Detroit, MI 48201 Telephone: (313) 745-5541 Fax: (313) 993-0390 Web Site: http://www.dmc.org/major_clinical_services/pediatrics/ Background: Childrens' Hospital of Michigan is a tertiary care facility and serves as a teaching hospital of Wayne State University Medical School. The Cystic Fibrosis Center at CHM has 4 satellites; 3 for adult of care. There is an approved apnea program serving the greater Detroit area. Children's also has an established Home Ventilatory Care Program that cares for infants and children requiring long-term mechanical ventilation. Key study areas include cystic fibrosis, clinical research and basic study relating to cytokines and inflammatory mediators; nutrition in chronic lung diseases; lung injury in premature infants. Relevant area(s) of interest: Cystic fibrosis; Inhalation therapy; Lung diseases; Pediatrics; Pulmonary function tests; Respiratory diseases; Respiratory physiology; Thoracic diseases; Tuberculosis

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Children's Liver Alliance Address: Children's Liver Alliance 3835 Richmond Avenue, Suite 190, Staten Island, NY 10312-3828 Telephone: (718) 987-6200 Fax: (718) 987-6200 Email: [email protected]

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Web Site: http://livertx.org Background: The Children's Liver Alliance (formerly the Biliary Atresia and Liver Transplant Network) is an international not-for-profit voluntary health organization that was established in 1995. The mission of the Children's Liver Alliance (CLA) is to empower the hearts and minds of children with liver disease, their families, and the medical professionals who care for them. CLA disseminates educational information about pediatric liver diseases and transplantation via written publications, seminars, and the Internet. CLA provides a support network for families of children with liver disease (both pre- and postliver transplantation), acts as liaison between families and health care professionals, offers networking services, and promotes the importance of organ donation and tranplantation. CLA's publications include the bimonthly newsletter 'The Biliary Tree.'. Relevant area(s) of interest: Cystic Fibrosis ·

Children's Liver Disease Foundation (UK) Address: Children's Liver Disease Foundation (UK) AXA Equity and Law House, 35-37 Great Charles Street Queensway, Birmingham, B3 3JY, United Kingdom Telephone: 0121 212 3839 Fax: 0121 212 4300 E- mail: [email protected] Web Site: http://www.childliverdisease.org Background: The Children's Liver Disease Foundation (UK) is a voluntary not- for-profit organization in the United Kingdom that was established in 1980. The Foundation is committed to providing emotional support to children, adolescents, and families affected by liver disease; promoting research into the causes of pediatric liver disease; creating a greater awareness of such disorders and conditions in the health care communities and the public; and promoting the development of means of early diagnosis and cure. The Children's Liver Disease Foundation is also dedicated to providing understandable information on pediatric liver disease through general informational brochures including 'A Guide to the Liver' and 'Signs and Symptoms of Liver Disease' as well as a leaflet series on specific pediatric liver diseases and conditions, such as Alagille syndrome; neonatal hepatitis; hepatitis A, B, C, and E; biliary atresia; and others. The Foundation's web site on the Internet discusses the organization's mission, goals, and services; enables interested individuals, family members, and health care professionals to make specific inquiries; and provides access to the Foundation's publication series.

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Relevant area(s) of interest: Cystic Fibrosis ·

Children's Memorial Hospital Cystic Fibrosis Research Center Northwestern University Address: 2300 Children's Plaza, Box #43 Chicago, IL 60614 Telephone: (773) 880-4382 Web Site: http://www.childmmc.edu Background: Sponsored by the Cystic Fibrosis Foundation, the Cystic Fibrosis Research Center conducts research, offers medical care, and provides teaching at the postgraduate level. Its interests include cystic fibrosis and pediatric pulmonary and gastrointestinal diseases. The staff answers inquiries; provides advisory and reference services and information on research in progress; conducts seminars; distributes publications of the Cystic Fibrosis Foundation. Relevant area(s) of interest: Cystic fibrosis; Lung diseases; Pediatrics; Respiratory diseases

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Children's Special Health Care Service Michigan Department of Community Health Address: 320 South Walnut Street Lansing, MI 48913 Lewis Cass Building - Sixth Floor Telephone: (517) 335-9261; (800) 788-7889 (TDD); 1-800-359-3722 Web Site: http://www.mdch.state.mi.us/msa Background: Children's Special Health Care Services (CSHCS) is a program within the Department of Community Health. It is for children and some adults with special health care needs and their families. It helps persons with chronic health problems by providing: coverage and referral for specialty services, based on the child's health problems; family centered services to support the caretaker of the child; community-based services to help care for the child at home and maintain normal routines; culturally competent services which demonstrate awareness of cultural differences; and coordinated services to pull together the services of many different providers who work within different agencies. Children must have a qualifying medical condition and be 20 years old or under. Persons 21 and older with cystic fibrosis or certain blood clotting disorders may also qualify for services. CSHCS covers more than 2,000 diagnoses.

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Relevant area(s) of interest: Children's health insurance; Children's special health care; Health insurance; Michigan; State sponsored health care ·

Cystic Fibrosis Clinic and Pediatric Pulmonary Center Department of Pediatrics Section of Pulmonary Diseases Tulane University School of Medicine Address: 1430 Tulane Avenue New Orleans, LA 70112 Telephone: (504) 588-5601 Fax: (504) 588-5490 Web Site: http://www.mcl.tulane.edu/departments/peds_respcare/default.htm; Internet Address: Background: The Cystic Fibrosis Clinic and Pediatric Pulmonary Center is sponsored by the Maternal and Child Health Office of the U.S. Department of Health and Human Services and the Louisiana State Handicapped Children's Services. The Center conducts research, provides training, and offers treatment in pediatric pulmonary diseases. Interests include pediatric pulmonary diseases, cystic fibrosis, asthma, allergic airway disease, and disorders in control of ventilation, including apnea and near-miss SIDS. The Center has a large repository of data on pulmonary diseases in children, including anthropometry and pulmonary function data. Patient data are computer based. The Center answers inquiries, provides advisory and consulting services, conducts seminars, evaluates data, and makes referrals to other sources of information. Relevant area(s) of interest: Apnea; Asthma; Bronchopulmonary dysplasia; Cystic fibrosis; Lung diseases; Pediatric respiratory diseases; Sudden infant death syndrome

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Cystic Fibrosis Foundation Address: Cystic Fibrosis Foundation 6931 Arlington Road, Bethesda, MD 20814 Telephone: (301) 951-4422 Fax: (301) 951-6378 Toll- free: (800) 344-4823 Email: [email protected] Web Site: http://www.cff.org Background: The Cystic Fibrosis Foundation (CFF) is a voluntary not-forprofit organization dedicated to raising funds for research to find a cure

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for cystic fibrosis (CF) and improving the quality of life for individuals with the disease. Cystic fibrosis is a rare inherited disorder that affects many exocrine ('outward-secreting') glands of the body including the sweat glands, salivary glands, and those within the pancreas and respiratory system. Established in 1955 and currently consisting of more than 70 chapters and branch offices across the country, the Cystic Fibrosis Foundation funds its own network of CF research centers at leading universities and medical schools throughout North America. It provides a variety of grants to scientists to fund CF research and finances over 100 CF care centers nationwide. The organization supports clinical trials at its care centers to test new drug therapies for CF and works closely with Congress, the Food and Drug Administration, and pharmaceutical companies to speed the development of new drugs to treat CF. The Foundation offers affected individuals, family members, health care professionals, and the public a variety of informational materials including research updates, regular newsletters, and brochures on several topics such as health insurance and financial assistance programs. Relevant area(s) of interest: Cystic Fibrosis, Fibrocystic Disease of Pancreas, Mucoviscidosis, Pancreatic Fibrosis ·

Cystic Fibrosis Research Center Department of Pulmonary Diseases Indiana University Riley Hospital Address: 702 Barn Hill Drive Indianapolis, IN 46202-5225 Telephone: (317) 274-7208 Web Site: http://www.iupui.edu/home/riley.html Background: The Cystic Fibrosis Research Center is a non-profit organization. Interests of the Center include cystic fibrosis basic research and clinical aspects of cystic fibrosis, pulmonary function, related pulmonary diseases, and infant lung function. The Center answers inquiries; provides reference, abstracting, and indexing services; conducts seminars and workshops; and distributes publications. Services are free, unless extensive; and are available to laymen, parents, teachers, and professionals. Publication(s): Abstracts; indexes; directories; bibliographies; data compilations; reprints. Relevant area(s) of interest: Cystic fibrosis; Lung diseases; Medical research; Respiratory physiology

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Cystic Fibrosis Research, Inc Address: Cystic Fibrosis Research, Inc. 560 San Antonio Road, Suite 103, Palo Alto, CA 94306 Telephone: (650) 856-0546 Fax: (650) 856-0554 Email: [email protected] Web Site: http://www.cfri.org Background: Cystic Fibrosis Research, Inc. (CFRI) is an independent, notfor- profit, voluntary healthy organization dedicated to offering emotional and educational support to families living with cystic fibrosis (CF). Cystic fibrosis is a genetic disorder that affects many exocrine glands of the body including the sweat glands, salivary glands, and glands within the pancreas and respiratory system. Associated characteristics include susceptibility to repeated lung infections, an impaired ability to absorb fats and other nutrients from food, abnormally salty sweat containing elevated levels of chloride and sodium, and/or other abnormalities. Cystic fibrosis is inherited as an autosomal recessive genetic trait. Established in 1975 and currently consisting of approximately 14,000 members, Cystic Fibrosis Research, Inc. is committed to providing a variety of educational and support programs for affected families including mail and telephone referrals and support services, regular membership meetings, parent support groups, CF support groups for ages 13 to adult, an annual conference, and a family retreat. The organization also funds cystic fibrosis research at major research centers in the U.S., supports ongoing gene therapy research, and offers community educational programs. Cystic Fibrosis Research, Inc. also provides a variety of educational materials including a video lending library; brochures, such as a teacher's guide to CF; a children's newsletter entitled 'The Cackler'; and a regular newsletter for affected families and professionals entitled 'CFRI News.' The organization also has a web site on the Internet. Relevant area(s) of interest: Cystic Fibrosis, Fibrocystic Disease of Pancreas, Mucosis, Mucoviscidosis, Pancreatic Fibrosis

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Cystic Fibrosis Trust Address: Cystic Fibrosis Trust Alexandria House, 5 Blyth Road, Bromley, Kent, BR1 3RS, United Kingdom Telephone: 0181 464 721 Fax: 0181 313 0472

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Background: The Cystic Fibrosis Trust is a voluntary organization in the United Kingdom dedicated to raising funds for hospital and medical research into improved treatment and prevention of cystic fibrosis (CF), a rare inherited disorder that affects many exocrine ('outwardly-secreting') glands of the body including the sweat glands, salivary glands, and those within the pancreas and respiratory system. Established in 1964, the Cystic Fibrosis Trust has approximately 16,000 members in 300 chapters throughout the United Kingdom. The CF Trust provides a network of support groups for affected individuals and family members and offers several materials including brochures, pamphlets, fact sheets, and videos. Relevant area(s) of interest: Cystic Fibrosis, Fibrocystic Disease of Pancreas, Mucosis, Mucoviscidosis, Pancreatic Fibrosis ·

Department of Human Genetics Molecular Genetics Laboratory University of Pittsburgh Address: E1650 Biomedical Science Tower Pittsburgh, PA 15261 Telephone: (800) 334-7980 (Toll-free) Web Site: http://www.pitt.edu/~geneorb Background: The University of Pittsburgh Molecular Genetics Diagnostic Laboratory provides information and counseling on Gaucher disease and other genetic (inherited) disorders including cystic fibrosis, Fanconi anemia, Canavan disease, and Tay Sachs disease. The Laboratory is an active research center which includes studies in gene therapy. Diagnosis; testing and evaluation; and treatment and management are also offered. The organization publishes a journal, and it sponsors training seminars. Relevant area(s) of interest: Gauchers disease; Gene therapy; Genetic counseling; Genetic disorders; Metabolic diseases

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Department of Pediatrics Intermountain Cystic Fibrosis Center University of Utah Hospitals and Clinics Address: 50 North Medical Drive Salt Lake City, UT 84132 Telephone: (801) 585-2804; (801) 585-3187 (Clinical Coordinator) Fax: (801) 585-2661 Email: [email protected] Web Site: http://www.med.utah.edu/pulm/cf.htm Background: The Intermountain Cystic Fibrosis Center (ICFC), based at the University of Utah Hospital and Clinics and Primary Children's Medical Center, provides Health Care to patients with cystic fibrosis in the Intermountain Region. While the majority of these patients are

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concentrated along the Wasatch Front and Southern Idaho, patients come to our hospitals from as far away as Kailispell, Montana; Jackson Hole, Wyoming, Reno, Nevada and St. George, Utah. The Intermountain Cystic Fibrosis Center is one of the largest CF Centers in the Intermountain Region. To maintain this status one must meet clearly-defined clinical, teaching, research, and community outreach requirements. Relevant area(s) of interest: Child health; Cystic fibrosis; Medical care; Medical education; Medical research; Pulmonary diseases ·

Department of Physiology and Biophysics School of Medicine University of Alabama at Birmingham Address: 1918 University Boulevard Birmingham, AL 35294-0005 Telephone: (205) 934-4186 Fax: (205) 934-1445 Web Site: http://www.physiology.uab.edu/ Background: The Department of Physiology and Biophysics is one of several Joint Health Sciences departments administered by the Schools of Medicine and Dentistry at UAB. Over 40 faculty members educate, train, and assist the Department's graduate students and postdoctoral fellows in their investigation of a wide variety of physiological processes, human physiology, cell biology, and biostatistics. Specific areas of research include neurosciences; sodium and chloride channels; reproductive physiology; transport across membranes; respiratory physiology; endocrinology; neural control of heart and circulation; central mechanisms in hypertension; genetic hypertension; neuroendocrinology; and renal physiology. Relevant area(s) of interest: Biostatistics; Cell biology; chloride channels; Cystic fibrosis; Endocrinology; Exocrine secretion; Human physiology; Hypertension; Membranes; Neuroendocrinology; Neurosciences; Renal physiology; Reproductive physiology; Respiratory physiology; Sodium channels

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Grant A Wish Foundation Address: Baltimore, MD 21228 PO Box 21243 Telephone: (800) 933-5470 Web Site: http://www.grant-a-wish.org Background: Grant A Wish is a national children's charity that provides educational, recreational and supportive services to children, 18 and under, who are battling life-threatening illnesses. Headquartered in

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Baltimore, Maryland, it offers services that provide comfort and hope to kids suffering from dancer, leukemia, cystic fibrosis, neurological diseases and various other critical illnesses. In addition to Wish Granting, it also offers eight additional programs, including support group sponsorship and hospital housing, that provide support to critically ill children and their families throughout the treatment process. Relevant area(s) of interest: Seriously-ill children; Terminally-ill children ·

Hahnemann Cystic Fibrosis Hahnemann University

and

Pediatric

Pulmonary

Center

Address: 230 North Broad Street Philadelphia, PA 19102 Telephone: (215) 762-7766 Web Site: http://www.mcphu.edu/medschool/ Background: The Hahnemann Cystic Fibrosis and Pediatric Pulmonary Centers are partially sponsored by the Pennsylvania Bureau of Crippled Children's Services, the Cystic Fibrosis Foundation, and the Variety Club of Philadelphia, as well as research grants and private donations. Their interests include research, education, and care of patients with pediatric pulmonary disease and cystic fibrosis. The Centers answer inquiries, provide advisory and consulting services, provide information on research in progress, evaluate data, conduct seminars and workshops, make referrals to other sources of information, and permit onsite use of collections. Services are free and available to those in the health services fields. Relevant area(s) of interest: Cystic fibrosis; Lung diseases; Medical care; Medical education; Medical research; Pediatrics ·

Health Services Research Unit Medical School University of Aberdeen Address: Aberdeen AB25 2ZD, Scotland Foresterhill Telephone: +44 (0) 1224-553909 Fax: +44 (0) 1224-663087 Email: [email protected] Web Site: http://www.abdn.ac.uk/public_health/hsru Background: Tthe Health Services Research Unit (HSRU) has a national grant to research the best ways to provide health care, and to train those working in the health services in research methods. Most research projects aim to find out whether developments within the health service really are effective, efficient and appropriate. HSRU has four primary objectives: (1) to study and evaluate clinical activities to improve

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effectiveness and efficiency; (2) to work for the implementation of proven changes in clinical activities (3) to encourage and support similar work throughout Scotland; and (4) to train National Health Services staff in Scotland in the principles and practice of health services research. Publication(s): Publications arising from HSRU research include: Postnatal Care--Time for Change; Cystic Fibrosis Carrier Screening; and The Process and Acceptability of Integrated Care for Asthma in General Practice. Unit publications submitted for peer review include: Medical versus Surgical Termination of Pregnancy and Hormone Replacement Therapy: Compliance and Cost After Screening for Osteoporosis. Other reviewed HSRU publications include: The Cost-effectiveness of Prophylaxis to Prevent Infective Endocarditis in Dental Practice and Caesarian Section Audit by Peer Review. Unit reports are: Day Surgery Practice in Scotland; Operation of Shared Care Schemes: a Postal Survey of Scotland and North West Thames Regional Health Authority, England; and Acute Medical Receiving in Aberdeen. Occasional papers and student reports are also available. HSRU unit reports and occasional papers are available to the public free of charge; most publications are published in various peer-reviewed journals. ·

International Association of Cystic Fibrosis Adults Address: International Association of Cystic Fibrosis Adults 82 Ayer Road, Harvard, MA 01451-1409 Telephone: (978) 456-838 Fax: (978) 456-8387 Email: [email protected] Web Site: http://www.ourworld.compuserve.com/homepages/fantognini/iacfa.h tm Background: The International Association of Cystic Fibrosis Adults (IACFA) is a nonprofit organization that provides information and support to individuals over the age of 18 who are diagnosed with cystic fibrosis, their families, allied health workers, and medical professionals. Cystic fibrosis (CF) is a rare inherited disorder that affects many exocrine ('outward-secreting') glands of the body including the sweat glands, salivary glands, and those within the pancreas and respiratory system. Due to unusually thick secretions of mucus that clog and obstruct air passages of the lungs, affected individuals experience chronic coughing and an increased susceptibility to repeated lung infections. Individuals with CF also exhibit an inability to break down food and absorb fats and nutrients properly; have abnormally salty sweat containing elevated

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levels of chloride and sodium; and/or may demonstrate other abnormalities. IACFA was established in 1982 and its mission is to assist in improving the quality of life by identifying common problems, attempting to define possible solutions, and enhancing the exchange of information in the world community of CF. The Association also endeavors to cooperate with the CF community in defining the new needs arising in the treatment of adults with CF and in raising the awareness of the medical profession to adults with CF as having specific requirements. IACFA publishes a quarterly self-titled newsletter and, every two years, sponsors an international conference open to adults with cystic fibrosis and their partners and siblings. The Association also maintains a site on the World Wide Web at http://www.ourworld.compuserve.com/homepages/fantognini/iacfa.h tm. Relevant area(s) of interest: Cystic Fibrosis, Fibrocystic Disease of Pancreas, Mucosis, Mucoviscidosis, Pancreatic Fibrosis ·

International Cystic Fibrosis Association Address: 323 Lippens Avenue Montreal, Quebec H2M 1H7, Canada Telephone: (514) 381-0922 Fax: (514) 381-8283 Web Site: http://www.iacfa.org/home.htm Background: The purpose and direction is to assist in improving the quality of life by identifying common problems, attempting to define possible solutions, and enhancing the exchange of information within the world community of adults with CF. They cooperate, whenever possible, with the CF community in defining the new needs arising in the treatment of adults with cystic fibrosis, and in raising the awareness of the medical profession to adults as a new challenge separate and apart from children with CF. Adults with cystic fibrosis are able to provide unique insights into common problems and potential solutions related to the disorder. Relevant area(s) of interest: Cystic Fibrosis

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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

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Email: [email protected] Web Site: http://www.modimes.org 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. Relevant area(s) of interest: Cystic Fibrosis ·

Maryland Advisory Council on Hereditary Disorders Maryland Department of Health and Mental Hygiene Office of the Secretary Address: 201 West Preston Street Baltimore, MD 21201 Telephone: (410) 767-6566 Fax: (410) 767-6489 Web Site: http://www.dhmh.state.md.us/ Background: The Maryland Advisory Council on Heredity Disorders was created by the State legislature to advise the Department of Health and Mental Hygiene about policy decisions for programs for the detection and management of hereditary disorders. Interests of the Council include sickle cell anemia, cystic fibrosis, hemophilia, Tay-Sachs disease, retinitis pigmentosa, muscular dystrophy, Cooley's anemia, Huntington's disease, and phenylketonuria. The Council answers inquiries, provides reference service and information on research in progress, distributes publications, and makes referrals to other sources of information. Services are free, except for bulk copies of publications, and available to anyone. Publication(s): Understanding Heredity Disorders; annual report; technical reports; data compilations. Relevant area(s) of interest: Cooley's anemia; Cystic fibrosis; Hemophilia; Hereditary diseases; Huntington's disease; Muscular dystrophy; Phenylketonuria; Retinitis pigmentosa; Sickle cell anemia; Tay-Sachs disease

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Michigan State University Human Genetics Address: Michigan State University Human Genetics MSU College of Human Medicine, B245 Life Sciences Building, East Lansing, MI 488241317 Telephone: (517) 353-2030 Fax: (517) 353-8464 Email: [email protected] Web Site: http://www.phd.msu.edu Background: Michigan State University (MSU) Human Genetics, is a service and research organization affiliated with the Department of Pediatrics/Human Development, Michigan State University College of Human Medicine. It is dedicated to providing diagnostic evaluation and prenatal diagnosis to individuals and families affected by genetic conditions, malformations, metabolic disease, malformation syndromes, or conditions resulting from exposure to human teratogens. A teratogen is any agent or factor that causes or increases the incidence of a congenital abnormality in a developing fetus. Established in 1975, the organization provides counseling and cytogenetic (chromosomal) and DNA diagnostic evaluations. The DNA diagnostic laboratory is prepared to identify both homozygous affected individuals as well as carriers for genetic diseases, such as cystic fibrosis. MSU's Human Genetics provides genetics counseling, referrals to prenatal support groups, and teratogen counseling utilizing the REPROTOX database. Michigan State University Human Genetics offers interested individuals a variety of guides, brochures, and pamphlets discussing genetics clinics and diagnostic counseling services; prenatal diganosis and reproductive genetics; and testing and risk assessment specifically for cystic fibrosis. Relevant area(s) of interest: Cystic Fibrosis

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National Institute of Diabetes and Digestive and Kidney Diseases Address: 31 Center Drive, MSC-2560 Bethesda, MD 20892-2560 Building 31, Room 9A-04 Office of Communications and Public Liaison Telephone: (301) 496-3583 Fax: (301) 496-7422 Web Site: http://www.niddk.nih.gov/ Background: The National Institute of Diabetes and Digestive and Kidney Diseases conducts and supports research on many of the most serious diseases affecting public health. The Institute supports much of the clinical research on the diseases of internal medicine and related

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subspecialty fields as well as many basic science disciplines. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) responds to inquiries from consumers and professionals, disseminates information and publications, and conducts and supports research on diabetes, digestive disorders, endocrine disorders, and kidney diseases. Some materials are available in Spanish. Relevant area(s) of interest: Cystic fibrosis; Diabetes mellitus; Digestive system diseases; Endocrine disorders; Kidney diseases; Medical research; Metabolic diseases ·

National Jewish Medical and Research Center Address: 1400 Jackson St. Denver, CO 80206 Telephone: (303) 388-4461; (800) 222-5864 (Toll-free) Email: [email protected] Web Site: http://www.nationaljewish.org Background: The National Jewish Medical and Research Center, formerly the National Jewish Center for Immunology and Respiratory Medicine, was founded around the turn of the century to care for the victims of tuberculosis. The Hospital provided treatment for victims, while the Denver Sheltering Home (the Center's forerunner) provided care for children of victims. The two institutions merged in 1978 and now constitute the largest U.S. medical center devoted to the study and treatment of chronic respiratory diseases and immune system disorders, including asthma, emphysema, tuberculosis, chronic bronchitis, interstitial lung disease, juvenile rheumatoid arthritis, and lupus. Research activities cover an ever-broadening range of both basic and applied science, from examination of basic life processes to in-depth clinical studies of particular diseases. The Center provides an information service called LUNGLINE, (800)222-LUNG, for individuals with questions about lung diseases and allergies. Beyond the areas of study and treatment listed, LUNGLINE offers information on pneumonia, sarcoidosis, smoking, asbestosis, cystic fibrosis, occupational lung diseases, and other topics. Professional staff publish scientific papers and participate in seminars and conferences. In addition, the Center conducts a formal medical and research fellowship program to train young physicians and researchers in the latest methods of investigating and controlling these illnesses. Relevant area(s) of interest: Asthma; Chronic obstructive lung disease; Cystic fibrosis; Emphysema; Environmental irritants; Immunology; Lung diseases; Pulmonary fibrosis; Rheumatoid diseases; Sarcoidosis; Smoking; Tuberculosis

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National Kidney Foundation Address: National Kidney Foundation 30 East 33rd Street, New York, NY 10016 Telephone: (212) 889-2210 Toll-free: (800) 622-9010 Fax: (212) 689-9261 Web Site: http://www.kidney.org Background: Established in 1950, the National Kidney Foundation is a voluntary not-for-profit organization dedicated to preventing kidney and urinary tract diseases, improving the health and well-being of individuals and families affected by these diseases, and increasing the availability of organs for transplantation. The Foundation is committed to gaining adequate support for research and research training; fostering continuing education of health care professionals; expanding and developing patient services and community resources; increasing public awareness of kidney diseases; monitoring health policy development; and increasing fund-raising for new programs and research. In addition, the Foundation supports and promotes medical research into the causes, prevention, and treatment of kidney diseases. A wide variety of educational materials is produced and distributed by the Foundation. These materials are listed in a booklet entitled Public and Professional Education Materials.

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Second Wind Lung Transplant Association, Inc Address: Second Wind Lung Transplant Association, Inc. 300 South Duncan Avenue, Suite 227, Clearwater, FL 33755 Telephone: (517) 353-2030 Toll-free: (888) 222-2690 Fax: (727) 442- 9762 Email: [email protected] Web Site: http://www.2ndwind.org Background: Second Wind Lung Transplant Association, Inc. is a not-forprofit organization dedicated to improving the quality of life for lung transplant recipients, lung surgery candidates, people with related pulmonary concerns, and their families. The Association provides support, advocacy, education, information, and guidance through a spirit of service, 'adding years to their lives and life to their years.' Established in 1995 by a group of lung transplant recipients, candidates, and their families, Second Wind has quarterly support group meetings to provide educational programs (e.g., on nutrition, effects of medications and exercise, physical therapy) for both lung transplant candidates and recipients; to share experiences; and to enjoy social activities. Second

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Wind also is developing a directory of candidates and lung transplant recipients to provide networking opportunities; is establishing a mentor program to offer fellowship to affected individuals and families during the transplant experience; and is planning to establish low-cost Lung Transplant Housing near transplant hospitals for use by candidate and recipient transplant affected individuals and their support person. In addition, the organization provides educational programs; seeks to increase Organ Donor Awareness; and provides a quarterly newsletter entitled 'AirWays' to their members. The Second Wind Lung Transplant Association also has a web site on the Internet that provides information to individuals who seek information on lung transplantation. The site also provides linkage to information on certain specific pulmonary disorders; describes Second Wind's mentoring program; and provides information concerning financing lung transplantation. Such information includes listings of organizations that may provide advocacy, assistance with fund-raising, financial grants, and/or medication or pharmaceutical payment assistance grants or programs. Relevant area(s) of interest: Cystic Fibrosis

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 parent 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 cystic fibrosis. 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

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government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov. Simply type in “cystic fibrosis” (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 “cystic fibrosis”. 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 “cystic fibrosis” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with cystic fibrosis. 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 medical conditions. 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 “cystic fibrosis” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms to discuss different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online 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 child’s doctor or other healthcare providers, as the treatments or discoveries you hear about may

Seeking Guidance 53

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

International Cystic Fibrosis Support Group http://cf.conncoll.edu/

·

CF Support Groups http://www.cf-web.org/support.html

·

Cystic Fibrosis Resources for Daily Living and Information http://www.cysticfibrosis.com/

Finding Doctors All parents must go through the process of selecting a physician for their children with cystic fibrosis. While this process will vary, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:10 ·

If your child is 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 child’s doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to

10

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

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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 11 http://www.abms.org/newsearch.asp. 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 medical conditions. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Doctor12 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your child’s health insurance plan and if he or she is taking new patients. If the doctor is not covered by your child’s plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your first choice. During the first visit you will have the opportunity to evaluate your child’s doctor and to find out if your child feels comfortable with him or her.

Working with Your Child’s Doctor13 Research has shown that parents who have good relationships with their children’s doctors tend to be more satisfied with their children’s care. Here are some tips to help you and your child’s doctor become partners:

11 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. 12 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 13 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 55

·

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

·

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

·

Tell your doctor about any natural or alternative medicines your child is taking.

·

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

·

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

·

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

·

Ask the doctor to draw pictures if you think that this will help you and your child understand.

·

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

·

Take information home. Ask for written instructions. Your child’s doctor may also have brochures and audio and videotapes on cystic fibrosis.

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

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help parents find healthcare professionals. These include:14 ·

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.

14

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Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Bronchitis: Inflammation of one or more bronchi. [EU] Contraception: The prevention of conception or impregnation. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Dysplasia: Abnormal development or growth. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Emphysema: Chronic lung disease in which there is permanent destruction of alveoli. [NIH] 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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] 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] Exocrine: 1. secreting outwardly, via a duct;. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and

Seeking Guidance 57

intestine, as a gastrointestinal fistula. [EU] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hepatic: Pertaining to the liver. [EU] Hepatitis: Inflammation of the liver. [EU] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [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] Inhalation: The drawing of air or other substances into the lungs. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] 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

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the spinal axis, as the neutral arch. [EU] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Pathogenesis: The cellular events and reactions that occur in the development of 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] Porphyria: A pathological state in man and some lower animals that is often due to genetic factors, is characterized by abnormalities of porphyrin metabolism, and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Prophylaxis: The prevention of disease; preventive treatment. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Rheumatoid: Resembling rheumatism. [EU] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Surgical: Of, pertaining to, or correctable by surgery. [EU] Teratogens: An agent that causes the production of physical defects in the developing embryo. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH] Ventilation: The process of exchange of air between the lungs and the atmosphere leading to exchange of gases in the blood. [NIH]

Clinical Trials 59

CHAPTER 3. CLINICAL TRIALS AND CYSTIC FIBROSIS Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your child’s 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 cystic fibrosis.

What Is a Clinical Trial?15 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 cystic fibrosis 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.

15

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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 cystic fibrosis.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for cystic fibrosis 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 child’s visits. All doctors and researchers who take part in the study on cystic fibrosis carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat your child 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 cystic fibrosis. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This

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treatment, like a placebo, has no effect on cystic fibrosis and will not harm your child. 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 have your child participate in a clinical trial, you will not know which group he or she will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request that your child receive the new treatment instead of the placebo or “sham” treatment. Often, you will not know until the study is over whether your child has 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 participants 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 cystic fibrosis 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 cystic fibrosis. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a medical condition develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a medical condition usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Your Child in a Clinical Trial? Not everyone can take part in a clinical trial for a specific medical condition. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of the condition, as well as, the age and previous treatment history of the patient. You or your child’s doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you would like your child to participate in a clinical trial, your child’s doctor must contact one of the trial’s investigators and provide details about his or her diagnosis and medical history.

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When participating in a clinical trial, your child may be required to have a number of medical tests. Your child may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, your child may be required to receive inpatient hospital care. He or she may have to return to the medical facility for followup 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 Cystic Fibrosis The National Institutes of Health and other organizations sponsor trials on various medical conditions. 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 medical condition at all times. The following lists recent trials dedicated to cystic fibrosis.16 If the trial listed by the NIH is still recruiting, your child 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 child’s physician who can help you determine if your child might benefit from participation. ·

8-Day Safety, Tolerability, and Effects Study of Inhaled INS37217 and Placebo In Adult and Pediatric Cystic Fibrosis Patients Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): Inspire Pharmaceuticals Purpose - Excerpt: The purpose of this ascending dose group study is to assess the safety, tolerability, and effects of multiple dose levels of INS37217 and placebo followed by five days twice daily treatment with maximum tolerated dose administered by inhalation via the Pari LC Star nebulizer in adult and pediatric patients with cystic fibrosis Phase(s): Phase I; Phase II Study Type: Interventional

16

These are listed at www.ClinicalTrials.gov.

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00034515 ·

A Pilot Trial of Phenylbutyrate/Genistein Duotherapy (for Cystic Fibrosis) Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Cystic Fibrosis Foundation Therapeutics Purpose - Excerpt: We are testing a new combination of medicines, to determine if they could be used to treat cystic fibrosis (CF). Subjects with CF who have two copies of the most common mutation (change) found in patients with CF called DF508. CF is caused by a lack of chloride movement in the nose, sinuses, lungs, intestines, pancreas and sweat glands. We are conducting this study to determine the safety of using a combination of two medicines, Phenylbutyrate and Genistein, to improve the ability of the cells lining the nose to regulate movement of salt (chloride) and water in people with CF. Phenylbutyrate has been extensively used to treat patients with rare metabolic diseases (which are very different from CF), Phenylbutyrate is an investigational drug for the purpose of this study. Genistein is a naturally occurring substance that is found in food products such as soy and tofu, but is also an investigational drug for this study. Both drugs may be able to restore normal chloride movements in body organs and glands. We will be studying salt and water in the nose movement by a technique called nasal transepithelial potential difference (NPD). Phase(s): Phase I Study Type: Interventional Contact(s): Pennsylvania; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19101, United States; Recruiting; Ronald C Rubenstein, M.D., Ph.D. 215-590-1281; Regina Healy 215-590-7185 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00016744

·

A Study of the Safety and Efficacy of Tobramycin for Inhalation in Young Children with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Research Resources (NCRR)

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Purpose - Excerpt: This study's primary goals are to test the safety and effectiveness of Tobramycin for Inhalation (TOBIr) in cystic fibrosis (CF) patients who are between 6 months and 6 years of age. This drug is an antibiotic that is inhaled into the lungs by the patient. It has already been studied and approved by the FDA for treatment of CF patients 6 years and older. Lung fluid will be examined for bacteria before and after the 28-day treatment. The amount of bacteria before and after treatment will be compared. This will indicate whether the antibiotic was effective in killing bacteria in the lungs. Once treatment begins, patients will be monitored every 2 weeks throughout the study (5 exams in 56 days). Half of the patients will receive TOBIr, half will receive a placebo (a substance that looks like TOBIr but contains no medication). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00006280 ·

Bone Health of People with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Cystic Fibrosis Foundation Purpose - Excerpt: People with cystic fibrosis (CF) now frequently live into adulthood and with this extended life expectancy has come new clinical problems. Poor bone health, including osteoporosis and bone fractures, is one of these increasingly important conditions. Preventing the negative outcomes of poor bone health in later life is primarily related to ensuring optimal growth (weight and height) and obtaining maximal amount of bone mass during growth and development. This study will identify factors that influence bone health in a sample of children, adolescents and young adults as measured by dual energy x-ray absorptiometry and new bone densitometry methods (peripheral quantitative computerized tomography [p-QCT] and bone sonometer). We will also identify factors which influence changes in bone status over a 12-month follow-up period in a subsample of people with CF. Study Type: Observational Contact(s): Pennsylvania; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States; Recruiting; Rita M. Herskovitz, M.S., R.D. 215-590-7174; Virginia A. Stallings, M.D., Principal Investigator

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Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00008762 ·

Growth Hormone Use in Cystic Fibrosis - a Multicenter Study Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Genentech Purpose - Excerpt: Cystic Fibrosis (CF) is the most common lethal genetic disorder in America. Previous studies by our group and others have shown that human recombinant growth hormone (GH) improves height velocity, weight velocity, lean body mass (LBM) and pulmonary function. These positive results have prompted us to ask further questions regarding GH use in CF including: a) Do patients with better baseline body weight and pulmonary function derive more benefit from treatment than those with worse weight and pulmonary function?, b) Does GH use improve the patient's quality of life?, c) Once GH is discontinued, are the positive effects sustained? We hypothesize that GH treatment in CF patients will improve their clinical status and their quality of life. We further hypothesize that these effects will be present regardless of baseline body weight or pulmonary function, and that positive outcome will be sustained for at least one year after GH treatment is discontinued. To test our hypothesis, we will recruit 40 prepubertal children from five CF centers across the United States (8 per center). Patients will be randomly assigned to receive treatment with GH (0.3mg/kg/wk) during either the first or the second year. All subjects will be seen every three months. We will evaluate the following parameters every three months: 1) height, height velocity and Z-score, 2) body weight and weight velocity. Every six months we will measure: 1) lean body mass utilizing DEXA, 2) pulmonary function, including measurement of respiratory muscle strength (peak inspiratory and peak expiratory pressure), 3) quality of life (QOL), quantitated from QOL forms specific for CF ("The Cystic Fibrosis Questionnaire"). After one year of study, subjects will "cross-over" to the other treatment arm. This 24 month study will allow us to statistically compare outcome measures in 20 treated and 20 nontreated subjects from multiple centers, and will allow us to assess sustained effect in the 20 subjects who receive GH during the first year, by comparing their results to results obtained during the year post treatment. Phase(s): Phase III Study Type: Interventional Contact(s): Julie Rice, R.N. 1-801-585-9837; Texas; University of Texas Medical School, Houston, Texas, 77030, United States; Recruiting; Julie

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Rice, R.N. 713-500-5646; Utah; University of Utah, Dept of Pediatric Endocrinology, Salt Lake City, Utah, 84132, United States; Recruiting. Study chairs or principal investigators: Dana Hardin, M.D., Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00005112 ·

Phase II Study of Growth Hormone in Children With Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): University of Utah Purpose - Excerpt: Objectives: I. Determine the effect of growth hormone on height, height velocity, body weight, and lean body mass in patients with cystic fibrosis. II. Determine the effect of growth hormone on pulmonary function in these patients. III. Determine the impact of this drug on the quality of life in these patients. IV. Determine if the clinical response from this drug is sustained in these patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00016445

·

Randomized Study of Alendronate in Adult Patients With Cystic Fibrosis Related Osteoporosis Condition(s): Osteoporosis; Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; University of North Carolina Purpose - Excerpt: Objectives: I. Determine the bioavailability and biologic effect of alendronate on bone metabolism in patients with cystic fibrosis. II. Assess the safety and efficacy of this treatment regimen in improving osteoporosis in this patient population. Study Type: Interventional Contact(s): North Carolina; University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599-7070, United States; Recruiting; Robert Aris 919-966-2531. Study chairs or principal investigators: Robert Aris, Study Chair; University of North Carolina Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004489

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·

Role of Genetic Factors in the Development of Lung Disease Condition(s): Alpha 1 Antitrypsin Deficiency; Cystic Fibrosis; Lung Disease; Obstructive Lung Disease; Sarcoidosis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease. The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers. Study Type: Observational Contact(s): Maryland; National Heart, Lung and Blood Institute (NHLBI), 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/w2r/show/NCT00001532

·

Role of Toxins in Lung Infections Caused by Pseudomonas Aeruginosa Condition(s): Pseudomonas Infection; Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Some bacteria that cause disease can produce toxic substances that may worsen the disease. Pseudomonas aeruginosa is a bacteria that can produce a variety of toxins and is of special interest for patients with cystic fibrosis and repeated long term lung infections. The goal of this study is to determine whether specific toxins produced by Pseudomonas aeruginosa may be important in the disease process of chronic lung infections of patients with cystic fibrosis. This study will attempt to measure bacterial production of toxins in blood and sputum and immune system response to toxins in the blood. Researchers plan to study 4 effector proteins (toxins). 1. exotoxin A 2. Exo S 3. Exo U 4. Pcr V Study Type: Observational Contact(s): Maryland; National Heart, Lung and Blood Institute (NHLBI), 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/w2r/show/NCT00027183

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·

Study of Hepatic Glucose Production and De novo Lipogenesis in Patients With Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): University of Utah Purpose - Excerpt: Objectives: I. Determine the amount of hepatic glucose production derived from gluconeogenesis and glycogenolysis in the postabsorptive state in patients with cystic fibrosis. II. Determine de novo lipogenesis in relationship to resting energy expenditure in this patient population. Study Type: Observational Contact(s): Utah; University of Utah School of Medicine, Salt Lake City, Utah, 84132, United States; Recruiting; Dana S. Hardin 801-585-3485. Study chairs or principal investigators: Dana S. Hardin, Study Chair; University of Utah Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00014781

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Study of Mycobacterial Infections Condition(s): Atypical Mycobacterium Infections; Cystic Fibrosis; Job's Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the symptoms, course of disease and treatment of non-tuberculous mycobacterial (NTM) infections, as well as the genetics involved in these infections. Patients with NTM have recurrent lung infections and sometimes infections of the skin and other organs as well. They may also have curvature of the spine, barrel chest, and heart valve weakness. The study will compare the features of NTM with those of Job syndrome and cystic fibrosis, other diseases involving recurrent infections of the lungs and possibly other organs. Patients with diagnosed or suspected non-tuberculous mycobacterial infection, cystic fibrosis or Job syndrome may be eligible for this study. All participants will have a medical and family history, blood and urine tests, imaging studies that may include X-rays, computed tomography (CT) or magnetic resonance imaging (MRI) scans, and DNA and other genetic studies. In addition, all patients with Job syndrome and cystic fibrosis, and patients with NTM who have lung disease undergo the following procedures: - Scoliosis survey - X-rays of the spine to look for curvature or other abnormalities of the spinal column - Echocardiography - imaging test that uses sound waves to

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examine the heart chambers and valves - Electrocardiogram measurement of the electrical activity of the heart - Pulmonary function tests - breathing tests to measure how much air the patient can move into and out of the lungs - Body measurements - measurements of height, weight, arm span, finger length, etc. - Joint function - assessment of joint mobility using different maneuvers to test flexibility of joints and ligaments - Examination of physical features that might be associated with NTM, such as high arched palate of the mouth, flat feet, or certain skin features - Dermatology (skin) examination for reactive skin conditions or other skin problems and possibly a skin biopsy (surgical removal of a small skin tissue sample for microscopic examination) Interview with genetics specialist These tests may require several days to complete. Patients with NTM will also be examined by a cystic fibrosis specialist and may have a sweat test. In addition, NTM patients will be asked to return to NIH every year for 5 years for follow-up tests, if medically indicated, including CT of the chest, scoliosis survey and examination by other specialists. Study Type: Observational Contact(s): Maryland; National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00018044 ·

Study of Tauroursodeoxycholic Acid for Hepatobiliary Disease in Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Children's Hospital Medical Center - Cincinnati Purpose - Excerpt: Objectives: I. Determine the optimum dose of tauroursodeoxycholic acid (TUDCA) required to achieve maximal bioavailability for patients with cystic fibrosis-associated liver disease. II. Compare optimized doses of TUDCA with ursodiol (ursodeoxycholic acid; UDCA) for effects on biliary bile acid composition and metabolism, serum biochemistries, fat absorption, and fat-soluble vitamin status in these patients. Study Type: Interventional Contact(s): Italy; University of Milan, Milan, 20122, Italy; Recruiting; Carla Colombo 2-8-912-9975; Colorado; Children's Hospital of Denver,

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Denver, Colorado, 80218, United States; Recruiting; Michael Narkowicz 303-861-6669; Ohio; Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio, 45229-3039, United States; Recruiting; Kenneth Setchell 513-636-4548. Study chairs or principal investigators: Kenneth Setchell, Study Chair; Children's Hospital Medical Center - Cincinnati Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004441 ·

Study of Total Energy Expenditure in Infants and Children With Moderate to Severe Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Indiana University Purpose - Excerpt: Objectives: I. Compare the resting energy expenditure using respiratory calorimetry in infants and children with moderate to severe cystic fibrosis versus age matched healthy controls. II. Determine the total energy expenditure and energy spent on physical activity using the doubly labeled water method in these patient populations. Study Type: Observational Contact(s): Indiana; Indiana University, Indianapolis, Indiana, 462025167, United States; Recruiting; Catherine A. Leitch 317-274-4920. Study chairs or principal investigators: Catherine A. Leitch, Study Chair; Indiana University Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00006273

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Studying Patients with Cystic Fibrosis and Other Pulmonary and Pancreatic Disorders Condition(s): Bronchiectasis; Cystic Fibrosis; Pancreatic Insufficiency Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Cystic fibrosis is a disease that affects many parts of the body, particularly the lungs and pancreas. The main purpose of this study is to further understand the natural history, clinical presentation, and genetics of cystic fibrosis. Patients with cystic fibrosis will be asked to participate in this study by undergoing standard medical tests and procedures. Patients will have a history taken and have a physical examination as well as blood tests, and a sweat test (a test for cystic fibrosis of the pancreas in which electrolytes are measured in collected

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sweat). Patients may also be asked to provide samples of urine, stool, and sputum for additional tests. More complicated procedures such as bronchoscopy or bronchoalveolar lavage may be required for diagnosis, treatment, or research purposes. Patients will receive appropriate treatment with antibiotics, pancreatic enzymes, vitamins, physiotherapy, and other agents. Medications may be given by mouth or injected into a vein. This study will provide patients with information on the prognosis of the disease as well as recommendations for management of cystic fibrosis. In addition this study will provide information to researchers which may be useful in other studies of cystic fibrosis. 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/w2r/show/NCT00001223 ·

Tissue Collection Protocol for Individuals with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Lungs of individuals with cystic fibrosis (CF) are frequently colonized with a number of bacterial pathogens. One of the most common organisms is Pseudomonas aeruginosa. Previous studies have shown the presence of the type III-secretion pathway within P. aeruginosa, implicating these cytotoxins as virulence factors for this organism. To evaluate further the effect of these cytotoxins on lung cells, we would like to collect plasma and tissue from individuals with CF. Because larger quantities of plasma than can safely be obtained by simple phlebotomy will be required, apheresis procedures performed in the Clinical Center Apheresis Unit will be used. To obtain lung cells from patients with CF infected with P. aeruginosa, tissue from explanted lungs will be collected in collaboration with INOVA Fairfax Hospital. We intend to look for expression of the type- III proteins of P. aeruginosa by measuring the immune response against components of the type- III pathway and their presence in lung cells. Study Type: Observational Contact(s): Maryland; National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting;

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Patient Recruitment and Public Liaison [email protected]; TTY 1-866-411-1010

Office

1-800-411-1222

Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00015756 ·

Benefits and Risks of Newborn Screening for Cystic Fibrosis Condition(s): Cystic Fibrosis; Lung Disease; Pseudomonas Infections Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Research Resources (NCRR) Purpose - Excerpt: Although cystic fibrosis (CF) is the most common, lifethreatening autosomal recessive genetic disorder of the white population, there are often delays in diagnosis and hence start of treatment. Advances of the past two decades have made CF screening feasible using routinely collected neonatal blood specimens and measuring an enzyme level followed by CF mutation DNA analysis. Our overall goal of the study is to see if early diagnosis of CF through neonatal screening will be medically beneficial without major risks. ''Medically beneficial'' refers to better nutrition and/or pulmonary status, whereas '' risks'' include laboratory errors, miscommunication or misunderstanding, and adverse psychosocial consequences. Specific aims include assessment of the benefits, risks, costs, quality of life, and cognitive function associated with CF neonatal screening and a better understanding of the epidemiology of CF. A comprehensive, randomized clinical trial emphasizing early diagnosis as the key variable has been underway since 1985. Nutritional status has been assessed using height and weight measurements and biochemical methods. The results have demonstrated significant benefits in the screened (early diagnosis) group. We are now focusing on the effect of early diagnosis of CF on pulmonary outcome. Pulmonary status is measured using chest radiographs, chest scans using high resolution computerized tomography, and pulmonary function tests. Other factors that we are looking at include risk factors for the acquisition of respiratory pathogens such as Pseudomonas aeruginosa, quality of life and cognitive function of children with CF who underwent early versus delayed diagnosis, as well as the cost effectiveness of screening and the costs of diagnosis and treatment of CF throughout childhood. If the questions underlying this study are answered favorably, it is likely that neonatal screening using a combination of enzyme level (immunoreactive trypsinogen) and DNA test will become the routine method for identifying new cases of CF not only in the State of Wisconsin, but throughout the country. Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00014950 ·

Phase I Pilot Study of Gene Therapy for Cystic Fibrosis Using Cationic Liposome Mediated Gene Transfer Condition(s): Cystic Fibrosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Alabama Purpose - Excerpt: Objectives: Determine whether copies of the cystic fibrosis gene (pGT-1) can be delivered to the cells lining the nose of cystic fibrosis patients using cationic liposome (DMRIE/DOPE) mediated gene transfer. Phase(s): Phase I Study Type: Interventional Contact(s): Eric J. Sorscher 205-934-9640. Study chairs or principal investigators: Eric J. Sorscher, Study Chair; University of Alabama Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004471

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Phase I Randomized Study of Adeno-Associated Virus-CFTR Vector in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Florida Purpose - Excerpt: Objectives: I. Determine the maximum tolerated dose of recombinant adeno-associated virus-CFTR vector in patients with cystic fibrosis. II. Assess the safety of this gene therapy in these patients. III. Assess the in vivo gene transfer of this vector in these patients. IV. Assess the CFTR gene expression and physiologic activity following gene transfer in these patients. V. Assess the clinical impact of CFTR gene expression following gene transfer in these patients. VI. Monitor patient immune response directed against CFTR or vector components following vector administration. Phase(s): Phase I Study Type: Interventional Contact(s): Terence Flotte 352-846-2739. Study chairs or principal investigators: Terence Flotte, Study Chair; University of Florida

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Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004533 ·

Phase II Pilot Study to Compare the Bioavailability of Buffered, Enteric-Coated Ursodiol with Unmodified Ursodiol for Chronic Cholestatic Liver Disease and Cystic Fibrosis-Associated Liver Disease Condition(s): Cystic Fibrosis; Gastrointestinal Diseases; Cholestasis Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Children's Hospital Medical Center - Cincinnati Purpose - Excerpt: Objectives: I. Compare the bioavailability of polymercoated and buffered ursodiol (ursodeoxycholic acid) to unmodified ursodiol in patients with cystic fibrosis-associated liver disease or chronic cholestatic liver disease. II. Compare the differences in pruritus, weight gain, and liver function for both treatments. Phase(s): Phase II Study Type: Interventional Contact(s): Ohio; Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio, 45229-3039, United States; William Balistreri 513-6364415. Study chairs or principal investigators: William Balistreri, Study Chair; Children's Hospital Medical Center - Cincinnati Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004315

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Weight Gain in CF Condition(s): Cystic Fibrosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The current study examines the efficacy of two treatments to help children with cystic fibrosis (CF) meet their dietary calorie requirements of 120% to 150% of the recommended daily allowance of energy and the effect of these treatments on weight gain and maintenance. One treatment provides children with CF and their parents nutrition education about the best foods for meeting their dietary needs. The second treatment gives children with CF and their families similar nutritional information plus behavioral parenting methods for motivating children to eat the recommended foods. Children with CF and their families are seen weekly for 7 treatment sessions across 9 weeks for the active phase of treatment. Families are then followed for 2 years after treatment in order to better understand how long the treatments are

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effective and to determine the health benefits of better nutrition status and weight gain. Phase(s): Phase III Study Type: Interventional Contact(s): Florida; University of Florida, Gainesville, Florida, 32601, United States; Alexander Quittner; Ohio; Children's Hospital Medical Center, Cincinnati, Cincinnati, Ohio, 45229, United States; Lori J. Stark 513-636-7727 [email protected]. Study chairs or principal investigators: Lori Stark, Principal Investigator; Children's Hospital Medical Center Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00006169 ·

A multi-centered study of the long-term effect of salmeterol and albuterol in cystic fibrosis Condition(s): Cystic Fibrosis Study Status: This study is suspended. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Long term use of bronchodilators in CF is beneficial to the improvement of pulmonary function and symptoms. This study is investigating the long-term benefit of administration of the drug Salmeterol, a bronchodilator. Salmeterol will be compared to albuterol or placebo. The medication will be inhaled twice a day for 6 months. Study Type: Interventional Contact(s): Steve Shapiro, M.D. 1-314-454-2694; Missouri; Division of Allergy and Pulmonary Medicine, St. Louis, Missouri, 63110, United States; Steve Shapiro, MD 314-454-2694 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00005110

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Multicenter Study of Nontuberculous Mycobacteria in Cystic Fibrosis Patients Condition(s): Cystic Fibrosis; Atypical Mycobacterium Infection Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of North Carolina Purpose - Excerpt: Objectives: I. Determine the prevalence of nontuberculous mycobacteria in sputum cultures from patients with cystic fibrosis. II. Compare the clinical course of patients with negative versus positive cultures.

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Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004296 ·

Phase I Pilot Study of Ad5-CB-CFTR, an Adenovirus Vector Containing the Cystic Fibrosis Transmembrane Conductance Regulator Gene, in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of North Carolina Purpose - Excerpt: Objectives: I. Assess the safety and efficacy of gene transfer into the nasal epithelium using Ad5-CB-CFTR, an E1-deleted adenovirus vector containing the cystic fibrosis transmembrane conductance regulator gene, in patients with cystic fibrosis (CF). II. Determine whether ion transport abnormalities in CF airway cells can be corrected. Phase(s): Phase I Study Type: Interventional Contact(s):. Study chairs or principal investigators: Michael R. Knowles, Study Chair; University of North Carolina Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004779

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Phase I Randomized Study of CPX for the Treatment of Adult Patients with Mild Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development; SciClone Pharmaceuticals Purpose - Excerpt: Objectives: I. Evaluate the safety of ascending doses of CPX administered to adult patients with mild cystic fibrosis. II. Evaluate the pharmacokinetics of ascending doses of CPX in this patient population. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004428

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Phase I Study of Liposome-Mediated Gene Transfer in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Alabama Purpose - Excerpt: Objectives: Evaluate the efficacy and safety of lipidmediated transfer of the cystic fibrosis transmembrane conductance regulator gene to nasal epithelium in patients with cystic fibrosis. Phase(s): Phase I Study Type: Interventional Contact(s):. Study chairs or principal investigators: Eric J. Sorscher, Study Chair; University of Alabama Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004806

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Phase I Study of the Third Generation Adenovirus H5.001CBCFTR in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Pennsylvania Purpose - Excerpt: Objectives: I. Assess the safety and feasibility of gene transfer with the third generation adenovirus H5.001CBCFTR in patients with cystic fibrosis. Phase(s): Phase I Study Type: Interventional Contact(s):. Study chairs or principal investigators: James M. Wilson, Study Chair; University of Pennsylvania Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004287

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Phase II Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Mucoid Exopolysaccharide Pseudomonas Aeruginosa Immune Globulin for Cystic Fibrosis Condition(s): Cystic Fibrosis; Bacterial Infections Study Status: This study is completed.

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Sponsor(s): National Center for Research Resources (NCRR); Vanderbilt University Medical Center Purpose - Excerpt: Objectives: I. Assess the efficacy of monthly intravenous mucoid exopolysaccharide Pseudomonas aeruginosa immune globulin (MEP IGIV) given over 1 year in reducing the frequency of acute pulmonary exacerbation in patients with cystic fibrosis, mild to moderate pulmonary disease, and mucoid P. aeruginosa colonization. II. Assess the effect of MEP IGIV on FEV1, sputum density of mucoid P. aeruginosa, and the quality of life in these patients. III. Assess the safety of monthly MEP IGIV. IV. Assess population-based MEP IGIV pharmacokinetics during chronic therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004747 ·

Phase III Randomized Study of the Inhalation of Tobramycin in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis; Bacterial Infection Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of tobramycin in patients with cystic fibrosis who are chronically colonized with Pseudomonas aeruginosa. II. Determine whether this treatment produces tobramycin-resistant bacteria at a frequency different from the placebo group and whether the emergence of resistance is associated with a lack of clinical response. Phase(s): Phase III Study Type: Interventional Contact(s): Alan Bruce Montgomery 206-270-3326. Study chairs or principal investigators: Alan Bruce Montgomery, Study Chair; Pathogenesis Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004829

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Pressure support ventilation during CF exacerbations Condition(s): Cystic Fibrosis Study Status: This study is suspended.

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Sponsor(s): National Center for Research Resources (NCRR); Cystic Fibrosis Foundation Purpose - Excerpt: Chest physiotherapy is recognized as a mainstay of cystic fibrosis therapy, and is particularly important during treatment of pulmonary exacerbations. For some patients, especially those with moderate to severe compromise of lung function, this therapy may impose a high demand in the work of breathing and energy expenditure. The goal of this study is to evaluate the effectiveness of adding pressure support ventilation (PSV) during chest physiotherapy sessions in patients with cystic fibrosis with moderate to severe lung function compromise being treated for a pulmonary exacerbation. Study Type: Interventional Contact(s): Minnesota; University of Minnesota, Minneapolis, Minnesota, 55455, United States; Carlos Milla, M.D. 612-624-0962 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00008775 ·

Quantification of pulmonary neutrophil activity in cystic fibrosis using radiolabeled fluorodeoxyglucose and PET imaging Condition(s): Cystic Fibrosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: It has been shown that neutrophils (a specific type of cell) are involved in inflammation in the lungs of CF patients. Neutrophil levels in CF patients have been measured by bronchoalveolar lavage (BAL), which samples cells in the fluid lining of the lungs. Other studies have measured neutrophil levels and inflammation in other parts of the body using PET scanning. This study aims to show that PET scanning can be used as a non-invasive marker of inflammation in the lungs of patients with CF, which would be a useful tool in treatment. The primary goal of this study is to draw a connection between the level of inflammation shown in the PET scan and the number of neutrophils obtained from the BAL. This study will also look at how the PET images relate to inflammatory molecules in the lungs and to the FEV-1 obtained through spirometry. Study Type: Observational Contact(s): Missouri; Washington University School of Medicine, Saint Louis, Missouri, 63110, United States; Daniel P. Schuster, MD 314-3623776 [email protected]; Daniel P. Schuster, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00023465

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Randomized Study of Pancrelipase With Bicarbonate (PANCRECARB) Capsules in Reducing Steatorrhea in Patients With Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Indiana University School of Medicine Purpose - Excerpt: Objectives: I. Compare the efficacy of enteric coated pancrelipase with bicarbonate (PANCRECARB) capsules versus the patient's usual enteric coated pancreatic enzyme without bicarbonate in decreasing fecal fat and nitrogen losses in patients with cystic fibrosis. Study Type: Interventional Contact(s): Mary Sue Brady 317-274-9911. Study chairs or principal investigators: Mary Sue Brady, Study Chair; Indiana University School of Medicine Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00006063

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Study of Ibuprofen to Preserve Lung Function in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development; Case Western Reserve University Purpose - Excerpt: Objectives: I. Determine the effect of different doses of ibuprofen on neutrophil (polymorphonuclear leukocyte; PMN) delivery to a mucosal surface (the oral mucosa) in patients with cystic fibrosis and healthy controls. II. Determine the duration of effect (and possible rebound effect) of ibuprofen on PMN delivery to a mucosal surface in these patients. Study Type: Interventional Contact(s): Michael W Konstan 216-844-3267. Study chairs or principal investigators: Michael W Konstan, Study Chair; Case Western Reserve University Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004440

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Study of Metabolic Effects of Pregnancy in Women With Cystic Fibrosis Condition(s): Cystic Fibrosis

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Study Status: This study is terminated. Sponsor(s): National Center for Research Resources (NCRR); University of Utah Purpose - Excerpt: Objectives: I. Compare the clinical status of pregnant vs non-pregnant women with cystic fibrosis. II. Determine glucose tolerance during each trimester of pregnancy in these women. III. Evaluate peripheral insulin sensitivity in these women. IV. Evaluate whole body protein turnover and hepatic glucose production in these women. V. Determine resting energy expenditure in these women. Study Type: Observational Contact(s): Utah; University of Utah School of Medicine, Salt Lake City, Utah, 84132, United States; Dana S. Hardin 801-585-3485. Study chairs or principal investigators: Dana S. Hardin, Study Chair; University of Utah Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00014768 ·

Study of Uridine Triphosphate (UTP) as an Aerosol Spray for Cystic Fibrosis Condition(s): Cystic Fibrosis Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development; University of North Carolina Purpose - Excerpt: Objectives: I. Determine the stability of uridine triphosphate (UTP) and examine the metabolism of exogenous nucleotides on airway epithelial surfaces in patients with cystic fibrosis. II. Determine the acute safety and efficacy of aerosolized UTP in children with cystic fibrosis. Study Type: Interventional Contact(s): Michael R. Knowles 919-966-1077. Study chairs or principal investigators: Michael R. Knowles, Study Chair; University of North Carolina Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00004705

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Benefits and Risks17 What Are the Benefits of Participating in a Clinical Trial? If you are considering a clinical trial, it is important to realize that your child’s participation can bring many benefits: ·

A new treatment could be more effective than the current treatment for cystic fibrosis. 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.

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If the treatment is effective, then it may improve your child’s health.

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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.

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People who take part in trials contribute to scientific discoveries that may help others with cystic fibrosis. In cases where certain medical conditions run in families, your child’s participation may lead to better care or prevention for you and other family members. The Informed Consent

Once you agree to have your child 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 child, and your child’s 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 your child

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. 17

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

How Is Your Child’s Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect your child 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 your child’s safety. During a clinical trial, doctors will closely watch your child to see if the treatment is working and if he or she is 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. Your child will only be asked to participate in a clinical trial as a volunteer with your informed consent. What Are Your Child’s Rights in a Clinical Trial? If your child is eligible for a clinical trial, you will be given information to help you decide whether or not you want him or her to participate. You and your child have the right to: ·

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

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

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Know what is expected of your child.

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Know any costs involved for you or your child’s insurance provider.

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

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Talk openly with doctors and ask any questions.

After your child joins a clinical trial, you and your child have the right to: ·

Leave the study at any time. Participation is strictly voluntary.

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Receive any new information about the new treatment.

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Continue to ask questions and get answers.

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

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Know whether your child 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 child’s 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 your child to participation in the trial. If your child has health insurance, find out exactly what it will cover. If your child does not have health insurance, or if your child’s insurance policy will not cover care, talk to the clinic staff about other options for covering the costs. What Questions Should You Ask before Your Child Participates in a Clinical Trial? Questions you should ask when deciding whether or not to enroll your child in a clinical trial include the following: ·

What is the purpose of the clinical trial?

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What are the standard treatments for cystic fibrosis? Why do researchers think the new treatment may be better? What is likely to happen to my child with or without the new treatment?

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What tests and treatments will my child need? Will my child need surgery? Medication? Hospitalization?

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

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

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Will the treatment be uncomfortable? Will it make my child sick? If so, for how long?

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How will my child’s health be monitored?

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Where will my child need to go for the clinical trial?

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How much will it cost to participate in the study? What costs are covered by the study? How much will my child’s health insurance cover?

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Who will be in charge of my child’s care?

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Will taking part in the study affect my child’s daily life?

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How does my child feel about taking part in a clinical trial? Will other family members benefit from my child’s 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 the public and physicians with current information about clinical research across the broadest number of medical 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 “cystic fibrosis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

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

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

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For 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

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.

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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

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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

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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

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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

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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

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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

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

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH]

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Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bronchiectasis: Chronic dilatation of the bronchi marked by fetid breath and paroxysmal coughing, with the expectoration of mucopurulent matter. It may effect the tube uniformly (cylindric b.), or occur in irregular pockets (sacculated b.) or the dilated tubes may have terminal bulbous enlargements (fusiform b.). [EU] Bronchoscopy: A technique for visualizing the interior of bronchi and instilling or removing fluid or tissue samples by passing a lighted tube (bronchoscope) through the nose or mouth into the bronchi. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] DEXA: A method (dual energy X-ray absortiometry) used to estimate total body fat and percent of body fat. Potential disadvantages include whole body radiation and the long time required for scanning while the subject lies on a hard table. [NIH] Echocardiography: A test that bounces sound waves off the heart to produce pictures of its internal structures. [NIH] Electrocardiogram:

Measurement of electrical activity during heartbeats.

[NIH]

Electrolyte: A substance that dissociates into ions when fused or in solution,

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and thus becomes capable of conducting electricity; an ionic solute. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Gluconeogenesis: The process by which glucose is formed from a noncarbohydrate source. [NIH] 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] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Intravenous: Within a vein or veins. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Lavage: To wash the interior of a body organ. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] 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] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Mobility: Capability of movement, of being moved, or of flowing freely. [EU]

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Mycobacterium: An organism of the genus Mycobacterium. [EU] Neutrophil: Having an affinity for neutral dyes. [EU] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Pancrelipase: A preparation of hog pancreatic enzymes standardized for lipase content. [NIH] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Prevalence: The number of events, e.g., instances of a given disease or other condition, in a given population at a designated time. When used without qualification, the term usually refers to the situation at specific point in time (point prevalence). Prevalence is a number, not a rate. [NIH] Pruritus: 1. itching; an unpleasant cutaneous sensation that provokes the desire to rub or scratch the skin to obtain relief. 2. any of various conditions marked by itching, the specific site or type being indicated by a modifying term. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH]

Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [NIH] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]

Toxic: Pertaining to, due to, or of the nature of a poison or toxin; manifesting the symptoms of severe infection. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high

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molecular weight and antigenicity. [EU] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH]

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on cystic fibrosis. All too often, parents 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 cystic fibrosis. In Part II, as in Part I, our objective is not to interpret the latest advances on cystic fibrosis 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 cystic fibrosis is suggested.

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CHAPTER 4. STUDIES ON CYSTIC FIBROSIS Overview Every year, academic studies are published on cystic fibrosis 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 cystic fibrosis. 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 cystic fibrosis 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 cystic fibrosis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the

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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 “cystic fibrosis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Liver and Biliary Problems in Cystic Fibrosis Source: Seminars in Liver Disease. 18(3): 227-235. 1998. Contact: Available from Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001. (212) 760-0888. Fax (212) 947-1112. Website: www.thieme.com. Summary: Liver disease associated with cystic fibrosis (CF) has been increasingly diagnosed during recent years, probably due to the combined effect of systemic hepatic assessment and fewer deaths of CF patients from extra hepatic causes. This article reports on liver and biliary problems in CF. The authors note that in a group of 173 patients regularly followed at their center, cumulative incidence of liver disease was 17 percent over a mean period of 10 years. Although it generally runs a mild course, it is considered a major complication of CF which may limit survival and quality of life of affected patients. CF associated liver disease should be considered as the first inherited liver disorder in which the primary defect affects cholangiocyte transport systems. Although data assessing the effects of defective CF transmembrane regulator (CFTR) on cholangiocyte pathobiology are not yet available, the impaired secretory function of the biliary epithelium is considered responsible for reduced biliary fluidity and alkalinity and for subsequent bile duct damage by cytotoxic compounds or infectious agents. No clear association with specific CFTR mutations has been observed. Treatment with ursodeoxycholic acid, aimed at improving biliary secretion in terms of bile viscosity and bile acid composition, is the most useful therapeutic approach in CF associated liver disease. Beneficial effects on liver biochemistry, hepatic excretory function, liver histology, and essential fatty acid status have been reported, but there are no long term data on its effects on clinically relevant outcomes, such as death or need for transplantation. The effectiveness of bile acid therapy may be higher if started in patients with early stage liver disease, before symptoms have become clinically evident. The authors conclude that early diagnosis and identification of CF patients who are more liable to develop liver disease should be actively pursued. 2 figures. 1 table. 84 references. (AA-M).

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·

Pancreatic Insufficiency in Cystic Fibrosis and Pancreatic Exocrine Enzyme Replacement Source: Practical Gastroenterology. 20(1): 37-42. January 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. EMail: [email protected]. Summary: This article, one in a series on cystic fibrosis (CF), considers pancreatic insufficiency in CF and the use of pancreatic exocrine enzyme replacement. Pancreatic insufficiency in CF results in maldigestion of nutrients, which can, in turn, result in vitamin and trace element deficiencies, intussusception, distal intestinal obstruction, rectal prolapse, and growth retardation. In patients with CF and pancreatic insufficiency, the improvement in nutritional status following therapy with pancreatic enzymes reduced morbidity and mortality. The currently available pancreatic enzyme extracts decrease fecal nutrient losses, but they fail to fully correct maldigestion and malabsorption. In addition, there are several problems with the current preparations. The pancreatic extracts have fixed enzyme ratios, nonphysiologic route of administration, and variation in their content and manufacture. The normal pancreas secretes about 600,000 units of lipase a day, equivalent to 150 capsules a day of a low-dose, enteric-coated microsphere product (containing 4,000 units of lipase). On the other hand, high-dose enzyme is associated with strictures in the ascending colon. The pancreatic enzymes are delivered as rapidrelease enzyme preparations, at times with acid-reducing compounds, and as enteric-coated tablets or microspheres containing the enzymes. 1 table. 26 references. (AA-M).

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Gastrointestinal Function and Malabsorption in Cystic Fibrosis Source: Practical Gastroenterology. 20(3): 39-45. March 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. EMail: [email protected]. Summary: This article, one in a series on cystic fibrosis (CF), covers gastrointestinal (GI) function and malabsorption in CF. The authors note that, among Caucasians, CF is the most common mendelian lethal genetic disease of childhood. Since it is a systemic disease, affecting multiple organs, its clinical presentation varies widely. Pathology of the gastrointestinal tract, the pancreas, and the liver contributes significantly to the clinical variability of the disease. This review article summarizes current knowledge of the different gastrointestinal functions in CF: the gastric and duodenal secretory abnormalities, the slow intestinal transit,

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luminal mucus changes, protein, carbohydrate, and fat malabsorption, micronutrient availability, pancreatic dysfunction, bile acid abnormalities, and the newly described colonic stricture complication. 53 references. (AA). ·

Laboratory Evaluation of Pancreatic and Gut Function in Cystic Fibrosis Source: Practical Gastroenterology. 20(4): 39, 43-44, 46, 48, 51. April 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. EMail: [email protected]. Summary: This article, one in a series on cystic fibrosis (CF), addresses the laboratory evaluation of pancreatic and gut function in CF. The authors stress that the laboratory evaluation of the function of the various organs affected by CF is extremely important, as patient management should be tailored according to the severity of malfunction. In this article, the authors present an update focusing on the evaluation of pancreatic function. This includes noninvasive methods such as fecal fat analysis, which is the 'gold standard' study for demonstrating steatorrhea. The alternative fatty meal test is also described. Other studies of pancreatic function are discussed, of which the pancreozymin-secretin test is the most reliable but has the disadvantage of being invasive. Noninvasive alternatives are discussed. Specific tests covered are fecal fat analysis, immunoreactive assays for serum immunoreactive trypsinogen, the duallabeled Schilling test, the NBT-PABA test (bentiromide test), the pancreolauryl test, the fatty meal test, the Lundh test, the pancreozyminsecretin test, and a direct endoscopic secretin test. 1 table. 30 references. (AA-M).

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Hepatobiliary Complications of Cystic Fibrosis Source: Practical Gastroenterology. 20(6): 41-42, 44-46, 48-49. June 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. EMail: [email protected]. Summary: This article, one in a series on cystic fibrosis (CF), covers the hepatobiliary complications of CF. Liver disease in CF is caused by viscous, inspissated bile that interferes with bile flow and drainage and alters normal bile composition. The clinical spectrum includes fatty liver, cholestasis, cirrhosis, portal hypertension, and cholelithiasis. The consequences of liver involvement in CF are portal hypertension and its sequelae, such as variceal bleeding, deteriorating nutrition and growth,

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deteriorating respiratory status, and, to a much lesser degree, liver failure. Each patient must periodically undergo assessment of liver status (e.g., liver enzyme measurements and abdominal ultrasound). If there is evidence of liver impairment, a much more thorough evaluation should be performed, including scintigraphy or liver biopsy. If Doppler ultrasound demonstrates portal hypertension, an endoscopic assessment of varices is indicated. The therapeutic approach should initially be aimed toward prevention of the development of liver disease. This can be accomplished by controlling the nutritional status with pancreatic enzymes and vitamin supplements. Longterm administration of urodeoxycholic acid should be started at the first sign of liver involvement. In cases of decompensated cirrhosis, the patient should be referred for assessment for liver transplantation. The authors conclude that somatic gene therapy, at present in an experimental stage, may be the optimal solution to all liver-related problems in patients with CF. 2 tables. 23 references. (AA-M). ·

Patient with Cystic Fibrosis: A Case Study Source: Access. 15(8): 58-59,65. September-October 2001. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: This article summarizes a case report of a 33 year old Caucasian male who presented with the chief complaint of 'needing to have his teeth cleaned.' The patient had been last seen in a private dental office approximately 18 months previously; a history of annual prophylaxes since adulthood was reported. The medical history was significant for cystic fibrosis, for which the patient was taking 2.5 milligrams of Pulmozyme through a nebulizer once daily. He was also taking 4,000 units of Creon, a pancreatic enzyme, before meals and snacks, as well as fat-soluble vitamins (A, E, K) daily. The author describes the patient's oral health history, extraoral findings, intraoral findings, dental hygiene care planning, radiographic findings, implementation of the care plan, patient education and oral hygiene instructions, and prognosis. The author concludes with a brief description of cystic fibrosis and the implications of this disease for dental hygiene practice. 1 figure.

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Federally-Funded Research on Cystic Fibrosis The U.S. Government supports a variety of research studies relating to cystic fibrosis and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.18 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 CRISP Web 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 cystic fibrosis 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 cystic fibrosis 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 cystic fibrosis: ·

Project Title: A Linkage Study in Familial Pulmonary Fibrosis Principal Investigator & Institution: Schwartz, David A.; Professor of Medicine and Genetics; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2000; Project Start 0-AUG-2000; Project End 1-JUL2005 Summary: (Adapted from Investigator's Abstract) The overall goal of this project is to investigate inherited genetic factors that play a role in the development of pulmonary fibrosis. The overall hypothesis of this investigation is that inherited genetic factors predispose individuals to develop pulmonary fibrosis. The goal of this investigation is to identify a group of genetic loci that play a role in the development of familial pulmonary fibrosis. The overall hypothesis is supported by the following observations: familial pulmonary fibrosis is indistinguishable pathologically from idiopathic pulmonary fibrosis and appears to be inherited as an autosomal dominant trait with variable penetrance; pulmonary fibrosis is associated with pleiotropic genetic disorders, such

18 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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as Hermansky-Pudlak syndrome, neuofibromatosis, tuberous sclerosis, Neimann-Pick disease, Gaucher's disease, and familial hypocalciuric hypercalcemia; pulmonary fibrosis is frequently observed in autoimmune disease, including rheumatoid arthritis and systemic sclerosis; variable susceptibility is evident among workers who are reported to be exposed occupationally to similar concentrations of fibrogenic dusts; and inbred strains of mice differ in their susceptibility to fibrogenic dust. In conjunction with the exponential growth of human molecular genetics, the investigators state that these clinical observations suggest that a well organized approach to define the genetic determinants of pulmonary fibrosis is scientifically feasible and justified. This project proposes to use standard genetic methodology (linkage analysis) to investigate the distribution of polymorphisms for anonymous genetic markers in families with familial pulmonary fibrosis. The investigators state that their comprehensive genome-wide study, using standard genetic markers, will allow them to identify loci which subsequently may prove to contain novel genes that play a role in the pathogenesis of pulmonary fibrosis. Once genetic loci are defined in familial pulmonary fibrosis, candidate genes can be identified on the basis of both positional and functional criteria. Moreover, they note that this approach will provide basic information on high priority loci that will be applicable to the rapidly evolving dense human transcript map for pulmonary fibrosis in families with two or more cases of pulmonary fibrosis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Cystic Fibrosis Gene Modifier Study Principal Investigator & Institution: Marshall, Bruce C.; ; University of Utah 110 Park Bldg Salt Lake City, Ut 84112 Timing: Fiscal Year 2001 Summary: The specific aim of this multicenter study is to determine the location of a modifier gene. This will be accomplished by analyzing DNA from siblings with cystic fibrosis, their parents, and from individuals with cystic fibrosis who had meconium ileus at birth and their parents. A genetic modifier of cystic fibrosis in the mouse has been mapped to the proximal portion of mouse chromosome 17, a region syntenic with human chromosome 19q13. The cystic fibrosis modifier locus was mapped to the proximal region of mouse chromosome 7 through linkage studies with SFTR-deficient mice. Studies in humans have indicated that a cystic fibrosis modifier locus associated with meconium ileus, but not with pulmonary function abnormalities, does exist. To refine the mapping of the cystic fibrosis modifier locus, additional sibling pairs with cystic fibrosis were ascertained. A total of 161 cystic fibrosis families

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with at least two affected siblings (197 sibling pairs) have been collected from ten cystic fibrosis centers, including the University of Utah. This region will now be further refined by analyzing additional markers with testing for allelic associations with the disease locus. The Utah Cystic Fibrosis Center has contributed the majority of the ascertained subjects for this study. No results are yet available. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Fibroblast Specific Protein 1 in Pulmonary Fibrosis Principal Investigator & Institution: Blackwell, Timothy S.; Medicine; Vanderbilt University Nashville, Tn 37240 Timing: Fiscal Year 2001; Project Start 1-JUL-2001; Project End 0-JUN2005 Summary: Activated fibroblasts determine the extent of pulmonary fibrosis by their production of collagen and other matrix components. Fibroblast specific protein 1 (FSP1) is a member of the S100 protein superfamily and appears to play an early role in establishing the fibroblast phenotype. Although the origin of activated fibroblasts in pulmonary fibrosis is uncertain, recent studies in the kidney have shown that fibroblasts may arise from epithelium through a phenomenon called epithelial- mesenchymal transformation. Transforming growth factorbeta and other phenotypic modulators appear to regulate this process through up- regulation of FSP1 and other proteins that control fibroblast phenotype. In this project, we propose to investigate the following hypothesis. In lung fibrosis, activated lung fibroblasts are derived from airway epithelial cells as well as from resident interstitial fibroblasts. FSP1 is both a marker and important determinant of this cellular phenotype. The appearance and persistence of FSP1 expressing cells are crucial for determining the extent of lung fibrosis. We propose three specific aims: 1) to identify the role of FSP1+ cells in experimental lung fibrosis, 2) to determine whether epithelial-mesenchymal transformation occurs in the lungs and contributes to lung fibrosis in the mouse, 3) to modulate FSP1 expression and determine the effects on epithelialmesenchymal transformation and induction of lung fibrosis. Identification of a more useful fibroblast marker in the lungs would allow identification and monitoring of this cell population after fibrogenic stimuli and could foster targeted treatments that alter the accumulation or function of cells exhibiting the fibroblast phenotype. In addition, we plan to explore the origins of lung fibroblasts in experimental lung fibrosis with the hope that determining the presence and extent of epithelial-mesenchymal transformation in the lungs in these models will

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lead to innovative interventions to inhibit or reverse this transformation, thus limiting fibrosis and lung dysfunction. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Genetic and Anatomic Basis of the Fibrosis Syndromes Principal Investigator & Institution: Engle, Elizabeth C.; Assistant Professor; Children's Hospital (Boston) 300 Longwood Ave Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 0-AUG-2001; Project End 1-JUL2006 Summary: (provided by applicant): The congenital fibrosis syndromes are oculomotility disorders characterized by restrictive ophthalmoplegia with or without ptosis, and each disorder varies in the fixed position of the globes and in the specifically affected cranial nerve(s) and extraocular muscles (EOMs). The neuropathologic bases of two fibrosis syndromes have been described; Duane syndrome results from absence of the abducens nerve and nucleus, while CFEOM1 results from an absence of the superior division of the oculomotor nerve and corresponding oculomotor subnuclei. The laboratory's long-term goals are to uncover the molecular basis of the fibrosis syndromes and to study the development of the oculomotor lower motor neuron system. Toward these goals, we have genetically defined four congenital fibrosis loci and one congenital ptosis locus, and are in the process of positionally cloning these genes. In this grant, we seek funding to address the following specific aims: (1) Identify families with the congenital fibrosis syndromes for our clinical and genetic studies and analyze their DNA for linkage to the known CFEOM loci. (2) Define the anatomic and functional basis of CFEOM by high-resolution orbital MRI studies in affected members of genetically defined families. (3) Clone the CFEOM1 disease gene (which is mutated in the most common inherited form of the congenital fibrosis syndromes) and analyze CFEOM1 families for disease-causing mutations. (4) Initiate structural and functional characterization of the CFEOM1 RNA and protein product. Significance: The molecular bases of strabismic disorders remain poorly understood. Though rare, several of the fibrosis syndromes are inherited, and thus provide a unique opportunity to investigate the etiology of this subset of strabismic disorders. Our large collection of CFEOM1 families, coupled with a detailed physical map and access to genomic sequence within the CFEOM1 critical region, places us in a unique position to identify this disease gene. In addition, the correlation of this genetic data with the proposed clinical, anatomic, and functional characterization of genetically defined patients provides a unique and strong foundation for phenotype-

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genotype correlations and functional studies. By defining the genetic and anatomic bases of CFEOM1, we will develop a tool with which to study its molecular basis and to search for related fibrosis genes, and with which we should gain important new insights into brainstem cranial nerve development. These data will be invaluable to our understanding of the developmental roles of these genes, and should also contribute to improved therapy of the fibrosis syndromes. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: IB367 in Adult Patients with Cystic Fibrosis Principal Investigator & Institution: Konstan, Michael W.; ; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2000; Project Start 1-DEC-1978; Project End 0-NOV2003 Summary: This is a Phase I, randomized, placebo-controlled, doubleblind, multicenter, safety and tolerability study of ascending inhaled doses of IB-367 in adult patients with cystic fibrosis. Patients will be enrolled in groups of eight. In each group, patients will be randomized in a 3:1 fashion (6 active; 2 placebo) to receive IB-367 or placebo. All patients will be monitored as in-patients during the study. Each patient will participate in one treatment period only. This study will be conducted in two parts (A & B). During Part A, a group of 8 patients will be monitored in a single-blind, dose escalation phase for observation of any adverse events. Doses in this part of the study will vary by increasing administration of a single concentration of study drug. If IB-367 is well tolerated during the single-blind dose escalation, then subsequent cohorts of patients will receive single ascending doses administered in a doubleblind manner (Part B). Patients in both parts of the study will be pretreated with an inhaled bronchodilator prior to administering each dose. Persistent airway infections remain a major clinical problem for patients with cystic fibrosis. These infections are particularly difficult to treat because conventional antibiotics often do not achieve adequate delivery of drug to the site of infection and because the risk of inducing bacterial resistance often limits long-term therapies. IntraBiotics is developing a series of antimicrobial peptides based on protegrins, a family of naturally derived host-defense peptides initially isolated from procine neutrophils. One such protegrin analog, IB-367, has been formulated as a solution for inhalation to be used in the treatment of respiratory infections, such as those in patients with cystic fibrosis. As a class, peptides of this group are broad spectrum, microbicidal agents that kill microorganisms rapidly by disrupting membrane integrity. Recent research has shown that high salt concentrations in the airways of patients with cystic fibrosis causes local

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inhibition of an endogenous antimicrobial substance, and that this inhibition may be one of the factors predisposing patients with cystic fibrosis to pulmonary infections. The bactericidal activity of IB-367 is not significantly affected by sodium chloride concentrations up to 182 mM, the level reported in cystic fibrosis airway surface fluid. We hypothesize that inhaled IB-367 could replace the inactivated, naturally occurring antimicrobial host defense molecules in patients with cystic fibrosis and provide a substantial improvement in patient outcome. The primary objectives are: 1) to determine the safety and tolerability of ascending doses of inhaled IB-367 in adult patients with cystic fibrosis 2) To determine whether potential bronchial reactivity to IB-367 is prevented by the prophylactic use of an inhaled bronchodilator in adult patients with cystic fibrosis as measured by change in FEV1 pre-and post-dose. The secondary objectives are: 1) to monitor for evidence of systemic absorption of IB-367 characterized by vasodilatory response or other toxicities. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central19 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).20 Access to this growing archive of e-journals is free and unrestricted.21 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “cystic fibrosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for cystic fibrosis in the PubMed Central database: ·

In vivo activation of the cystic fibrosis transmembrane conductance regulator mutant [Delta]F508 in murine nasal epithelium by Thomas J. Kelley, Kirk Thomas, Laura J. H. Milgram, and Mitchell L. Drumm; 1997 March 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20135

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 20 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. 21 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. 19

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A conditional probability analysis of cystic fibrosis transmembrane conductance regulator gating indicates that ATP has multiple effects during the gating cycle by Daniel J. Hennager, Mutsuhiro Ikuma, Toshinori Hoshi, and Michael J. Welsh; 2001 March 13 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=30698

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A C-terminal motif found in the [beta]2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na + /H + exchanger regulatory factor family of PDZ proteins by Randy A. Hall, Lynda S. Ostedgaard, Richard T. Premont, Jeremy T. Blitzer, Nadeem Rahman, Michael J. Welsh, and Robert J. Lefkowitz; 1998 July 21 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21104

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A Cystic Fibrosis Pancreatic Adenocarcinoma Cell Line by RA Schoumacher, J Ram, MC Iannuzzi, NA Bradbury, RW Wallace, CT Hon, DR Kelly, SM Schmid, FB Gelder, TA Rado, and RA Frizzell; 1990 May 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=54034

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A functional R domain from cystic fibrosis transmembrane conductance regulator is predominantly unstructured in solution by Lynda S. Ostedgaard, Olafur Baldursson, Daniel W. Vermeer, Michael J. Welsh, and Andrew D. Robertson; 2000 May 9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=25884

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A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr [minus sign] /[minus sign] mice by Steven D. Freedman, Mark H. Katz, Eliza M. Parker, Michael Laposata, Mark Y. Urman, and Juan G. Alvarez; 1999 November 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24179

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A1 Adenosine-Receptor Antagonists Activate Chloride Efflux from Cystic Fibrosis Cells by O Eidelman, C Guay-Broder, PJM van Galen, KA Jacobson, C Fox, RJ Turner, ZI Cabantchik, and HB Pollard; 1992 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49332

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Abnormal Secretagogue-Induced Intracellular Free Ca2+ Regulation in Cystic Fibrosis Nasal Epithelial Cells by L Reinlib, DJ Jefferson, FC Marini, and M Donowitz; 1992 April 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48782

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An Approach for Treating the Hepatobiliary Disease of Cystic Fibrosis by Somatic Gene Transfer by Y Yang, SE Raper, JA Cohn, JF Engelhardt, and JM Wilson; 1993 May 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=46560

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Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells by Erik M. Schwiebert, Luis P. Cid-Soto, Diane Stafford, Mark Carter, Carol J. Blaisdell, Pamela L. Zeitlin, William B. Guggino, and Garry R. Cutting; 1998 March 31 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19931

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Antisense Oligodeoxynucleotide to the Cystic Fibrosis Gene Inhibits Anion Transport in Normal Cultured Sweat Duct Cells by EJ Sorscher, KL Kirk, ML Weaver, T Jilling, JE Blalock, and RD LeBoeuf; 1991 September 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52382

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Antisense Oligodeoxynucleotides to the Cystic Fibrosis Transmembrane Conductance Regulator Inhibit cAMP-Activated but not Calcium-Activated Chloride Currents by JA Wagner, TV McDonald, PT Nghiem, AW Lowe, H Schulman, DC Gruenert, L Stryer, and P Gardner; 1992 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49588

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Association of variant alleles of mannose binding lectin with severity of pulmonary disease in cystic fibrosis: cohort study by M Gabolde, M Guilloud-Bataille, J Feingold, and C Besmond; 1999 October 30 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28266

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Basal Expression of the Cystic Fibrosis Transmembrane Conductance Regulator Gene is Dependent on Protein Kinase A Activity by RA McDonald, RP Matthews, RL Idzerda, and GS McKnight; 1995 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=41379

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Bicarbonate Conductance and pH Regulatory Capability of Cystic Fibrosis Transmembrane Conductance Regulator by JH Poulsen, H Fischer, B Illek, and TE Machen; 1994 June 7 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43990

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Bronchial artery delivery of viral vectors for gene delivery in cystic fibrosis; superior to airway delivery? by Ameet Bakhai, Desmond J. Sheridan, and Charles C. Coutelle; 2002 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=107842

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Burkholderia cepacia Complex Infection in Italian Patients with Cystic Fibrosis: Prevalence, Epidemiology, and Genomovar Status by Antonella Agodi, Eshwar Mahenthiralingam, Martina Barchitta, Viviana Giannino, Agata Sciacca, and Stefania Stefani; 2001 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88256&ren dertype=external

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Calcium and cAMP Activate Different Chloride Channels in the Apical Membrane of Normal and Cystic Fibrosis Epithelia by MP Anderson and MJ Welsh; 1991 July 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52010

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cAMP-Inducible Chloride Conductance in Mouse Fibroblast Lines Stably Expressing the Human Cystic Fibrosis Transmembrane Conductance Regulator by JM Rommens, S Dho, CE Bear, N Kartner, D Kennedy, JR Riordan, L Tsui, and JK Foskett; 1991 September 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52328

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'CFTR-opathies': disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations by Peadar G. Noone and Michael R. Knowles; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=64805

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Characterization of Immortal Cystic Fibrosis Tracheobronchial Gland Epithelial Cells by AL Cozens, MJ Yezzi, L Chin, EM Simon, WE Finkbeiner, JA Wagner, and DC Gruenert; 1992 June 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49251

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Characterization of the Cystic Fibrosis Transmembrane Conductance Regulator in a Colonocyte Cell Line by JA Cohn, AC Nairn, CR Marino, O Melhus, and J Kole; 1992 March 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48653

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Chloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator by Erik M. Schwiebert, Marcelo M. Morales, Sreenivas Devidas, Marie E. Egan, and William B. Guggino; 1998 March 3 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19458

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Chronic Melioidosis in a Patient with Cystic Fibrosis by Tanja Schulin and Ivo Steinmetz; 2001 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88000&ren dertype=external

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Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study by Ravi Mahadeva, Kevin Webb, Roger C Westerbeek, Nick R Carroll, Mary E Dodd, Diana Bilton, and David A Lomas; 1998 June 13 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28574

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Cloning and Expression of a Human P2U Nucleotide Receptor, a Target for Cystic Fibrosis Pharmacotherapy by CE Parr, DM Sullivan, AM Paradiso, ER Lazarowski, LH Burch, JC Olsen, L Erb, GA Weisman, RC Boucher, and JT Turner; 1994 April 12 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43559

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Colloquium:Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections by Gerald B. Pier; 2000 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=34018

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Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes by Rachel E. Ellsworth, D. Curtis Jamison, Jeffrey W. Touchman, Stephanie L. Chissoe, Valerie V. Braden Maduro, Gerard G. Bouffard, Nicole L. Dietrich, Stephen M. Beckstrom-Sternberg, Leslie M. Iyer, Lauren A. Weintraub, Marc Cotton, Laura Courtney, Jennifer Edwards, Rachel Maupin, Philip Ozersky, Theresa Rohlfing, Patricia Wohldmann, Tracie Miner, Kimberley Kemp, Jason Kramer, Ian Korf, Kimberlie Pepin, Lucinda Antonacci-Fulton, Robert S. Fulton, Patrick Minx, LaDeana W. Hillier, Richard K. Wilson, Robert H. Waterston, Webb Miller, and Eric D. Green; 2000 February 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=15558

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Comparison of Agar Diffusion Methodologies for Antimicrobial Susceptibility Testing of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients by Jane L. Burns, Lisa Saiman, Susan Whittier, Davise Larone, Jay Krzewinski, Zhenling Liu, Steven A. Marshall, and Ronald N. Jones; 2000 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86597&ren dertype=external

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Comparison of Isolation Media for Recovery of Burkholderia cepacia Complex from Respiratory Secretions of Patients with Cystic Fibrosis by Deborah Henry, Maureen Campbell, Colleen McGimpsey, Alison

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Clarke, Laurie Louden, Jane L. Burns, Martha H. Roe, Peter Vandamme, and David Speert; 1999 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88640&ren dertype=external ·

Correction: Cloning and Expression of a Human P2U Nucleotide Receptor, a Target for Cystic Fibrosis Pharmacotherapy by F Becq, TJ Jensen, X Chang, A Savoia, JM Rommens, L Tsui, M Buchwald, JR Riordan, and HW Hanrahan; 1994 September 13 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=44767

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Cystic Fibrosis Epithelial Cells have a Receptor for Pathogenic Bacteria on their Apical Surface by L Imundo, J Barasch, A Prince, and Q AlAwqati; 1995 March 28 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=42350

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Cystic Fibrosis Gene Encodes a cAMP-Dependent Chloride Channel in Heart by P Hart, JD Warth, PC Levesque, ML Collier, Y Geary, B Horowitz, and JR Hume; 1996 June 25 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=39024

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Cystic Fibrosis Gene Expression is not Correlated with Rectifying ClChannels by CL Ward, ME Krouse, DC Gruenert, RR Kopito, and JJ Wine; 1991 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51855

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Cystic Fibrosis Transmembrane Conductance Regulator Activation Stimulates Endosome Fusion in vivo by J Biwersi, N Emans, and AS Verkman; 1996 October 29 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=38018

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Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung by Gerald B. Pier, Martha Grout, and Tanweer S. Zaidi; 1997 October 28 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23711

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Defective regulatory volume decrease in human cystic fibrosis tracheal cells because of altered regulation of intermediate conductance Ca2 +dependent potassium channels by Esther Vazquez, Muriel Nobles, and Miguel A. Valverde; 2001 April 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=33209

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Development of rRNA-Based PCR Assays for Identification of Burkholderia cepacia Complex Isolates Recovered from Cystic Fibrosis Patients by John J. LiPuma, Betty Jo Dulaney, Jennifer D. McMenamin, Paul W. Whitby, Terrence L. Stull, Tom Coenye, and Peter Vandamme; 1999 October http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85518&ren dertype=external

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Differentiation of Burkholderia Species by PCR-Restriction Fragment Length Polymorphism Analysis of the 16S rRNA Gene and Application to Cystic Fibrosis Isolates by Christine Segonds, Thierry Heulin, Nicole Marty, and Gerard Chabanon; 1999 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85118&ren dertype=external

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Distribution of Genes Encoding Putative Transmissibility Factors among Epidemic and Nonepidemic Strains of Burkholderia cepacia from Cystic Fibrosis Patients in the United Kingdom by Fiona E. Clode, Mary E. Kaufmann, Henry Malnick, and Tyrone L. Pitt; 2000 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86581&ren dertype=external

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Engineering Actin-Resistant Human DNase I for Treatment of Cystic Fibrosis by JS Ulmer, A Herzka, KJ Toy, DL Baker, AH Dodge, D Sinicropi, S Shak, and RA Lazarus; 1996 August 6 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=38651

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Evaluation of Reference Dilution Test Methods for Antimicrobial Susceptibility Testing of Pseudomonas aeruginosa Strains Isolated from Patients with Cystic Fibrosis by Lisa Saiman, Jane L. Burns, Susan Whittier, Jay Krzewinski, Steve A. Marshall, and Ronald N. Jones; 1999 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85429&ren dertype=external

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Expression of the Cystic Fibrosis Transmembrane Conductance Regulator Gene in the Respiratory Tract of Normal Individuals and Individuals with Cystic Fibrosis by BC Trapnell, C Chu, PK Paakko, TC Banks, K Yoshimura, VJ Ferrans, MS Chernick, and RG Crystal; 1991 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52127

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Fatal Pulmonary Infection Due to Multidrug-Resistant Mycobacterium abscessus in a Patient with Cystic Fibrosis by Maurizio Sanguinetti,

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Fausta Ardito, Ersilia Fiscarelli, Marilena La Sorda, Patrizia D'Argenio, Gabriella Ricciotti, and Giovanni Fadda; 2001 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87830&ren dertype=external ·

From the Cover:Compartmentalized autocrine signaling to cystic fibrosis transmembrane conductance regulator at the apical membrane of airway epithelial cells by Pingbo Huang, Eduardo R. Lazarowski, Robert Tarran, Sharon L. Milgram, Richard C. Boucher, and M. Jackson Stutts; 2001 November 20 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=61178

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Functional Roles of the Nucleotide-Binding Folds in the Activation of the Cystic Fibrosis Transmembrane Conductance Regulator by LS Smit, DJ Wilkinson, MK Mansoura, FS Collins, and DC Dawson; 1993 November 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47693

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Glycosylation and the cystic fibrosis transmembrane conductance regulator by Thomas F. Scanlin and Mary Catherine. Glick; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59516

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GTP-Binding Proteins Inhibit cAMP Activation of Chloride Channels in Cystic Fibrosis Airway Epithelial Cells by EM Schwiebert, N Kizer, DC Gruenert, and BA Stanton; 1992 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50393

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Heterogeneity of Pseudomonas aeruginosa in Brazilian Cystic Fibrosis Patients by Suzane Silbert, Afonso Luis Barth, and Helio S. Sader; 2001 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88474&ren dertype=external

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Hsp70 Molecular Chaperone Facilitates Endoplasmic Reticulumassociated Protein Degradation of Cystic Fibrosis Transmembrane Conductance Regulator in Yeast by Yimao Zhang, Gaby Nijbroek, Mara L. Sullivan, Ardythe A. McCracken, Simon C. Watkins, Susan Michaelis, and Jeffrey L. Brodsky; 2001 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=34585

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Identification and Antimicrobial Susceptibility of Alcaligenes xylosoxidans Isolated from Patients with Cystic Fibrosis by Lisa Saiman, Yunhua Chen, Setareh Tabibi, Pablo San Gabriel, Juyan Zhou, Zhenling Liu, Lena Lai, and Susan Whittier; 2001 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88468&ren dertype=external

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Identification of a Protein that Confers Calcitonin Gene-Related Peptide Responsiveness to Oocytes by Using a Cystic Fibrosis Transmembrane Conductance Regulator Assay by AE Luebke, GP Dahl, BA Roos, and IM Dickerson; 1996 April 16 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=39630

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Identification of an Ion Channel-Forming Motif in the Primary Structure of CFTR, the Cystic Fibrosis Chloride Channel by M OblattMontal, GL Reddy, T Iwamoto, JM Tomich, and M Montal; 1994 February 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43186

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Identification of Mutations in Regions Corresponding to the Two Putative Nucleotide (ATP)-Binding Folds of the Cystic Fibrosis Gene by B Kerem, J Zielenski, D Markiewicz, D Bozon, E Gazit, J Yahav, D Kennedy, JR Riordan, FS Collins, JM Rommens, and L Tsui; 1990 November 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=54973

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Immunocytochemical Localization of the Cystic Fibrosis Gene Product CFTR by I Crawford, PC Maloney, PL Zeitlin, WB Guggino, SC Hyde, H Turley, KC Gatter, A Harris, and CF Higgins; 1991 October 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52694

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Impact of Microbiology Practice on Cumulative Prevalence of Respiratory Tract Bacteria in Patients with Cystic Fibrosis by Michael R. Shreve, Steven Butler, Haley J. Kaplowitz, Harvey R. Rabin, Dennis Stokes, Michael Light, Warren E. Regelmann, and Investigators for the Epidemiologic Study of Cystic Fibrosis; 1999 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84543&ren dertype=external

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Impaired Cell Volume Regulation in Intestinal Crypt Epithelia of Cystic Fibrosis Mice by MA Valverde, JA O'Brien, FV Sepulveda, RA Ratcliff, MJ Evans, and WH Colledge; 1995 September 26 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=40919

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Intrinsic Anion Channel Activity of the Recombinant First Nucleotide Binding Fold Domain of the Cystic Fibrosis Transmembrane Regulator Protein by N Arispe, E Rojas, J Hartman, EJ Sorscher, and HB Pollard; 1992 March 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48487

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Ketoconazole Activates Cl- Conductance and Blocks Cl- and Fluid Absorption by Cultured Cystic Fibrosis (CFPAC-1) Cells by U Kersting, D Kersting, and KR Spring; 1993 May 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=46443

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Mechanism of Conversion to Mucoidy in Pseudomonas aeruginosa Infecting Cystic Fibrosis Patients by DW Martin, MJ Schurr, MH Mudd, JRW Govan, BW Holloway, and V Deretic; 1993 September 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47359

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Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl[minus sign] channel activation by Arie. B. Vaandrager, Albert Smolenski, Ben C. Tilly, Adriaan B. Houtsmuller, Ehrich M. E. Ehlert, Alice G. M. Bot, Marcel Edixhoven, Wendy E. M. Boomaars, Suzanne M. Lohmann, and Hugo R. de Jonge; 1998 February 17 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19047

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Molecular Analysis of the Ovine Cystic Fibrosis Transmembrane Conductanvce Regulator Gene by SJ Tebbutt, CJC Wardle, DF Hill, and A Harris; 1995 March 14 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=42470

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Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung by J. F. Poschet, J. C. Boucher, L. Tatterson, J. Skidmore, R. W. Van Dyke, and V. Deretic; 2001 November 20 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=61151

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Mutant Cystic Fibrosis Transmembrane Conductance Regulator Inhibits Acidification and Apoptosis in C127 Cells: Possible Relevance to Cystic Fibrosis by RA Gottlieb and A Dosanjh; 1996 April 16 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=39654

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Mutation Detection by Mismatch Binding Protein, MutS, in Amplified DNA: Application to the Cystic Fibrosis Gene by A Lishanski, EA Ostrander, and J Rine; 1994 March 29 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43432

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Note:Capillary Electrophoresis --Single-Strand Conformation Polymorphism Analysis for Rapid Identification of Pseudomonas aeruginosa and Other Gram-Negative Nonfermenting Bacilli Recovered from Patients with Cystic Fibrosis by Rafiaa Ghozzi, Philippe Morand, Agnes Ferroni, Jean-Luc Beretti, Edouard Bingen, Christine Segonds, Marie-Odile Husson, Daniel Izard, Patrick Berche, and JeanLouis Gaillard; 1999 October http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85573&ren dertype=external

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Note:Epidemiological Analysis of Sequential Pseudomonas aeruginosa Isolates from Chronic Bronchiectasis Patients without Cystic Fibrosis by I. Pujana, L. Gallego, G. Martin, F. Lopez, J. Canduela, and R. Cisterna; 1999 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85036&ren dertype=external

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Note:Molecular Typing and Exopolysaccharide Biosynthesis of Burkholderia cepacia Isolates from a Portuguese Cystic Fibrosis Center by Joao A. Richau, Jorge H. Leitao, Manuela Correia, Luis Lito, Maria Jose Salgado, Celeste Barreto, Paola Cescutti, and Isabel Sa-Correia; 2000 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86514&ren dertype=external

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Note:Pneumocystis carinii Carriage among Cystic Fibrosis Patients, as Detected by Nested PCR by Andreas Sing, Anna Maria Geiger, Michael Hogardt, and Jurgen Heesemann; 2001 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88220&ren dertype=external

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Note:Recovery of Mycobacteria from Patients with Cystic Fibrosis by Franz-Christoph Bange, Philip Kirschner, and Eric C. Bottger; 1999 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85755&ren dertype=external

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Note:Utility of Commercial Systems for Identification of Burkholderia cepacia Complex from Cystic Fibrosis Sputum Culture by Deborah Blecker Shelly, Theodore Spilker, Edward J. Gracely, Tom Coenye, Peter Vandamme, and John J. LiPuma; 2000 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87204&ren dertype=external

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Novel Bacterium Isolated from a Lung Transplant Patient with Cystic Fibrosis by Christian Pitulle, Diane M. Citron, Barry Bochner, Richard Barbers, and Maria D. Appleman; 1999 December http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85827&ren dertype=external

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PCR-Based Detection and Identification of Burkholderia cepacia Complex Pathogens in Sputum from Cystic Fibrosis Patients by Andrew McDowell, Eshwar Mahenthiralingam, John E. Moore, Kerstin E. A. Dunbar, A. Kevin Webb, Mary E. Dodd, S. Lorraine Martin, B. Cherie Millar, Christopher J. Scott, Mary Crowe, and J. Stuart Elborn; 2001 December http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88532&ren dertype=external

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Protein phosphatase 2C dephosphorylates and inactivates cystic fibrosis transmembrane conductance regulator by Sue M. Travis, Herbert A. Berger, and Michael J. Welsh; 1997 September 30 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23594

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Questionnaire survey of urinary incontinence in women with cystic fibrosis by A Orr, R J McVean, A K Webb, and M E Dodd; 2001 June 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=33391

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Rapid Endocytosis of the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel by LS Prince, RB Workman, Jr, and RB Marchase; 1994 May 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43958

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Recombinant Human DNase I Reduces the Viscosity of Cystic Fibrosis Sputum by S Shak, DJ Capon, R Hellmiss, SA Marsters, and CL Baker; 1990 December 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=55129

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Red-Pigmented Candida albicans in Patients with Cystic Fibrosis by Marie-Louise Kerkmann, Markus Schuppler, Klaus-Dieter Paul, Gabriele Schoenian, and Maudy T. Smith; 1999 January http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84240&ren dertype=external

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Regulation of Cl- Channels in Normal and Cystic Fibrosis Airway Epithelial Cells by Extracellular ATP by MJ Stutts, TC Chinet, SJ Mason, JM Fullton, LL Clarke, and RC Boucher; 1992 March 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48504

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Regulation of cystic fibrosis transmembrane conductance regulator single-channel gating by bivalent PDZ-domain-mediated interaction by Viswanathan Raghuram, Don-On Daniel Mak, and J. Kevin Foskett; 2001 January 30 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14749

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Regulation of the Gating of Cystic Fibrosis Transmembrane Conductance Regulator C1 Channels by Phosphorylation and ATP Hydrolysis by T Hwang, G Nagel, AC Nairn, and DC Gadsby; 1994 May 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43855

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Relationship of a Non-Cystic Fibrosis Transmembrane Conductance Regulator- Mediated Chloride Conductance to Organ-Level Disease in Cftr(-/-) Mice by LL Clarke, BR Grubb, JR Yankaskas, CU Cotton, A McKenzie, and RC Boucher; 1994 January 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=42972

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Sensitivity of a Renal K+ Channel (ROMK2) to the Inhibitory Sulfonylurea Compound Glibenclamide is Enhanced by Coexpression with the ATP-Binding Cassette Transporter Cystic Fibrosis Transmembrane Regulator by CM McNicholas, WB Guggino, EM Schwiebert, SC Hebert, G Giebisch, and ME Egan; 1996 July 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=38879

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Single Nucleotide Primer Extension to Detect Genetic Diseases: Experimental Application to Hemophilia B (Factor IX) and Cystic Fibrosis Genes by MN Kuppuswamy, JW Hoffman, CK Kasper, SG Spitzer, SL Groce, and SP Bajaj; 1991 February 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50973

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Specific and Rapid Detection by Fluorescent In Situ Hybridization of Bacteria in Clinical Samples Obtained from Cystic Fibrosis Patients by Michael Hogardt, Karlheinz Trebesius, Anna M. Geiger, Mathias Hornef, Josef Rosenecker, and Jurgen Heesemann; 2000 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86213&ren dertype=external

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Stable in vivo Expression of the Cystic Fibrosis Transmembrane Conductance Regulator with an Adeno-Associated Virus Vector by TR Flotte, SA Afione, C Conrad, SA McGarth, R Solow, H Oka, PL Zeitlin, WB Guggino, and BJ Carter; 1993 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47827

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Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na +] and pH but elevated viscosity by Sujatha Jayaraman, Nam Soo Joo, Bruce Reitz, Jeffrey J. Wine, and A. S. Verkman; 2001 July 3 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=35477

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Taking stock of gene therapy for cystic fibrosis by Myra Stern, Duncan M Geddes, and Eric WFW Alton; 2000 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59546

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The Common Variant of Cystic Fibrosis Transmembrane Conductance Regulator is Recognized by hsp70 and Degraded in a Pre-Golgi Nonlysosomal Compartment by Y Yang, S Janich, JA Cohn, and JM Wilson; 1993 October 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47592

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The Gene for Congenital Chloride Diarrhea Maps Close to but is Distinct from the Gene for Cystic Fibrosis Transmembrane Conductance Regulator by J Kere, P Sistonen, C Holmberg, and ADL Chapelle; 1993 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47842

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Toward an Animal Model of Cystic Fibrosis: Targeted Interruption of Exon 10 of the Cystic Fibrosis Transmembrane Regulator Gene in Embryonic Stem Cells by BH Koller, H Kim, AM Latour, K Brigman, RC Boucher, Jr, P Scambler, B Wainwright, and O Smithies; 1991 December 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53004

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Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease by Jian-Dong Li, Austin F. Dohrman, Marianne Gallup, Susumu Miyata,

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James R. Gum, Young S. Kim, Jay A. Nadel, Alice Prince, and Carol B. Basbaum; 1997 February 4 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19623 ·

Two Cystic Fibrosis Transmembrane Conductance Regulator Mutations Have Different Effects on Both Pulmonary Phenotype and Regulation of Outwardly Rectified Chloride Currents by SB Fulmer, EM Schwiebert, MM Morales, WB Guggino, and GR Cutting; 1995 July 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=41423

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Unique presentations and chronic complications in adult cystic fibrosis: do they teach us anything about CFTR? by Michael P. Boyle; 2000 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59552

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Uptake of Fluorescent Dyes Associated with the Functional Expression of the Cystic Fibrosis Transmembrane Conductance Regulator in Epithelial Cells by RP Wersto, ER Rosenthal, RG Crystal, and KR Spring; 1996 February 6 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=40050

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Use of Random Amplified Polymorphic DNA PCR To Examine Epidemiology of Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans from Patients with Cystic Fibrosis by Jay W. Krzewinski, Chau D. Nguyen, Jessica M. Foster, and Jane L. Burns; 2001 October http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88395&ren dertype=external

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.22 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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

Self-administered chest physiotherapy in cystic fibrosis: a comparative study of high-pressure PEP and autogenic drainage. Author(s): Pfleger A, Theissl B, Oberwaldner B, Zach MS. Source: Lung. 1992; 170(6): 323-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1434782&dopt=Abstract

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Self-hypnosis for patients with cystic fibrosis. Author(s): Anbar RD. Source: Pediatric Pulmonology. 2000 December; 30(6): 461-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11109057&dopt=Abstract

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Single- and multiple-dose-response relationships of beta-carotene in cystic fibrosis. Author(s): Homnick DN, Spillers CR, Cox SR, Cox JH, Yelton LA, DeLoof MJ, Oliver LK, Ringer TV. Source: The Journal of Pediatrics. 1995 September; 127(3): 491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7658286&dopt=Abstract

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Sputum rheology changes in cystic fibrosis lung disease following two different types of physiotherapy: flutter vs autogenic drainage. Author(s): App EM, Kieselmann R, Reinhardt D, Lindemann H, Dasgupta B, King M, Brand P. Source: Chest. 1998 July; 114(1): 171-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9674466&dopt=Abstract

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Studies on cystic fibrosis using isoelectric focusing. IV. Distinction between ciliary dyskinesia activity in cystic fibrosis and asthmatic sera and association of cystic fibrosis protein with the activity in cystic

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fibrosis serum. Author(s): Wilson GB, Fudenberg HH. Source: Pediatric Research. 1977 April; 11(4): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=846785&dopt=Abstract ·

Successful treatment of acute lymphoblastic leukemia in a child with cystic fibrosis. Author(s): Gururangan S, Horner M, Rodman JH, Marina NM. Source: Medical and Pediatric Oncology. 1994; 22(6): 414-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8152404&dopt=Abstract

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Supplementation with carotenoids corrects increased lipid peroxidation in children with cystic fibrosis. Author(s): Lepage G, Champagne J, Ronco N, Lamarre A, Osberg I, Sokol RJ, Roy CC. Source: The American Journal of Clinical Nutrition. 1996 July; 64(1): 8793. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8669420&dopt=Abstract

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Systematic reviews in cystic fibrosis. Author(s): Smyth RL, Cheng K, Motley J. Source: Journal of the Royal Society of Medicine. 1998; 91 Suppl 34: 19-24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9709384&dopt=Abstract

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Taurine supplementation, fat absorption, and growth in cystic fibrosis. Author(s): Thompson GN, Robb TA, Davidson GP. Source: The Journal of Pediatrics. 1987 October; 111(4): 501-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3309233&dopt=Abstract

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The absorption and effect of dietary supplementation with omega-3 fatty acids on serum leukotriene B4 in patients with cystic fibrosis. Author(s): Kurlandsky LE, Bennink MR, Webb PM, Ulrich PJ, Baer LJ. Source: Pediatric Pulmonology. 1994 October; 18(4): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7838619&dopt=Abstract

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The current physical therapy regimens of 108 consecutive patients attending a regional cystic fibrosis unit. Author(s): Morton S, Gilbert J, Littlewood JM. Source: Scand J Gastroenterol Suppl. 1988; 143: 110-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3164494&dopt=Abstract

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The effect of oral zinc supplementation on plasma levels of vitamin A and retinol-binding protein in cystic fibrosis. Author(s): Palin D, Underwood BA, Denning CR. Source: The American Journal of Clinical Nutrition. 1979 June; 32(6): 1253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=571673&dopt=Abstract

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The effect of parental relationships on the management of cystic fibrosis and guidelines for social work intervention. Author(s): Oppenheimer JR, Rucker RW. Source: Soc Work Health Care. 1980 Summer; 5(4): 409-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7434143&dopt=Abstract

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The effects of biofeedback assisted breathing retraining on lung functions in patients with cystic fibrosis. Author(s): Delk KK, Gevirtz R, Hicks DA, Carden F, Rucker R. Source: Chest. 1994 January; 105(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8275737&dopt=Abstract

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The effects of inspiratory muscle training in patients with cystic fibrosis. Author(s): Asher MI, Pardy RL, Coates AL, Thomas E, Macklem PT. Source: Am Rev Respir Dis. 1982 November; 126(5): 855-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7149451&dopt=Abstract

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The effects of self-hypnosis for children with cystic fibrosis: a pilot study. Author(s): Belsky J, Khanna P.

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Source: Am J Clin Hypn. 1994 April; 36(4): 282-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8203356&dopt=Abstract ·

The influence of long-term cimetidine as an adjuvant to pancreatic enzyme therapy in cystic fibrosis. Author(s): Chalmers DM, Brown RC, Miller MG, Clarke PC, Kelleher J, Littlewood JM, Losowsky MS. Source: Acta Paediatr Scand. 1985 January; 74(1): 114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3885675&dopt=Abstract

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The treatment of cystic fibrosis. A statement by the Committee on Therapy. Author(s): Busey JF, Fenger EP, Hepper NG, Kent DC, Kilburn KH, Matthews LW, Simpson DG, Grzybowski S. Source: Am Rev Respir Dis. 1968 April; 97(4): 730-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4868648&dopt=Abstract

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Therapeutic approach to pancreatic extract-induced hyperuricosuria in cystic fibrosis. Author(s): Nouisa-Arvanitakis S, Stapleton FB, Linshaw MA, Kennedy J. Source: The Journal of Pediatrics. 1977 February; 90(2): 302-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=830926&dopt=Abstract

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Trial of amino acid supplements in cystic fibrosis of the pancreas. Author(s): Darby C, Seakins JW. Source: Archives of Disease in Childhood. 1971 December; 46(250): 866-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=5129189&dopt=Abstract

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Upregulation of cystic fibrosis transmembrane conductance regulator expression by oestrogen and Bak Foong Pill in mouse uteri. Author(s): Rowlands DK, Tsang LL, Cui YG, Chung YW, Chan LN, Liu CQ, James T, Chan HC.

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Source: Cell Biology International. 2001; 25(10): 1033-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11589624&dopt=Abstract ·

Use of famotidine in severe exocrine pancreatic insufficiency with persistent maldigestion on enzymatic replacement therapy. A longterm study in cystic fibrosis. Author(s): Carroccio A, Pardo F, Montalto G, Iapichino L, Soresi M, Averna MR, Iacono G, Notarbartolo A. Source: Digestive Diseases and Sciences. 1992 September; 37(9): 1441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1505293&dopt=Abstract

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Use of nonmedical treatment by cystic fibrosis patients. Author(s): Stern RC, Canda ER, Doershuk CF. Source: The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. 1992 November; 13(7): 612-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1420216&dopt=Abstract

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Vitamin E supplementation in cystic fibrosis. Author(s): Winklhofer-Roob BM. Source: Journal of Pediatric Gastroenterology and Nutrition. 1997 July; 25(1): 120-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9226544&dopt=Abstract

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Energy supplements rich in linoleic acid improve body weight and essential fatty acid status of cystic fibrosis patients. Author(s): Steinkamp G, Demmelmair H, Ruhl-Bagheri I, von der Hardt H, Koletzko B. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 October; 31(4): 418-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11045840&dopt=Abstract

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Enhanced resistance to oxidation of low density lipoproteins and decreased lipid peroxide formation during beta-carotene supplementation in cystic fibrosis. Author(s): Winklhofer-Roob BM, Puhl H, Khoschsorur G, van't Hof MA, Esterbauer H, Shmerling DH.

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Source: Free Radical Biology & Medicine. 1995 May; 18(5): 849-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7797092&dopt=Abstract ·

Epithelial cell specific properties and genetic complementation in a delta F508 cystic fibrosis nasal polyp cell line. Author(s): Kunzelmann K, Lei DC, Eng K, Escobar LC, Koslowsky T, Gruenert DC. Source: In Vitro Cell Dev Biol Anim. 1995 September; 31(8): 617-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8528517&dopt=Abstract

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Essential fatty acid status in cystic fibrosis and the effects of safflower oil supplementation. Author(s): Lloyd-Still JD, Johnson SB, Holman RT. Source: The American Journal of Clinical Nutrition. 1981 January; 34(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7446449&dopt=Abstract

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Evaluation of the forced expiration technique as an adjunct to postural drainage in treatment of cystic fibrosis. Author(s): Pryor JA, Webber BA, Hodson ME, Batten JC. Source: British Medical Journal. 1979 August 18; 2(6187): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=486968&dopt=Abstract

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Evidence that endoplasmic reticulum (ER)-associated degradation of cystic fibrosis transmembrane conductance regulator is linked to retrograde translocation from the ER membrane. Author(s): Xiong X, Chong E, Skach WR. Source: The Journal of Biological Chemistry. 1999 January 29; 274(5): 2616-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9915789&dopt=Abstract

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External ATP and its analogs activate the cystic fibrosis transmembrane conductance regulator by a cyclic AMP-independent mechanism. Author(s): Cantiello HF, Prat AG, Reisin IL, Ercole LB, Abraham EH, Amara JF, Gregory RJ, Ausiello DA.

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Source: The Journal of Biological Chemistry. 1994 April 15; 269(15): 11224-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7512560&dopt=Abstract ·

Extracellular neuraminidase production by a strain of Pseudomonas aeruginosa isolated from cystic fibrosis. Author(s): Leprat R, Michel-Briand Y. Source: Ann Microbiol (Paris). 1980 November-December; 131B(3): 20922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6781392&dopt=Abstract

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Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis. Author(s): Kroesbergen A, Jobsis Q, Bel EH, Hop WC, de Jongste JC. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1999 October; 14(4): 871-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10573235&dopt=Abstract

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Framework for a proactive parent support group: the Syracuse cystic fibrosis model. Author(s): Matloff ET, Zimmerman SJ. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 1996 November-December; 10(6): 264-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9052117&dopt=Abstract

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Granulocyte elastase-mediated proteolysis of alpha 1-antitrypsin in cystic fibrosis bronchopulmonary secretions. Author(s): Cantin A, Bilodeau G, Begin R. Source: Pediatric Pulmonology. 1989; 7(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2788857&dopt=Abstract

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Growing up with chronic illness: the experience of growing up with cystic fibrosis. Author(s): Tracy JP.

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Source: Holistic Nursing Practice. 1997 October; 12(1): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9384068&dopt=Abstract ·

Growing up with cystic fibrosis. Author(s): Helms PJ. Source: Br J Hosp Med. 1993 September 15-October 5; 50(6): 326-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8080484&dopt=Abstract

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Hopkins Teen Central: Assessment of an internet-based support system for children with cystic fibrosis. Author(s): Johnson KB, Ravert RD, Everton A. Source: Pediatrics. 2001 February; 107(2): E24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11158498&dopt=Abstract

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Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment. Author(s): Jobsis Q, Raatgeep HC, Schellekens SL, Kroesbergen A, Hop WC, de Jongste JC. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 July; 16(1): 95100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10933092&dopt=Abstract

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Hyperuricosuria due to high-dose pancreatic extract therapy in cystic fibrosis. Author(s): Stapleton FB, Kennedy J, Nousia-Arvanitakis S, Linshaw MA. Source: The New England Journal of Medicine. 1976 July 29; 295(5): 246-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=934188&dopt=Abstract

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Hypnosis, Theodore Roosevelt, and the patient with cystic fibrosis. Author(s): Anbar RD. Source: Pediatrics. 2000 August; 106(2 Pt 1): 339-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10920161&dopt=Abstract

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Hypovitaminosis D and response to supplementation in older patients with cystic fibrosis. Author(s): Hanly JG, McKenna MJ, Quigley C, Freaney R, Muldowney FP, FitzGerald MX. Source: The Quarterly Journal of Medicine. 1985 July; 56(219): 377-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4095249&dopt=Abstract

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IgE mediated hypersensitivity to pancreatic extract (PE) in parents of cystic fibrosis (CF) children. Author(s): Ganier M, Lieberman P. Source: Clin Allergy. 1979 March; 9(2): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=87285&dopt=Abstract

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IgG proteolytic activity of Pseudomonas aeruginosa in cystic fibrosis. Author(s): Fick RB Jr, Baltimore RS, Squier SU, Reynolds HY. Source: The Journal of Infectious Diseases. 1985 April; 151(4): 589-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3919115&dopt=Abstract

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Impaired resistance to oxidation of low density lipoprotein in cystic fibrosis: improvement during vitamin E supplementation. Author(s): Winklhofer-Roob BM, Ziouzenkova O, Puhl H, Ellemunter H, Greiner P, Muller G, van't Hof MA, Esterbauer H, Shmerling DH. Source: Free Radical Biology & Medicine. 1995 December; 19(6): 725-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8582644&dopt=Abstract

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Improved pulmonary function and exercise tolerance with inspiratory muscle conditioning in children with cystic fibrosis. Author(s): Sawyer EH, Clanton TL. Source: Chest. 1993 November; 104(5): 1490-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8222813&dopt=Abstract

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Influence of antacid and formulation on effectiveness of pancreatic enzyme supplementation in cystic fibrosis. Author(s): Braggion C, Borgo G, Faggionato P, Mastella G.

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Source: Archives of Disease in Childhood. 1987 April; 62(4): 349-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3036018&dopt=Abstract ·

Inhibition of sugar transport by cystic fibrosis plasma. Author(s): Brown GA, Oshin A, Goodchild MC, Anderson CM. Source: Gut. 1971 October; 12(10): 856. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=5166269&dopt=Abstract

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Inspiratory muscle training in patients with cystic fibrosis. Author(s): de Jong W, van Aalderen WM, Kraan J, Koeter GH, van der Schans CP. Source: Respiratory Medicine. 2001 January; 95(1): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11207014&dopt=Abstract

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Intestinal permeability to 51Cr-EDTA and orocecal transit time in cystic fibrosis. Author(s): Escobar H, Perdomo M, Vasconez F, Camarero C, del Olmo MT, Suarez L. Source: Journal of Pediatric Gastroenterology and Nutrition. 1992 February; 14(2): 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1593376&dopt=Abstract

Vocabulary Builder 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] Antibodies: Specific proteins produced by the body's immune system that bind with foreign proteins (antigens). [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly

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contain antioxidants. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Berylliosis: A lung disease resulting from exposure to beryllium metal. [NIH] Beryllium: Beryllium. An element with the atomic symbol Be, atomic number 4, and atomic weight 9.01218. Short exposure to this element can lead to a type of poisoning known as berylliosis. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Cholelithiasis: The presence or formation of gallstones. [EU] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents, characterized in the acute stage by erythema, edema associated with a serous exudate between the cells of the epidermis (spongiosis) and an inflammatory infiltrate in the dermis, oozing and vesiculation, and crusting and scaling; and in the more chronic stages by lichenification or thickening or both, signs of excoriations, and hyperpigmentation or hypopigmentation or both. Atopic dermatitis is the most common type of dermatitis. Called also eczematous dermatitis. [EU] Endogenous: Developing or originating within the organisms or arising from causes within the organism. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fistula: An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body;

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frequently designated according to the organs or parts with which it communicates, as anovaginal, brochocutaneous, hepatopleural, pulmonoperitoneal, rectovaginal, urethrovaginal, and the like. Such passages are frequently created experimentally for the purpose of obtaining body secretions for physiologic study. [EU] Genotype: The entire genetic makeup of an individual. The fundamental constitution of an organism in terms of its hereditary factors. A group of organisms in which each has the same hereditary characteristics. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypoxia: Too little oxygen available to meet the needs of the body’s tissues. [NIH]

Idiopathic: Results from an unknown cause. [NIH] Immunization: Protection from disease by administering vaccines that induce the body to form antibodies against infectious agents. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Keloid: A sharply elevated, irregularly- shaped, progressively enlarging scar due to the formation of excessive amounts of collagen in the corium during connective tissue repair. [EU] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Microorganism: A microscopic organism; those of medical interest include bacteria, viruses, fungi and protozoa. [EU] Microspheres: Small uniformly-sized spherical particles frequently labeled with radioisotopes or various reagents acting as tags or markers. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU]

Perennial: Lasting through the year of for several years. [EU] Peridural: Around or external to the dura mater. [EU] Perioperative: Pertaining to the period extending from the time of hospitalization for surgery to the time of discharge. [EU]

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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] Plasminogen: The inactive precursor of plasmin (=enzyme that catalyses the hydrolysis of peptide bonds at the carbonyl end of lysine or arginine residues). [EU] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]

Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteolytic: 1. pertaining to, characterized by, or promoting proteolysis. 2. an enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Ptosis: 1. prolapse of an organ or part. 2. drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [EU] Radiotherapy: The treatment of disease by ionizing radiation. [EU] 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] Reoperation: A repeat operation for the same condition in the same patient. It includes reoperation for reexamination, reoperation for disease progression or recurrence, or reoperation following operative failure. [NIH] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or

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noun. [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] 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] Transcutaneous: Transdermal. [EU] Urticaria: Pathology: a transient condition of the skin, usually caused by an allergic reaction, characterized by pale or reddened irregular, elevated patches and severe itching; hives. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU]

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CHAPTER 5. PATENTS ON CYSTIC FIBROSIS Overview You can learn about innovations relating to cystic fibrosis by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.23 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

23Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Cystic Fibrosis By performing a patent search focusing on cystic fibrosis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on cystic fibrosis: ·

Compositions and methods for cystic fibrosis therapy Inventor(s): Fischer; Horst (Albany, CA), Illek; Beate (Albany, CA) Assignee(s): Children's Hospital Oakland Research Institute (Oakland, CA) Patent Number: 6,329,422 Date filed: October 16, 1998 Abstract: Compositions and methods for therapy of cystic fibrosis and other conditions are provided. The compositions comprise one or more compounds such as flavones and/or isoflavones capable of stimulating chloride transport in epithelial tissues. Therapeutic methods involve the administration (e.g., orally or via inhalation) of such compositions to a patient afflicted with cystic fibrosis and/or another condition responsive to stimulation of chloride transport. Excerpt(s): The present invention relates generally to the treatment of cystic fibrosis. The invention is more particularly related to compositions comprising one or more compounds such as flavones and/or isoflavones, which may be used to activate chloride transport (i.e., absorption and/or secretion) in epithelial tissues of the airways, the intestine, the pancreas and other exocrine glands, and for cystic fibrosis therapy. ... Cystic fibrosis is a lethal genetic disease afflicting approximately 30,000 individuals in the United States. Approximately 1 in 2500 Caucasians is born with the disease, making it the most common lethal, recessively inherited disease in that population. ... Cystic fibrosis affects the secretory epithelia of a variety of tissues, altering the transport of water, salt and other solutes into and out of the blood stream. In particular, the ability of epithelial cells in the airways, pancreas and other tissues to transport

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chloride ions, and accompanying sodium and water, is severely reduced in cystic fibrosis patients, resulting in respiratory, pancreatic and intestinal ailments. The principle clinical manifestation of cystic fibrosis is the resulting respiratory disease, characterized by airway obstruction due to the presence of a thick mucus that is difficult to clear from airway surfaces. This thickened airway liquid contributes to recurrent bacterial infections and progressively impaired respiration, eventually resulting in death. Web site: http://www.delphion.com/details?pn=US06329422__ ·

Gene therapy for cystic fibrosis Inventor(s): Gregory; Richard J. (Westford, MA), Armentano; Donna (Belmont, MA), Couture; Larry A. (Louisville, CO), Smith; Alan E. (Dover, MA) Assignee(s): Genzyme Corporation (Cambridge, MA) Patent Number: 6,093,567 Date filed: February 10, 1999 Abstract: Gene Therapy vectors, which are especially useful for cystic fibrosis, and methods for using the vectors are disclosed. Excerpt(s): Cystic Fibrosis (CF) is the most common fatal genetic disease in humans (Boat, T. F. et al. in The Metabolic Basis of Inherited Diseases (Scriver, C. R. et al. eds., McGraw-Hill, New York (1989)). Approximately one in every 2,500 infants in the United States is born with the disease. At the present time, there are approximately 30,000 CF patients in the United States. Despite current standard therapy, the median age of survival is only 26 years. Disease of the pulmonary airways is the major cause of morbidity and is responsible for 95% of the mortality. The first manifestation of lung disease is often a cough, followed by progressive dyspnea. Tenacious sputum becomes purulent because of colonization of Staphylococcus and then with Pseudomonas. Chronic bronchitis and bronchiectasis can be partially treated with current therapy, but the course is punctuated by increasingly frequent exacerbations of the pulmonary disease. As the disease progresses, the patient's activity is progressively limited. End-stage lung disease is heralded by increasing hypoxemia, pulmonary hypertension, and cor pulmonale. ... The protein product of the CF associated gene is called the cystic fibrosis transmembrane conductance regulator (CFTR) (Riordan, J. R. et al. (1989) Science 245:1066-1073). CFTR is a protein of approximately 1480 amino acids made up of two repeated elements, each comprising six transmembrane segments and a nucleotide binding domain. The two

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repeats are separated by a large, polar, so-called R-domain containing multiple potential phosphorylation sites. Based on its predicted domain structure, CFTR is a member of a class of related proteins which includes the multi drug resistance (MDR) or P-glycoprotein, bovine adenyl cyclase, the yeast STE6 protein as well as several bacterial amino acid transport proteins (Riordan, J. R. et al. (1989) Science 245:1066-1073; Hyde, S. C. et al. (1990) Nature 346:362-365). Proteins in this group, characteristically, are involved in pumping molecules into or out of cells. ... Sequence analysis of the CFTR gene of CF chromosomes has revealed a variety of mutations (Cutting, G. R. et al. (1990) Nature 346:366-369; Dean, M. et al. (1990) Cell 61:863-870; and Kerem, B-S. et al. (1989) Science 245:1073-1080; Kerem, B-S. et al. (1990) Proc. Natl. Acad Sci. USA 87:84478451). Population studies have indicated that the most common CF mutation, a deletion of the 3 nucleotides that encode phenylalanine at position 508 of the CFTR amino acid sequence (.DELTA.F508), is associated with approximately 70% of the cases of cystic fibrosis. This mutation results in the failure of an epithelial cell chloride channel to respond to cAMP (Frizzell R. A. et al. (1986) Science 233:558-560; Welsh, M. J. (1986) Science 232:1648-1650.; Li, M. et al. (1988) Nature 331:358-360; Quinton, P. M. (1989) Clin. Chem. 35:726-730). In airway cells, this leads to an imbalance in ion and fluid transport. It is widely believed that this causes abnormal mucus secretion, and ultimately results in pulmonary infection and epithelial cell damage. Web site: http://www.delphion.com/details?pn=US06093567__ ·

Antibodies specific for cystic fibrosis transmembrane conductance regulator and uses therefor Inventor(s): Cheng; Seng H. (Bosaton, MA), Marshall; John (Milford, MA), Gregory; Richard J. (Ayer, MA), Rafter; Patrick W. (Natick, MA) Assignee(s): Genzyme Corporation (Cambridge, MA) Patent Number: 5,981,714 Date filed: August 15, 1996 Abstract: Antibodies for binding epitopes of cystic fibrosis transmembrane conductance regulator (CFTR) and hybridomas which produce such antibodies are described. The antibodies of the present invention can be used in a method for detecting CFTR in a biological sample and/or in a method for purifying CFTR from an impure solution. In addition, the present invention includes a method for detecting CFTR in a biological sample from a nonhuman cystic fibrosis knockout animal wherein the the nonhuman cystic fibrosis knockout animal has been

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subjected to human CFTR replacement therapy. Another aspect of the present invention is a method for determining the orientation of CFTR in the membrane of a lipid vesicle. Yet another aspect of the invention is a kit for detecting CFTR in a biological sample. Excerpt(s): Cystic Fibrosis (CF) is the most common fatal genetic disease in humans (Boat, T. et al. Cystic fibrosis. In: The Metabolic Basis of Inherited Disease, C. Scriver, A. Beaudet, W. Sly, and D. Valle, eds. (McGraw Hill, New York, 1989), 2649-2860). Based on both genetic and molecular analysis, a gene associated with CF was isolated as part of 21 individual cDNA clones and its protein product predicted (Kerem, B-S. et al. Science 245:1073-1080 (1989); Riordan, J. et al. Science 245:1066-1073 (1989); Rommens, J. H. et al. Science 245:1059-1065 (1989)). ... The protein product of the CF associated gene is called the cystic fibrosis transmembrane conductance regulator (CFTR) (Riordan, J. et al. Science 245:1066-1073 (1989)). CFTR is a protein of approximately 1480 amino acids made up of two repeated elements, each having six transmembrane segments and a nucleotide binding domain. The two repeats are separated by a large, polar, so-called R-domain containing multiple potential phosphorylation sites. Based on its predicted domain structure, CFTR is a member of a class of related proteins which includes the multidrug resistant (MDR) P-glycoprotein, bovine adenyl cyclase, the yeast STE6 protein as well as several bacterial amino acid transport proteins (Riordan, J. et al. Science 245:1066-1073 (1989); Hyde, S. C. et al. Nature 346:362-365 (1990). Proteins in this group, characteristically, are involved in pumping molecules into or out of cells. ... In order to clarify the role of cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis, further study of the CFTR molecule is needed. The availability of antibodies which bind to defined epitopes which have different locations on the CFTR molecule would greatly facilitate the characterization of the CFTR molecule. In addition, such antibodies would aid in the efficient purification of CFTR from an impure solution and detection of CFTR in biological samples containing CFTR. Web site: http://www.delphion.com/details?pn=US05981714__

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·

Methods for screening for mutations at various positions in the introns and exons of the cystic fibrosis gene Inventor(s): Tsui; Lap-Chee (Toronto, CA), Rommens; Johanna M. (Willowdale, CA), Kerem; Bat-sheva (Jerusalem, IL) Assignee(s): HSC Research Development Corporation (Toronto, CA) Patent Number: 5,981,178 Date filed: June 6, 1995 Abstract: The cystic fibrosis gene and its gene product are described for mutant forms. The genetic and protein information is used in developing DNA diagnosis, protein diagnosis, carrier and patient screening, cloning of the gene and manufacture of the protein, and development of cystic fibrosis affected animals. Excerpt(s): The present invention relates generally to the cystic fibrosis (CF) gene, and, more particularly to the identification, isolation and cloning of the DNA sequence corresponding to mutants of the CF gene, as well as their transcripts, gene products and genetic information at exon/intron boundaries. The present invention also relates to methods of screening for and detection of CF carriers, CF diagnosis, prenatal CF screening and diagnosis, and gene therapy utilizing recombinant technologies and drug therapy using the information derived from the DNA, protein, and the metabolic function of the protein. ... Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder in the Caucasian population. It affects approximately 1 in 2000 live births in North America [Boat et al, The Metabolic Basis of Inherited Disease, 6th ed, pp 2649-2680, McGraw Hill, NY (1989)]. Approximately 1 in 20 persons are carriers of the disease. ... Although the disease was first described in the late 1930's, the basic defect remains unknown. The major symptoms of cystic fibrosis include chronic pulmonary disease, pancreatic exocrine insufficiency, and elevated sweat electrolyte levels. The symptoms are consistent with cystic fibrosis being an exocrine disorder. Although recent advances have been made in the analysis of ion transport across the apical membrane of the epithelium of CF patient cells, it is not clear that the abnormal regulation of chloride channels represents the primary defect in the disease. Given the lack of understanding of the molecular mechanism of the disease, an alternative approach has therefore been taken in an attempt to understand the nature of the molecular defect through direct cloning of the responsible gene on the basis of its chromosomal location. Web site: http://www.delphion.com/details?pn=US05981178__

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·

Macroscopic sweat test for cystic fibrosis Inventor(s): Rubenstein; Ronald Craig (Ardmore, PA), Zeitlin; Pamela Leslie (Baltimore, MD) Assignee(s): Johns Hopkins University (Baltimore, MD) Patent Number: 5,976,499 Date filed: September 4, 1998 Abstract: The present invention relates to methods of diagnosing CF comprising: stimulating sweat production via .beta.-adrenergic pathway, by increasing cAMP production; collecting sweat into a sweat collection device; determining the sweat rate as a function of the weight of the sweat collected; correlating the sweat rate with the functional state of CFTR and/or presence or absence of CF. The invention also relates to methods of screening compounds for treatment of cystic fibrosis. Excerpt(s): This invention relates to methods for discriminating between fully functional, partially functional and non-functional forms of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). More particularly, this invention relates to a macroscopic cyclic-AMP (cAMP)stimulated "sweat rate" test that will discriminate between fully functional, partially functional, and non-functional forms of CFTR. ... Cystic fibrosis (CF) is one of the most common genetic diseases among Caucasians and is a contributing factor in causing suffering among children and adults. CF affects the mucus-producing glands and other exocrine glands in the body. The gene encoding CFTR, the absence of function of which is responsible for causing CF, is located on chromosome 7q. Lack of CFTR function causes abnormal mucus production in the respiratory and gastrointestinal tracts and abnormal sweat gland function. Clinically, CF is characterized by chronic respiratory infections and obstructive lung disease, pancreatic gland insufficiency leading to an inability to digest fats, male infertility and abnormally high levels of electrolytes in the sweat. ... Sweat production is stimulated through two pathways: the cholinergic pathway and by the adrenergic/sympathetic pathway (i.e., fight or flight response). Thus, sweat production can be stimulated by both cholinergic and adrenergic agonists. Collection of cholinergic stimulated sweat, using the cholinergic agonist pilocarpine, and the subsequent measurement of sweat chloride concentration is the basis of a standard diagnostic test for cystic fibrosis (CF), the pilocarpine iontophoresis sweat test. Stimulation of sweat production with pilocarpine leads to initial production of an isotonic secretion in the sweat gland. In non-CF patients, as the secretion traverses the sweat duct, chloride is reabsorbed. This leads to low concentration of chloride in sweat as it appears on the skin. This chloride resorption is

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dependent on the presence of functional CFTR. In CF patients, who lack functional CFTR, the sweat chloride concentration remains high, and distinguishes most, but not all, CF from non-CF patients. However, this technique does not distinguish heterozygote carriers of CFTR mutations from non-carriers, nor does the sweat chloride concentration correlate with disease severity. Furthermore, the pilocarpine iontophoresis sweat test involves the use of a sweat test apparatus consisting of electrodes and a voltage source and the use of specially trained personnel. These methods require the elution of the sweat electrolytes collected on the pads and determination of chloride content of the sweat. While this method remains the "gold standard", it occasionally yields ambiguous results. Therefore, it would be useful to have an alternative method of diagnosing CF. Web site: http://www.delphion.com/details?pn=US05976499__ ·

Genistein for the treatment of cystic fibrosis Inventor(s): Hwang; Tzyh-Chang (Columbia, MO), Smith; Arnold L. (Columbia, MO), Konig; Peter (Columbia, MO), Clarke; Lane L. (Columbia, MO), Price; Elmer M. (Hartsburg, MO), Cohn; Leah A. (Columbia, MO) Assignee(s): The Curators of the University of Missouri (Columbia, MO) Patent Number: 5,948,814 Date filed: February 20, 1998 Abstract: A method of treating cystic fibrosis by generating cystic fibrosis transmembrane conductance regulator (CFTR) function in cells containing mutant CFTR and the therapeutic composition for treatment are described. The method of treatment comprising administering an effective amount of genistein, or genistein analogues and derivatives, to a person afflicted with cystic fibrosis. Excerpt(s): The present invention relates to a therapeutic treatment for cystic fibrosis, particularly to the restoration of chloride channel function caused by mutations in the protein designated Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). ... Cystic fibrosis (CF) is the most common fatal genetic disease among persons of Caucasian origin. The frequency of the disease in this population is approximately 1 in 2500 live births ›Boat et al., 1989!, which translates into a carrier frequency of approximately 1 in 25. CF is associated with a wide-spread defect in the secretory processes of all secretory epithelia. Patients with CF, who rarely live for more than 30 years, exhibit abnormalities in a variety of respiratory, gastrointestinal and genitourinary tract systems, as

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well as elevated sweat electrolyte concentrations. Patients with CF exhibit abnormally viscid mucous secretions that block the airways and the pancreatic ducts. The blockage of the airways and pancreatic ducts are responsible for the two most clinically important manifestations of CF, that being chronic pulmonary infection and pancreatic insufficiency. The damage to the pancreas resulting in over 80% pancreatic insufficiency occurs in utero. ... The relative impermeability of epithelial cell membranes to Cl ions appears to be the primary defect in CF. The molecular basis (the gene) for this defect in Cl ion transport was mapped and identified in 1989 ›Riordan et al, 1989!. The protein product of the CF-associated gene is designated the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The CFTR protein is a single protein of approximately 170 kd and is made up of two repeated elements, each comprising six transmembrane segments and a nucleotide binding domain. The two repeats are separated by a large, polar, domain, designated R, containing multiple potential phosphorylation sites. Web site: http://www.delphion.com/details?pn=US05948814__ ·

Yeast artificial chromosomes containing DNA encoding the cystic fibrosis (CFTR) gene Inventor(s): Anand; Rakesh (Sandbach, GB), Markham; Alexander Fred (Crewe, GB), Smith; John Craig (Nr Knutsford, GB), Anwar; Rashida (Northwich, GB), Riley; John Hamilton (Nr Northwich, GB), Ogilvie; Donald James (Sale, GB), Elvin; Paul (Barnton, GB) Assignee(s): Zeneca Limited (London, GB) Patent Number: 5,939,255 Date filed: May 27, 1994 Abstract: Yeast Artificial Chromosomes (YACS) containing DNA encoding the cystic fibrosis (CFTR) gene are described. The YACs allow detailed analysis of the coding and non-coding regions of the gene and the determination of cystic fibrosis alleles in sample DNA from an individual or individuals. Excerpt(s): The present invention relates to nucleotide sequences and their use in methods for the detection, diagnosis and therapy of genetically inherited disorders. In particular the nucleotide sequences of the invention may be used for the detection of cystic fibrosis alleles. The invention also relates to nucleotide sequences coding for inherited disease associated genes such as cystic fibrosis and to RNA, such as mRNA, and polypeptides such as proteins, derived therefrom. Diagnostic kits are also provided for use in the diagnostic methods of the present

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invention. ... Available methods for the detection of cystic fibrosis are based on linkage studies. In general these comprise the use of labelled probes to detect restriction fragment length polymorphisms in sample genomic DNA. The distinguishing power of the genetic loci detected by the probes mentioned above is limited by the observed degree of polymorphism at such loci. Such probes may therefore identify the same restriction fragment for many individuals and the ability to distinguish between normal and cystic fibrosis alleles in such individuals is no longer possible. A need therefore exists for further and more informative methods of detection and diagnosis. ... Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in the Western world with a carrier frequency of .sup..about. 1/20 and an incidence of 1/1600 live births. The disease is extremely rare in African and Asian populations, although cases have been reported in Japan. Affected patients exhibit elevated sodium chloride secretion in sweat and suffer from a variety of symptoms including bronchiectasis, respiratory failure and pancreatic insufficiency. The nature of the defect causing CF is unknown although it has been shown that sweat gland cells and respiratory epithelial cells from affected patients show a diminished permeability to chloride ions and a defective response to beta adrenergic agents (M J Stutts et al, 1985, PNAS, 82, 6677-6681). More recently, it has been demonstrated that the chloride channel can be activated in CF cells and that in CF patients it is the regulation of the chloride channel that is defective (R. A. Frizzell et al, 1986, Science, 233, 558-560, M. J. Welsh and C. M. Liedtke, 1986, Nature, 322, 467-470). Web site: http://www.delphion.com/details?pn=US05939255__ ·

Cystic fibrosis treatment Inventor(s): Bedwell; David M. (Birmingham, AL) Assignee(s): UAB Research Foundation (Birmingham, AL) Patent Number: 5,840,702 Date filed: March 22, 1996 Abstract: The present invention provides a method of stimulating expression of a functional full-length cystic fibrosis transmembrane conductance regulator protein in an individual in need of such treatment, comprising the step of administering to said individual a pharmacologically effective dose of an aminoglycoside. Also provided is a method of treating cystic fibrosis in an individual in need of such treatment, comprising the step of administering to said individual a therapeutically effective dose of an aminoglycoside. Further provided is a

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method of screening for a drug useful in the treatment of an individual having cystic fibrosis, comprising the step of determining said drug's ability to suppress premature stop mutations in a model of cystic fibrosis and a method of pharmacologically suppressing premature stop mutations in an individual having such mutations, comprising the step of administering to said individual a pharmacologically effective dose of an aminoglycoside. Excerpt(s): The present invention relates generally to the fields of molecular genetics and pharmacotherapy of genetic diseases. More specifically, the present invention relates to a novel treatment for cystic fibrosis using aminoglycoside antibiotics. ... Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). Over 400 distinct mutations in CFTR have been shown to cause CF. The most common of these mutations is the deletion of a phenylalanine at residue 508 (DF508), which is found on 70% of all CF chromosomes. However, severe CF is also caused by a number of different premature stop mutations, which are found on at least 5% of all CF chromosomes. Based upon this frequency, this class of mutations is more common than any single CF-causing mutation other than DF508. Thus, a strategy capable of correcting this entire class of mutations would have a major impact on the survival of a significant fraction of the CF patient population. Although this approach is not expected to restore CFTR function to wild type levels, recent studies have shown that even a small increase in CFTR expression in transgenic mouse models can lead to a significant decrease in the pathology associated with CF (Dorin et al., 1995). In more general terms, premature stop mutations have also been identified in a large number of other human diseases. A recent review catalogued 178 examples of human diseases that resulted from the introduction of premature stop mutations (Atkinson and Martin, 1994). This list included many common diseases such as cancer, diabetes, and hypercholesterolemia that strike a relatively large portion of the general population. As an example, over 25 distinct premature stop mutations that lead to cancer have been identified in the P53 gene alone. Thus, a strategy aimed at suppressing these mutations in CFTR could also be adapted to treat individuals with many other diseases that result from premature stop mutations. ... The prior art is deficient in the lack of effective means of treating cystic fibrosis and other genetic diseases involving premature stop mutations. The present invention fulfills this longstanding need and desire in the art. Web site: http://www.delphion.com/details?pn=US05840702__

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·

Detection of pancreatitis-associated protein for screening for cystic fibrosis Inventor(s): Iovanna; Juan-Lucio (Marseilles, FR), Dagorn; Jean-Charles (Marseilles, FR), Keim; Volker (Heddesheim, DE), Sarles; Jacques (Gemenos, FR) Assignee(s): Institut National de la Sante et de la Recherche Medicale (Paris, FR) Patent Number: 5,834,214 Date filed: August 30, 1995 Abstract: The invention relates to in vitro detection of human pancreatitis-associated protein (hPAP) for the purpose of screening for cystic fibrosis. hPAP is quantitated in a biological sample, preferably blood, and a high value is indicative of pancreatic dysfunction. Immunoassays as rapid, reliable methods for hPAP quantitation are provided as are antibodies for use in the assays and hybridomas for production of monoclonal antibodies preferred for use in the assays. Excerpt(s): Mucoviscidosis, also called "cystic fibrosis" in English is a very frequent genetic disease in certain populations, which is characterized by a global insufficiency of exocrine secretions of the pancreas and the lung and the exocrine glands in general. Clinically, the disease is associated with abnormally viscous secretions, the mucus formed being capable of obstructing the bronchi and causing serious or mortal disorders. ... The mucoviscidosis gene has been localized on human chromosome 7. This gene, called the CFTR gene ("cystic fibrosis transmembrane conductance regulator") shows mutations in different regions in the subjects suffering from mucoviscidosis. Mutations of the same type may be detected on only one of the two chromosomes 7 in subjects called "carriers" but not showing clinical signs of the disease. These persons are heterozygous for the mutation in the CFTR gene. Web site: http://www.delphion.com/details?pn=US05834214__

·

Method of mucociliary clearance in cystic fibrosis patients using alkylaryl polyether alcohol polymers Inventor(s): Ghio; Andrew J. (Durham, NC), Piantadcsi; Claude A. (Durham, NC), Kennedy; Thomas P. (Richmond, VA) Assignee(s): Duke University (Durham, NC) Patent Number: 5,830,436 Date filed: March 30, 1995

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Abstract: A method and medicament for the inhibition of oxidants comprising administering a treatment effective amount of alkylaryl polyether alcohol polymers to a chemical or biologic system in need thereof. Also, a method and medicament for mucociliary clearance, inhibition of cytokine production, and inhibition of interleukin-8 production in cystic fibrosis patients. The method involves administering a treatment effective amount of alkylaryl polyether alcohol polymers to a chemical or biologic system in need thereof. The medicament is preferably administered by aerosolization into the mammalian respiratory system. The medicament may also be applied to the mammalian skin. Preferably, the medicament includes a physiologically acceptable carrier which may be selected from the group consisting of physiologically buffered saline, isotonic saline, normal saline, petrolatum based ointments and U.S.P. cold cream. Excerpt(s): The invention in the present Continuation-in-Part relates, in general, to cystic fibrosis, the most common lethal recessive genetic disease in the United States. Cystic fibrosis is characterized by abundant production in a cystic fibrosis patient of thick, tenacious, purulent airway secretions. These secretions are difficult to clear, even with physiotherapy, and hence, obstruct airways and contribute greatly to the progression of obstructive lung disease by stagnating the inflammatory process within airways. ... More particularly, the invention in the present Continuation-in-Part relates to use of alkylaryl polyether alcohol polymers, particularly tyloxapol, as mucolytic agents for breaking up cystic fibrosis sputum or mucous in patients with cystic fibrosis, as inhibitors of monocyte tumor necrosis factor secretion in patients with cystic fibrosis, and as inhibitors of production of interleukin-8 by patients with cystic fibrosis. ... Also, studies by the present inventors, as described in more detail below, suggest that airway cells in cystic fibrosis patients are at risk of oxidant-mediated injury. The reason is that the leukocytederived enzyme, myeloperoxidase, present in large amounts in the bronchial secretions of cystic fibrosis patients, converts with H.sub.2 O.sub.2 produced by polymorphonuclear leukocytes to HOCl/OCl, the major leukocyte-derived oxidant. Web site: http://www.delphion.com/details?pn=US05830436__

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·

Methods of detecting cystic fibrosis gene by nucleic acid hybridization Inventor(s): Tsui; Lap-Chee (Toronto, CA), Riordan; John R. (Toronto, CA), Collins; Francis S. (Ann Arbor, MI), Rommens; Johanna M. (Willowdale, CA), Iannuzzi; Michael C. (Ann Arbor, MI), Kerem; BatSheva (Toronto, CA), Drumm; Mitchell L. (Ann Arbor, MI), Buchwald; Manuel (Toronto, CA) Assignee(s): HSC Research Development Corporation (Toronto, CA), The Board of Regents, Acting for and on Behalf of The University of (Ann Arbor, MI) Patent Number: 5,776,677 Date filed: June 6, 1995 Abstract: The cystic fibrosis gene and its gene product are described for both the normal and mutant forms. The genetic and protein information is used in developing DNA diagnosis, protein diagnosis, carrier and patient screening, drug and gene therapy, cloning of the gene and manufacture of the protein, and development of cystic fibrosis affected animals. Excerpt(s): The present invention relates generally to the cystic fibrosis (CF) gene, and, more particularly to the identification, isolation and cloning of the DNA sequence corresponding to the normal and mutant CF genes, as well as their transcripts and gene products. The present invention also relates to methods of screening for and detection of CF carriers, CF diagnosis, prenatal CF screening and diagnosis, and gene therapy utilizing recombinant technologies and drug therapy using the information derived from the DNA, protein, and the metabolic function of the cystic fibrosis transmembrane inductance regulator protein (CFTR). ... Although the disease was first described in the late 1930's, the basic defect remains unknown. The major symptoms of cystic fibrosis include chronic pulmonary disease, pancreatic exocrine insufficiency, and elevated sweat electrolyte levels. The symptoms are consistent with cystic fibrosis being an exocrine disorder. Although recent advances have been made in the analysis of ion transport across the apical membrane of the epithelium of CF patient cells, it is not clear that the abnormal regulation of chloride channels represents the primary defect in the disease. Given the lack of understanding of the molecular mechanism of the disease, an alternative approach has therefore been taken in an attempt to understand the nature of the molecular defect through direct cloning of the responsible gene an the basis of its chromosomal location. ... However, there is no clear phenotype that directs an approach to the exact nature of the genetic basis of the disease, or that allows for an identification of the cystic fibrosis gene. The nature of the CF defect in

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relation to the population genetics data has not been readily apparent. Both the prevalence of the disease and the clinical heterogeneity have been explained by several different mechanisms: high mutation rate, heterozygote advantage, genetic drift, multiple loci, and reproductive compensation. Web site: http://www.delphion.com/details?pn=US05776677__

Patent Applications on Cystic Fibrosis As of December 2000, U.S. patent applications are open to public viewing.24 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years). The following patent applications have been filed since December 2000 relating to cystic fibrosis: ·

Compositions for treating cystic fibrosis Inventor(s): Budny, John A. ; (Westlake Village, CA), Budny, Matthew J. ; (Westlake Village, CA) Correspondence: Colin P Abrahams; 5850 Canoga Avenue; Suite 400; Woodland Hills; CA; 91367 Patent Application Number: 20020022005 Date filed: June 6, 2001 Abstract: A composition for degrading biofilm structure associated with cystic fibrosis and the debris associated therewith comprises an enzyme selected for its ability to dismantle the biofilm structure, and an anchor molecule coupled to an enzyme to form an enzyme-anchor complex. The anchor molecule is selected for its ability to attach to a surface on or proximal the biofilm structure. The attachment to the surface permits prolonged retention time of the enzyme-anchor complex where the biofilm structure and associated debris are present. Excerpt(s): Cystic fibrosis, a genetically inherited disease, is caused by the mutation of a gene that produces an electrolyte transfer protein. The consequence of the mutation affects a multitude of organ systems. However, the tissues that are most directly affected are those that secrete mucus or have mucus membranes. Serious adverse consequences occur with tissues that are associated with the respiratory system i.e. lungs and airway passage tissues. In response to the genetic defect, the host produces secretions to counteract the ionic imbalance. These secretions in response to the disease allow opportunistic infections to develop which

24

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

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causes additional fluid and mucus to infiltrate the respiratory system from the host. The additional fluid from the host in response to the infection is under the influence of the immune system. Finally, the infectious bacteria and the associated bacterial biofilm add additional mucus and fluid at the site. Furthermore, the principal bacterial pathogen associated with the opportunistic infection is Pseudomonas aeruginosa, which often mutates to a mucoid form that is a prolific producer of alginate biofilm, which further exacerbates the disease condition. The result is an accumulation of copious amount of mucus, fluid and biofilm material which affects not only the respiratory system, but the entire host. ... The current treatment of cystic fibrosis involves a dual approach to: 1) promote and facilitate the removal of mucus and secretions from the respiratory tract and; 2) control the infection that is associated with the disease. The infection, with the bacteria's production of a biofilm, obstructs the host's defenses, shields the bacteria from the killing action of antibiotics and increases the viscosity of the mucus, making it increasingly difficult for the patient to expectorate the interfering mucus. ... Based on work done in the 1950s and 1960s and summarized by Skak et al. [Proc. Natl. Acad. Sci. 87, 9188-9192(1990)], the viscosity of the sputum from cystic fibrosis patients was reduced when the sputum was treated with the enzyme DNase. Consequently, a less viscous, easier flowing mucus is more readily expectorated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compositions and methods for the treatment of cystic fibrosis Inventor(s): Faller, Douglas V. ; (Weston, MA), Perrine, Susan P. ; (Weston, MA), Stamatoyannopoulos, George ; (Seattle, WA) Correspondence: James Remenick; Intellectual Property Department; Brobeck, Phleger & Harrison LLP; 1333 H Street, N.W., Suite 800; Washington; DC; 20005; US Patent Application Number: 20010034367 Date filed: February 15, 2001 Abstract: The invention is directed to novel pharmaceutical compositions comprising chemicals agents that are useful in the treatment and prevention of cystic fibrosis and the prevention of signs and symptoms of this disease. These pharmaceutical compositions are surprisingly successful in the treatment disorders related to cystic fibrosis including disorders of blood production. Many of these compositions of the invention are even more effective when administered to a patient in pulses. Pulse therapy is not a form of discontinuous administration of the

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same amount of a composition over time, but comprises administration of the same dose of the composition at a reduced frequency or administration of reduced doses. Excerpt(s): The invention relates to pharmaceutically acceptable compositions for administration to humans to treat cystic fibrosis and also to methods for effectively utilizing these compositions. ... Cystic fibrosis (CF) is a systemic disorder that results when mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an apical membrane glycoprotein, lead to a reduction in apical membrane chloride transport. CFTR is a cAMP-dependent chloride channel that regulates fluid composition in the respiratory and gastrointestinal tracts. CF is a heritable disease that follows an autosomal recessive pattern of transmission. It is the most common invariably lethal genetic disease in the United States, with frequency among Caucasians being one in two thousand. One in twenty are carriers of the defective gene. CF is characterized by abnormal endocrine and exocrine gland function. In CF, unusually thick mucus leads chronic pulmonary disease and respiratory infections, insufficient pancreatic and digestive function, and abnormally concentrated sweat. Seventy percent of the mutant CFTR alleles in the Caucasian population result from deletion of phenylalanine at position 508 (.DELTA.F508-CFTR), the result of a three base pair deletion in the genetic code. Other mutations have also been described and many may exist. The .DELTA.F508-CFTR mutation results in a CFTR protein capable of conducting chloride, but absent from the plasma membrane because of aberrant intracellular processing. Under usual conditions (37.degree. C.), the .DELTA.F508-CFTR protein is retained in the endoplasmic reticulum (ER), by prolonged association with the ER chaperones, including calnexin and hsp70. The retained CFTR protein is then targeted for degradation by the ubiquitin proteasome pathway. Over expression of .DELTA.F508-CFTR can result in .DELTA.F508-CFTR protein appearing at the cell surface, and this protein is functional once it reaches the cell surface. The .DELTA.F508 "trafficking" block is also reversible by incubation of cultured CF epithelial cells at reduced temperatures (2527.degree. C.). Lowered temperature results in the appearance of CFTR protein and channel activity at the cell surface, suggesting an intrinsic thermodynamic instability in .DELTA.F508-CFTR at 37.degree. C. that leads to recognition of the mutant protein by the ER quality control mechanism, prevents further trafficking, and results in protein degradation. High concentrations of glycerol (1 M or 10%), a protein stabilizing agent or chemical chaperone, also appears to facilitate movement of .DELTA.F508-CFTR from the ER to the plasma membrane. ... Gene therapy for cystic fibrosis has been attempted, but has not been successful to date for a number of reasons, including problems with

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delivery of the gene to airway cells, insufficient levels of gene expression, inadequate duration of gene expression, and toxicity of the gene therapy preparations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with cystic fibrosis, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “cystic fibrosis” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on cystic fibrosis. You can also use this procedure to view pending patent applications concerning cystic fibrosis. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Aberrant: Wandering or deviating from the usual or normal course. [EU] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Cholinergic: Resembling acetylcholine in pharmacological stimulated by or releasing acetylcholine or a related compound. [EU]

action;

Epitopes: Sites on an antigen that interact with specific antibodies. [NIH]

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Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH]

Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH]

Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of

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the 2 position. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, ...): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH]

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] 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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU]

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Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: Process of exchanging oxygen from the air for carbon dioxide from the body; includes the mechanical process of breathing, gas exchange, and oxygen and carbon dioxide transport to and from the cells. [NIH] Saline: Salty; of the nature of a salt; containing a salt or salts. [EU] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH]

Sympathetic: 1. pertaining to, caused by, or exhibiting sympathy. 2. a sympathetic nerve or the sympathetic nervous system. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU]

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CHAPTER 6. BOOKS ON CYSTIC FIBROSIS Overview This chapter provides bibliographic book references relating to cystic fibrosis. You have many options to locate books on cystic fibrosis. 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 parents, however, prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on cystic fibrosis 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: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “cystic fibrosis” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on cystic fibrosis: ·

Exercise and Children's Health Source: Champaign, IL, Human Kinetics Books, 356 p., 1990.

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Contact: Human Kinetics Books, P.O. Box 5076, Champaign, IL 618255076. (800) DIAL-HKP. (800) 334-3665 (in Illinois). Summary: Exercise and Children's Health provides pediatric cardiologists, pediatricians, family practitioners, and other primary care providers with a guide on improving and maintaining children's health through exercise. The text offers practical guidelines for exercise prescription and physical fitness for healthy children and for children with special health concerns such as obesity, heart disease, asthma, cystic fibrosis, diabetes, and seizure disorders. The book contains three parts: (1) Developmental Exercise Physiology: The Physiological basis of Physical Fitness in Children; (2) Influence of Exercise on Health; and (3) Strategies for Improving Exercise Habits on Children. Part one provides basic information regarding children's physiological responses to exercise, emphasizing developmental changes that occur during the growing years. Part two reviews the scientific grounds for promoting exercise as a beneficial health measure. Part three provides specific strategies for increasing physical activity in children through both structured and unsupervised programs; practical guidelines give physicians and other professionals useful materials for prescribing exercise programs for young patients. 38 figures, 12 tables, 775 references. ·

Chronic and disabling disorders Source: Philadelphia, PA: Hanley and Belfus. 1994. 169 pp. Contact: Available from Hanley and Belfus, 210 South 13th Street, Philadelphia, PA 19107. Telephone: (215) 546-4995. $66.00 for yearly subscription to three issues in the series; single issues available. Summary: This edition addresses both general issues of importance in health care for adolescents with special health needs and specific chronic conditions. The first set of articles focuses on the epidemiology of chronic illness in adolescence and developmental, educational, and health care delivery issues. The second set discusses specific chronic conditions that are prevalent in the adolescent population (i.e., deafness, cancer, traumatic brain injury, and sickle cell disease) or that have had recent advances in management (i.e., cystic fibrosis, organ transplants, and spinal cord injuries).

·

Listen, my child has a lot of living to do Source: New York, NY: Oxford University Press. 1990. 192 pp. Contact: Available from Oxford University Press, 2001 Evans Road, Cary, NC 27513. Telephone: (800) 451-7556 or (919) 677-0977 / fax: (919) 6771303. $15.95 paper, $45.00 hardbound.

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Summary: This book discusses the partnership between parents and professionals in caring for children with life-threatening conditions. It describes initiatives taken in England to redress deficiencies in providing care to terminally ill children and their families so as to provide a comprehensive, flexible, and compassionate national network of care. It covers domiciliary and respite hospice care, specialist organ/system failure and parent self-help groups (congenital heart disease, infant deaths, children with AIDS, cystic fibrosis, and mucopolysaccharide disease), education of children and of professionals, and bereavement.

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). The following have been recently listed with online booksellers as relating to cystic fibrosis (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

A Parent's Guide to Cystic Fibrosis (University of Minnesota Guides to Birth and Childhood Disorder) by Burton L. Shapiro, Ralph C. Heussner (1991); ISBN: 0816614881; http://www.amazon.com/exec/obidos/ASIN/0816614881/icongroupin terna

·

Cellular and Molecular Basis of Cystic Fibrosis by G. Mastella (Editor) (1988); ISBN: 0911302638; http://www.amazon.com/exec/obidos/ASIN/0911302638/icongroupin terna

·

Clinical Ecology of Cystic Fibrosis : Proceedings of the 18th European Cystic Fibrosis Conference, Madrid, 21-26 May 1993 (International Congress, No) by H. Escobar, et al (1993); ISBN: 0444816704; http://www.amazon.com/exec/obidos/ASIN/0444816704/icongroupin terna

·

Current Problems and New Trends in Cystic Fibrosis by M. Schoeni (Editor) (1981); ISBN: 3805534175; http://www.amazon.com/exec/obidos/ASIN/3805534175/icongroupin terna

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·

Cystic Fibrosis by Michael E. Fritz (1973); ISBN: 0842271333; http://www.amazon.com/exec/obidos/ASIN/0842271333/icongroupin terna

·

Cystic Fibrosis by Lynn M. Taussig (Editor) (1984); ISBN: 0865771146; http://www.amazon.com/exec/obidos/ASIN/0865771146/icongroupin terna

·

Cystic Fibrosis (1993); ISBN: 019262024X; http://www.amazon.com/exec/obidos/ASIN/019262024X/icongroupi nterna

·

Cystic Fibrosis (Molecular Medicine) by Peter Goodfellow (Editor) (1989); ISBN: 0192618350; http://www.amazon.com/exec/obidos/ASIN/0192618350/icongroupin terna

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Cystic Fibrosis : Directory of Authors of New Medical and Scientific Reviews With Subject Index (1996); ISBN: 0788310437; http://www.amazon.com/exec/obidos/ASIN/0788310437/icongroupin terna

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Cystic Fibrosis : Directory of Authors of New Medical and Scientific Reviews With Subject Index (1996); ISBN: 0788310429; http://www.amazon.com/exec/obidos/ASIN/0788310429/icongroupin terna

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Cystic Fibrosis : Infection, Immunopathology, and Host Response (Allergy and Immunology : Clinical and Experimental Progress) by Richard B. Moss (Editor) (1990); ISBN: 0896031926; http://www.amazon.com/exec/obidos/ASIN/0896031926/icongroupin terna

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Cystic Fibrosis : Nutritional and Intestinal Disorders by Ross W. Shepherd, Geoffrey J. Cleghorn (1989); ISBN: 0849369541; http://www.amazon.com/exec/obidos/ASIN/0849369541/icongroupin terna

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Cystic Fibrosis and DNA Tests: Implications of Carrier Screening (1992); ISBN: 0160379865; http://www.amazon.com/exec/obidos/ASIN/0160379865/icongroupin terna

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Cystic Fibrosis of the Pancreas by Anderson (1976); ISBN: 0397603894; http://www.amazon.com/exec/obidos/ASIN/0397603894/icongroupin terna

·

Cystic Fibrosis Pulmonary Infections : Lessons from Around the World (Respiratory Pharmacology and Pharmacotherapy) by A. Bauernfeind

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(Editor), et al (1996); ISBN: 081765027X; http://www.amazon.com/exec/obidos/ASIN/081765027X/icongroupi nterna ·

Cystic Fibrosis Pulmonary Infections: Lessons from Around the World (1996); ISBN: 376435027X; http://www.amazon.com/exec/obidos/ASIN/376435027X/icongroupi nterna

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Cystic Fibrosis, Basic and Clinical Research : Proceedings of the 17th Annual Meeting of the European Working Group for Cystic Fibrosis, Copenhagen, by Niels Hoiby, Svend Stenvang Pedersen (Editor) (1993); ISBN: 0444813780; http://www.amazon.com/exec/obidos/ASIN/0444813780/icongroupin terna

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Cystic Fibrosis; Index to Modern Information by Jonathon Greer (1988); ISBN: 0881649236; http://www.amazon.com/exec/obidos/ASIN/0881649236/icongroupin terna

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Family Nursing : The Case of Cystic Fibrosis by Dorothy A. Whyte (1994); ISBN: 1856285243; http://www.amazon.com/exec/obidos/ASIN/1856285243/icongroupin terna

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Fluid and Electrolyte Abnormalities in Exocrine Glands in Cystic Fibrosis by P. M. Quinton (Editor) (1982); ISBN: 091130245X; http://www.amazon.com/exec/obidos/ASIN/091130245X/icongroupi nterna

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Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey (1992); ISBN: 0160380936; http://www.amazon.com/exec/obidos/ASIN/0160380936/icongroupin terna

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Genetic Studies of the Cystic Fibrosis Transmembrane Conductance Regulator Gene in Belgian Cf Patients (Acta Biomedica Lovaniensia , No 110) by Harry Cuppens (1995); ISBN: 9061866820; http://www.amazon.com/exec/obidos/ASIN/9061866820/icongroupin terna

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Genetics and Epithelial Cell Dysfunction in Cystic Fibrosis (1988); ISBN: 0845151045; http://www.amazon.com/exec/obidos/ASIN/0845151045/icongroupin terna

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Genetics and Epithelial Cell Dysfunction in Cystic Fibrosis : Proceedings (Progress in Clinical and Biological Research, Vol 254) by

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John R. Riordan (Editor) (1988); ISBN: 0471610429; http://www.amazon.com/exec/obidos/ASIN/0471610429/icongroupin terna ·

Immunological Aspects of Cystic Fibrosis (CRC Series in Immunology and Lymphoid Cell Biology) by Emmanuel Shapira, Gregory B. Wilson (Editor) (1985); ISBN: 084936373X; http://www.amazon.com/exec/obidos/ASIN/084936373X/icongroupi nterna

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Inhalation Therapy: Roche and Genentech Symposium European Cystic Fibrosis Conference, Paris, June 1994 (Respiration, Vol 62, Suppl 1) by Ch. Koch, E. Puchelle (Editor) (1995); ISBN: 3805561644; http://www.amazon.com/exec/obidos/ASIN/3805561644/icongroupin terna

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My Life in My Hands : Living on With Cystic Fibrosis by Doug Lab (1990); ISBN: 0962921602; http://www.amazon.com/exec/obidos/ASIN/0962921602/icongroupin terna

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Psychosocial Aspects of Cystic Fibrosis : A Model for Chronic Lung Disease by Paul Patterson (1973); ISBN: 0930194330; http://www.amazon.com/exec/obidos/ASIN/0930194330/icongroupin terna

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Psychosocial Aspects of Cystic Fibrosis; A Model for Chronic Lung Disease. (1973); ISBN: 0882387022; http://www.amazon.com/exec/obidos/ASIN/0882387022/icongroupin terna

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Readings in Cystic Fibrosis by Special Learning Corporation Staff (1984); ISBN: 089568411X; http://www.amazon.com/exec/obidos/ASIN/089568411X/icongroupi nterna

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The Identification of the Cf (Advances in Experimental Medicine and Biology, 290) by Lap-Chee Tsui, et al (1991); ISBN: 0306439093; http://www.amazon.com/exec/obidos/ASIN/0306439093/icongroupin terna

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

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LOCATORplus.” Once you are in the search area, simply type “cystic fibrosis” (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 ·

ABC transporters: biochemical, cellular, and molecular aspects. Author: edited by Suresh V. Ambudkar, Michael M. Gottesman; Year: 1998; San Diego: Academic Press, c1998; ISBN: 0121821935 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0121821935/icongroupin terna

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Cost of care for individuals with cystic fibrosis in Alberta: a regression approach to determining important cost drivers. Author: Jeffrey A. Johnson ... [et al.]; Year: 1999; Edmonton, Alta.: Institute of Health Economics, [1999]

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Cystic fibrosis: a guide for patient and family. Author: David M. Orenstein; Year: 1997; Philadelphia: Lippincott-Raven, c1997; ISBN: 0397516533 http://www.amazon.com/exec/obidos/ASIN/0397516533/icongroupin terna

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Cystic fibrosis: medical care. Author: David M. Orenstein, Beryl J. Rosenstein, Robert C. Stern; Year: 2000; Philadelphia: Lippincott Williams & Wilkins, c2000; ISBN: 0781717981 http://www.amazon.com/exec/obidos/ASIN/0781717981/icongroupin terna

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Cystic fibrosis care: quality of care guidelines: recommendations of the Victorian Clinical Standards Advisory Group on Cystic Fibrosis. Author: Orenstein, David M., 1945-; Year: 1999; Southbank, Vic.: Victoria, c1999

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Cystic fibrosis handbook. Author: Cystic Fibrosis Association of Victoria Inc; Year: 1997; South Melbourne, Vic.: The Association, c1997; ISBN: 0646319620

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.

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Cystic fibrosis in adults. Author: editors, James R. Yankaskas, Michael R. Knowles; foreword by Thomas F. Boat; Year: 1999; Philadelphia: Lippincott-Raven, c1999; ISBN: 0781710111 http://www.amazon.com/exec/obidos/ASIN/0781710111/icongroupin terna

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Cystic fibrosis. Author: by Judy Monroe; Year: 2001; Mankato, Minn.: LifeMatters, c2001; ISBN: 0736810269 http://www.amazon.com/exec/obidos/ASIN/0736810269/icongroupin terna

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Cystic fibrosis. Author: edited by Margaret E. Hodson, Duncan M. Geddes; Year: 2000; London: Arnold; New York: Oxford University Press, 2000; ISBN: 0340742089 http://www.amazon.com/exec/obidos/ASIN/0340742089/icongroupin terna

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Cystic fibrosis. Author: edited by Dennis Shale; Year: 1996; London: BMJ Pub. Group, 1996; ISBN: 072790826X http://www.amazon.com/exec/obidos/ASIN/072790826X/icongroupi nterna

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Dépistage néonatal de la mucoviscidose: actes du congrès international, Caen, 10-11 septembre 1998 = Neonatal screening for cystic fibrosis: proceedings of the international conference Caen, september 10-11 1998. Author: publiés sous la direction de George; Year: 1999; Caen: Presses universitaires de Caen, 1999; ISBN: 2841330753

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Development of a disease-specific health-related quality of life instrument for people with cystic fibrosis. Author: Melinda A. Connolly ... [et al.]; Year: 2000; Edmonton, Alta.: Institute of Health Economics, [2000]

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DNase for cystic fibrosis patients with mild to moderate lung disease. Author: F. Christopher, D. Chase, R. Milne; Year: 1999; Bristol, UK: South and West Regional Health Authority, 1999

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Genetic testing for cystic fibrosis: January 1989 through February 1997: 1224 citations. Author: prepared by Cynthia B. Love, Elizabeth J. Thomson; Year: 1997; Bethesda, Md: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of Medicine, Reference Section, 1997

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Guidelines for the diagnosis and management of cystic fibrosis. Author: prepared by Fernando A. de Abreu e Silva, John A. Dodge; Year: 1996; [Geneva]: World Health Organization, Human Genetics Programme, c1996

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Implementation of cystic fibrosis services in developing countries: report of a Joint WHO. Author: International Cystic Fibrosis

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(Mucoviscidosis) Association Meeting, Manama, Bahrain, 18019 November 1995; Year: 1995; [Geneva]: World Health Organization, Human Genetics Programme, Division of Noncommunicable Diseases, 1995 ·

In the shadow of illness: parents and siblings of the chronically ill child. Author: by Myra Bluebond-Langner; Year: 1996; Princeton, N.J.: Princeton University Press, c1996; ISBN: 0691027838 (cl: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0691027838/icongroupin terna

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Living-donor lobar lung transplantation for end-stage pulmonary failure in cystic fibrosis. Author: ECRI; Year: 2001; Plymouth Meeting, PA: ECRI, c2001

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Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy. Author: Mary Ann G. Cutter ... [et al.]; Year: 1992; Colorado Springs, CO: BSCS, the Colorado College; Chicago, IL: American Medical Association, 1992

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Neonatal screening for cystic fibrosis. Author: Mateu Serra-Prat; Year: 2000; Barcelona: CAHTA, [2000]

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Preconception and prenatal carrier screening for cystic fibrosis: clinical and laboratory guidelines. Author: American College of Obstetricians and Gynecologists, American College of Medical Genetics; Year: 2001; Washington, DC: American College of Obstetricians and Gynecologists, c2001; ISBN: 0915473747 (alk. paper)

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Psychosocial aspects of cystic fibrosis. Author: edited by Myra Bluebond-Langner, Bryan Lask, Denise B. Angst; Year: 2001; London: Arnold; New York; Oxford University Press, 2001; ISBN: 0340758910 http://www.amazon.com/exec/obidos/ASIN/0340758910/icongroupin terna

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Sweat testing: sample collection and quantitative analysis (approved guideline). Author: V. A. LeGrys ... [et al.]; Year: 1994; Villanova, PA: NCCLS, 1994; ISBN: 1562382608

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Sweat testing: sample collection and quantitative analysis: approved guideline. Author: Vickie A. LeGrys ... [et. al.]; Year: 2000; Wayne, Pa.: NCCLS, c2000; ISBN: 1562384074

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Treatment of the hospitalized cystic fibrosis patient. Author: edited by David M. Orenstein, Robert C. Stern; Year: 1998; New York: M. Dekker, c1998; ISBN: 0824795008 (hardcover: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0824795008/icongroupin terna

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Chapters on Cystic Fibrosis Frequently, cystic fibrosis will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with cystic fibrosis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and cystic fibrosis 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 “cystic fibrosis” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on cystic fibrosis: ·

Malabsorption Syndromes Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 75-84. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 8746418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter from a gastroenterology text addresses malabsorption syndromes. Malabsorption means failure to absorb one or more dietary constituents, often because of a defect in the mucosa of the small intestine (celiac disease, lactase deficiency). Common symptoms of the malabsorption syndrome include diarrhea, weight loss, flatulence, and bloating. The hallmark of malabsorption is steatorrhea with diarrhea, but approximately 10 percent of patients may have isolated steatorrhea without diarrhea. The authors outline a method for evaluating each organ system involved in the malabsorption syndrome, including the stomach, liver, pancreas, and small intestine. Specific tests for evaluating both structure and function are covered, as are diagnostic tests and treatment options for each organ system disorder. The causes for malabsorption include postsurgical complications and Zollinger-Ellison syndrome (stomach); cholestatic liver disease (liver); chronic pancreatitis and cystic fibrosis (pancreas); and pancreatic carcinoma, kwashiorkor, and deficiency of trypsinogen or enterokinase; gluten-sensitive enteropathy, Crohn's disease, Whipple's disease, lactase deficiency, eosinophilic gastroenteritis, tropical sprue, short bowel syndrome, bacterial overgrowth, AIDS, abetalipoproteinemia, radiation enteritis, diabetes mellitus, and ischemia (small intestine). One chart lists tests used to distinguish maldigestion from malabsorption. The first step in the

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management of patients with steatorrhea is a low fat diet. 9 tables. 11 references. (AA-M). ·

Long-Chain-Triglyceride-Restricted, Medium-Chain Triglyceride Diet Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 425-429. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 877-1600 or (312) 899-0040. Fax (312) 899-4899. PRICE: $59.95 for members, $70.00 for nonmembers. ISBN: 0880911530. Summary: This section outlining a long-chain triglyceride (LCT) restricted, medium-chain triglyceride (MCT) diet is from a manual that serves as a nutrition care guide for dietetics professionals, physicians, nurses, and other health professionals. The manual integrates current knowledge of nutrition, medical science, and food to set forth recommendations for healthy individuals and those for whom medical nutrition therapy (MNT) is indicated. The LCT restricted, MCT diet is used to improved digestion, absorption, or utilization of conventional dietary fat by substituting MCTs for LCTs. Some medical conditions for which this diet is considered clinically useful are intestinal resection, celiac sprue, deficient bile salts, ileal disease with steatorrhea, Whipple's disease, pancreatic insufficiency, cystic fibrosis, liver disease, and biliary obstruction. The text outlines the purpose, use, modifications, and adequacy of the diet. The section also notes the related physiology, noting how LCTs may cause malabsorption and steatorrhea. A brief sample menu is included. 2 tables. 10 references. (AA-M).

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Fat-Modified Diets for Malabsorption Syndromes Source: in Cataldo, C.B., DeBruyne, L.K., and Whitney, E.N. Nutrition and Diet Therapy: Principles and Practice. 4th ed. St. Paul, MN: West Publishing Company. 1995. p. 617-634. Contact: Available from West Publishing. 620 Opperman Drive, P.O. Box 64779, St. Paul, MN 55164. (800) 340-9378 or (612) 687-7000. PRICE: $58.25. ISBN: 0314044485. Summary: This chapter, from a text on nutrition and diet therapy, examines fat-modified diets designed to help solve nutrition problems caused by fat malabsorption. Such diets restrict total fat, without regard to the type. Topics include treatments for malabsorption syndromes; pancreatitis; cystic fibrosis; Crohn's disease; ulcerative colitis; bacterial overgrowth in the small intestine; and short bowel syndrome. The chapter concludes with an illustrative case study, a nutrition assessment

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section, and a section on nutrition and diagnostic tests. Also included are study questions and clinical application questions for readers to use in reviewing the material. 4 figures. 4 tables. ·

Nutrition and Disorders of the Lower GI Tract Source: in Whitney, E.N., Cataldo, C.B., and Rolfes, S.R. Understanding Normal and Clinical Nutrition. 4th ed. St. Paul, MN: West Publishing Company. 1994. p. 796-821. Contact: Available from West Publishing. 620 Opperman Drive, St. Paul, MN 55164. (800) 340-9378 or (612) 687-7000. PRICE: $67.00. ISBN: 0314041788. Summary: This chapter on nutrition and disorders of the lower gastrointestinal (GI) tract is from an introductory medical textbook on nutrition. Topics include severe diarrhea and irritable bowel syndrome (IBS); the nutritional consequences of malabsorption; malabsorption syndromes, including pancreatitis, cystic fibrosis, Crohn's disease, ulcerative colitis, celiac disease, and malabsorption caused by intestinal surgery; diverticular disease of the colon; and nutrition assessment. The chapter concludes with study questions, clinical application questions, and a 'highlight' section addressing therapeutic diets. The latter section includes three illustrative case reports. 3 figures. 6 tables. 16 references. (AA-M).

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Food Intolerance Source: in Gerber, J.M. Handbook of Preventive and Therapeutic Nutrition. Frederick, MD: Aspen Publishers, Inc. 1993. p. 42-45. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21701-9782. (800) 638-8437 or (301) 417-7500. PRICE: $34. ISBN: 0834203189. Summary: This chapter, from a handbook of preventive and therapeutic nutrition, provides an overview about food intolerance. Sections include maldigestion disorders; gastrointestinal disease, including celiac sprue, cystic fibrosis, and cholecystitis; metabolic defects, including phenylketonuria, and galactosemia; psychologic reactions; natural substances causing food intolerance, including phenylethylamine, tyramine, histamine, and histamine-releasing agents; food additives causing food intolerance, including tartrazine (yellow No. 5), benzoic acid, sulfites, and monosodium glutamate (MSG); and microorganism contamination causing food intolerance, including proteus and gonyaulax catenella. In each section, brief information is presented on the type of reaction common to the agent described.

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Gastrointestinal and Pancreatic Disease Source: in Gottschlich, M.M.; Matarese, L.E.; and Shronts, E.P., eds. Nutrition Support Dietetics: Core Curriculum. 2nd ed. Silver Spring, MD: American Society of Parenteral and Enteral Nutrition. 1993. p. 275-310. Contact: Available from American Society of Parenteral and Enteral Nutrition (A.S.P.E.N.). 8630 Fenton Street, Suite 412, Silver Spring, MD 20910. (301) 587-6315. PRICE: $50 for A.S.P.E.N. members; $77 for nonmembers. Summary: This chapter, from a textbook of nutrition support dietetics, presents a detailed outline describing the nutritional support for gastrointestinal and pancreatic disease. Topics include the normal function of the gastrointestinal (GI) tract; specific gut fuels, including glutamine, protein, fiber, and short-chain fatty acids; common GI disorders, including esophageal perforation, esophageal obstruction, esophageal varices, esophageal resection, gastric surgery, inflammatory bowel disease, and malabsorption; short bowel syndrome (SBS); enteric fistulas; chylous ascites; and pancreatic disorders, including pancreatitis, and cystic fibrosis. For each disease or condition, the author covers nutritional management, including parenteral or enteral nutrition, physiology, pharmacologic treatment, and complications. The chapter concludes with a list of self-assessment questions. 44 references.

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Toxigenic Diarrheas, Congenital Diarrheas, and Cystic Fibrosis: Disorders of Intestinal Ion Transport Source: in Hoffman, J.F. and De Weer, P., eds. Annual Review of Physiology. Palo Alto, CA: Annual Reviews Inc. 1993. Volume 55: 631655. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. E-mail: [email protected]. PRICE: $46.00. ISBN: 0824303555. ISSN: 00664278. Individual chapter reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. Base price $13.50 per article. Summary: This entry from the Annual Review of Physiology discusses the pathophysiology of enterotoxic diarrheas, congenital diarrheas, and cystic fibrosis (CF). The authors begin with a brief summary of the ion transport properties of the intestine as they relate to the active secretion of electrolytes. Other topics include Vibrio Cholerae enterotoxins, including the cholera toxin and the enteric nervous system; heat-stable Escherichia Coli enterotoxin and guanylin; congenital defects of intestinal

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electrolyte transport; and directions for future research. 3 figures. 128 references. ·

Congenital Genetic Disorders and Syndromes Source: in Pinkham, J.R., et al., eds. Pediatric Dentistry: Infancy Through Adolescence. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 225-250. Contact: Available from W.B. Saunders Company. Book Orders Fulfillment Department, Harcourt Health Sciences, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522. Website: www.wbsaunders.com. PRICE: $69.00 plus shipping and handling. ISBN: 0721682383. Summary: This chapter on congenital genetic disorders and syndromes is from a textbook on pediatric dentistry. The author notes that, although many of these disorders are not preventable or curable, early detection may allow significantly improved health care for the affected individual and improved family planning. Topics include inheritance patterns, including dominant, recessive, X linked, polygenic or multifactorial, chromosomal, and nontraditional inheritance; dominant genetic conditions, including neurofibromatosis I (von Recklinghausen disease), tuberous sclerosis, Marfan syndrome, Ehlers Danlos syndrome, malignant hyperthermia, primary bone dysplasias, branchio oto renal syndrome, Gorlin syndrome, Gardner syndrome, single central incisor, Treacher Collins syndrome, cleidocranial dysostosis and pyknodysostosis, craniosynostosis syndromes (Apert, Crouzon, Saethre Chotzen, Pfeiffer), velo cardio facial syndrome, and oculo dento digital syndrome; autosomal recessive conditions, including cystic fibrosis, sickle cell disease, and mucopolysaccharidoses; x linked conditions, including mental retardation and ectodermal dysplasia; polygenic conditions (multifactorial), including cleft lip and palate, and neural tube defects; chromosomal syndromes, including Down syndrome, Turner syndrome, and Klinefelter syndrome; and imprinted genes, including Prader Willi syndrome, Angelman syndrome, Beckwith Wiedemann syndrome, and Williams syndrome. The chapter stresses that the dentist who looks at a patient's face and is a careful observer can provide a valuable service to the patient by recognizing potential abnormalities and referring the child to the proper medical care provider. 31 figures. 8 references.

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Lip Lesions Source: in Laskaris, G. Pocket Atlas of Oral Diseases. New York, NY: Thieme Medical Publishers, Inc. 1998. p. 257-272.

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Contact: Available from Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001. (800) 782-3488. Fax (212) 947-1112. Website: www.thieme.com. PRICE: $22.00. ISBN: 0865776350. Summary: This chapter on lip lesions is from a desktop reference tool for otolaryngologists, dentists, dermatologists, and primary care practitioners which includes coverage of both local and systemic oral disease. The classification of the material in the book is based on the morphological presentation and the site at which the clinician first sees the lesions at examination. This chapter covers disorders that exclusively affect the lips, systemic diseases that produce characteristic lip lesions, and some other entities. Topics include cheilitis glandularis, cheilitis granulomatosa, Melkersson-Rosenthal syndrome, exfoliative cheilitis, contact cheilitis, actinic cheilitis, angular cheilitis, lip-licking dermatitis, median lip fissure, angioneurotic edema, lymphedema due to radiation, and systemic diseases such as Crohn's disease, sarcoidosis, tuberculosis, and cystic fibrosis. Each of the entities is provided with a representative color plate and a brief, concise description of the definition, etiology, clinical features, differential diagnosis, laboratory tests, and directions on treatment. ·

Respiratory Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 154-172. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Respiratory disorders are common and may significantly affect dental treatment, especially general anesthesia. Respiratory diseases are often also a contraindication to opioids, benzodiazepines and other respiratory depressants. This chapter on respiratory disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include upper respiratory tract viral infections, sinusitis, lower respiratory tract infections, pulmonary tuberculosis, Legionnaire's disease (legionellosis), lung abscess, bronchiectasis, cystic fibrosis, chronic obstructive airways diseases, asthma, bronchogenic carcinoma (lung cancer), occupational lung disease, sarcoidosis, postoperative respiratory complications (including aspiration of gastric contents), obstructive sleep apnea syndrome, and respiratory distress syndromes (RDS). For each disease, the authors discuss general aspects, diagnosis and management issues,

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dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 figure. 5 tables. 51 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to cystic fibrosis have been published that consolidate information across various sources. These too might be useful in gaining access to additional guidance on cystic fibrosis. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:26 ·

1998-1999 Complete Directory for People with Rare Disorders Source: Lakeville, CT: Grey House Publishing, Inc. 1998. 726 p. Contact: Available from Grey House Publishing, Inc. Pocket Knife Square, Lakeville, CT 06039. (860) 435-0868. Fax (860) 435-0867. PRICE: $190.00. ISBN: 0939300982. Summary: This directory, from the National Organization for Rare Disorders (NORD) provides a wealth of information on diseases and organizations. The directory offers four sections: disease descriptions, disease specific organizations, umbrella organizations, and government agencies. In the first section, the directory includes descriptions of 1,102 rare diseases in alphabetical order. Each entry defines the disorder, then refers readers to the organizations that might be of interest. Diseases related to digestive diseases include achalasia, Addison's disease, Alagille syndrome, Barrett's esophagus, Budd Chiari syndrome, Caroli disease, celiac sprue, cholangitis, cholecystitis, cirrhosis, colitis, Crohn's disease, Cushing syndrome, cystic fibrosis, diverticulitis, Dubin Johnson syndrome, fructose intolerance, galactosemia, gastritis, gastroesophageal reflux, hepatitis, Hirschprung's disease, Hurler syndrome, imperforate anus, irritable bowel syndrome, jejunal atresia, Korsakoff's syndrome, lipodystrophy, maple syrup urine disease, Morquio syndrome, polyposis, porphyria, proctitis, prune belly syndrome, sarcoidosis, Stevens Johnson

You will need to limit your search to “Directories” and cystic fibrosis 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 “cystic fibrosis” (or synonyms) into the “For these words:” box, you will only receive results on directories dealing with cystic fibrosis. You should check back periodically with this database as it is updated every three months.

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syndrome, Tropical sprue, tyrosinemia, valinemia, vitamin E deficiency, Whipple's disease, Wilson's disease, and Zollinger Ellison syndrome. Each of the 445 organizations listed in the second section is associated with a specific disease or group of diseases. In addition to contact information, there is a descriptive paragraph about the organization and its primary goals and program activities. Entries include materials published by the organization as well as the diseases the organizations cover, which refer readers to Section I. The third section lists 444 organizations that are more general in nature, serving a wide range of diseases (for example, the American Liver Foundation). The final section describes 74 agencies that are important federal government contacts that serve the diverse needs of individuals with rare disorders. A name and key word index concludes the volume. ·

9Health Fair Referral Guide Source: Denver, CO, Nine Health Services, Inc., 216 p., 1994. Contact: Nine Health Services, Inc., 825 East Speer Boulevard, Suite 200, Denver, CO 80218. (303) 698-4455. Summary: 9Health Fair Referral Guide is a publication of Nine Health Services, Inc. in Denver, Colorado, and is primarily used as a resource guide by health professionals at 9Health Fairs across Colorado. The Guide was compiled as a general reference with an emphasis on agencies that serve individuals and families on a limited income. It does, however, have resources for all income levels. Each resource listed in the Referral Guide includes an address, phone number, available services and resources, and cost. Resources are listed in each of the following categories: Crisis and emergency numbers, acquired immune deficiency syndrome (AIDS), alopecia areata, Alzheimer's disease, arthritis, blood pressure screenings, cancer, cardiovascular, cerebral palsy, chiropractic, clinics, cystic fibrosis, dental care, dermatology, diabetes, disabled resources, eating disorders, epilepsy, general consumer information and education, government agencies, hearing, home health care, hospitals in metro Denver, immunizations, intestinal diseases, kidney disease, leukemia, living wills and related issues, lupus, medical societies, mental health, migrant health program, multiple sclerosis, muscular dystrophy, nutrition, orthodontics, ostomies, Parkinson's disease, physical therapy, podiatry, post-polio, prostate and testicular cancer, rehabilitation centers, respiratory diseases, runaways and shelters, safety, senior services, sexuality and family planning, sexually transmitted diseases, sickle cell anemia, shelter, smoking withdrawal and smokeless tobacco, social services agencies, speech and language, sports medicine, stress and grief, substance abuse (including alcohol and drug), suicide prevention,

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transplant resources, transportation, victim assistance, vision, and weight control. Resources are also listed for the following Colorado regions: Central and Mountain area, Eastern, Northern, Southern, and Western. Information numbers and referral services are also listed.

General Home References In addition to references for cystic fibrosis, 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/icongroupintern a · 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

Vocabulary Builder Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abscess: A localized collection of pus caused by suppuration buried in

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tissues, organs, or confined spaces. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Angioneurotic: Denoting a neuropathy affecting the vascular system; see angioedema. [EU] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Ascites: Effusion and accumulation of serous fluid in the abdominal cavity; called also abdominal or peritoneal dropsy, hydroperitonia, and hydrops abdominis. [EU] Aspiration: The act of inhaling. [EU] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any H-isomer. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Bezoars: Concretions of swallowed hair, fruit or vegetable fibers, or similar substances found in the alimentary canal. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH]

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Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] Cholangiography: Roentgenography of the biliary ducts after administration or injection of a contrast medium, orally, intravenously or percutaneously. [EU] Cholangitis: Inflammation of a bile duct. [EU] Cholecystectomy: present. [NIH]

Surgical removal of the gallbladder and gallstones, if

Cholecystitis: Inflammation of the gallbladder, caused primarily by gallstones. Gallbladder disease occurs most often in obese women older than 40 years of age. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [EU] Constipation: Infrequent or difficult evacuation of the faeces. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Crystallization: The formation of crystals; conversion to a crystalline form. [EU]

Diverticulitis: Inflammation of a diverticulum, especially inflammation related to colonic diverticula, which may undergo perforation with abscess formation. Sometimes called left-sided or L-sides appendicitis. [EU] Duodenum: The first or proximal portion of the small intestine, extending from the pylorus to the jejunum; so called because it is about 12 fingerbreadths in length. [EU] Encephalopathy: Any degenerative disease of the brain. [EU] Encopresis: Incontinence of feces not due to organic defect or illness. [NIH] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warmblooded animals. The species are either nonpathogenic or opportunistic

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pathogens. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Exfoliation: A falling off in scales or layers. [EU] Facial: Of or pertaining to the face. [EU] Flatulence: The presence of excessive amounts of air or gases in the stomach or intestine, leading to distention of the organs. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Glossitis: Inflammation of the tongue. [EU] Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hernia: (he protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH]

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Homeostasis: A tendency to stability in the normal body states (internal environment) of the organism. It is achieved by a system of control mechanisms activated by negative feedback; e.g. a high level of carbon dioxide in extracellular fluid triggers increased pulmonary ventilation, which in turn causes a decrease in carbon dioxide concentration. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperthermia: Abnormally high body temperature, especially that induced for therapeutic purposes. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Immunosuppressant: An agent capable of suppressing immune responses. [EU]

Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH] Legionellosis: Infections with bacteria of the genus legionella. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lipodystrophy: 1. any disturbance of fat metabolism. 2. a group of conditions due to defective metabolism of fat, resulting in the absence of subcutaneous fat, which may be congenital or acquired and partial or total. Called also lipoatrophy and lipodystrophia. [EU] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is lithotripsy, laser. [NIH] Lymphedema: Edema due to obstruction of lymph vessels or disorders of the lymph nodes. [NIH] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of tumours. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH]

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Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Neutropenia: Leukopenia in which the decrease in white blood cells is chiefly in neutrophils. [EU] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Perforation: 1. the act of boring or piercing through a part. 2. a hole made through a part or substance. [EU] Plague: An acute infectious disease caused by yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Podiatry: A specialty concerned with the diagnosis and treatment of foot disorders and injuries and anatomic defects of the foot. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Postoperative: Occurring after a surgical operation. [EU] Proctitis: Inflammation of the rectum. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Proteus: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the intestines of humans and a wide variety of animals, as well as in manure, soil, and polluted waters. Its species are pathogenic, causing urinary tract infections and are also considered secondary invaders, causing septic lesions at other sites of the body. [NIH] Resection: Excision of a portion or all of an organ or other structure. [EU] Retrograde: 1. moving backward or against the usual direction of flow. 2. degenerating, deteriorating, or catabolic. [EU]

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Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] 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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Sulfites: Inorganic salts of sulfurous acid. [NIH] Syphilis: A contagious venereal disease caused by the spirochete treponema pallidum. [NIH] Tartrazine: An anionic, hydrophilic azo dye with an orange-yellow color used in fabrics, foods and cosmetics, and as a biological stain. [NIH] Testicular: Pertaining to a testis. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Toxoplasmosis: An acute or chronic, widespread disease of animals and humans caused by the obligate intracellular protozoon Toxoplasma gondii, transmitted by oocysts containing the pathogen in the feces of cats (the definitive host), usually by contaminated soil, direct exposure to infected feces, tissue cysts in infected meat, or tachyzoites (proliferating forms) in blood. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy.

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Triglycerides are obtained primarily from fat in foods. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Vibrio: A genus of vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH]

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CHAPTER 7. MULTIMEDIA ON CYSTIC FIBROSIS Overview Information on cystic fibrosis 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 cystic fibrosis. 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.

Video Recordings Most medical conditions do not have a video dedicated to them. If they do, they are often rather technical in nature. An excellent source of multimedia information on cystic fibrosis is the Combined Health Information Database. You will need to limit your search to “video recording” and “cystic fibrosis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, 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 “Videorecording (videotape, videocassette, etc.).” By making these selections and typing “cystic fibrosis” (or synonyms) into the “For these words:” box, you will only receive results on video productions. The following is a typical result when searching for video recordings on cystic fibrosis:

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·

There is a future Source: Durham, NC: Duke University Medical Center. 1990. 1 videotape (14:30 minutes). Contact: Available from Julia Gaskel, Duke University Medical Center, Box 2916, Durham, NC 27710. Telephone: (919) 684-3401. $35.00 , rental $20.00. Summary: This videotape shows interviews of eight adolescents describing their struggles and the uncertainties of living with a chronic illness. The different illnesses include cancer, sickle cell disease, asthma, Hodgkin disease, and cystic fibrosis. These young people talk frankly about their problems and address issues such as friendship, independence, and the possibility of death.

Bibliography: Multimedia on Cystic Fibrosis 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 cystic fibrosis (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 cystic fibrosis. For more information, follow the hyperlink indicated: ·

Adolescents, 1979. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: CF Foundation, c1980

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Allied professionals. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: C.F. Foundation, c1980

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Breathing. Source: a presentation of Films for the Humanities & Sciences; a Granada production for Channel Four; Year: 1995; Format: Videorecording; Princeton, NJ: Films for the Humanities & Sciences, c1995

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Children. Source: parents 1979 / a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: CF Foundation, c1980

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·

Cystic fibrosis : recorded at DDW 1990, San Antonio. Year: 1990; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, c1990

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Cystic fibrosis. Source: [presented by] the University of Texas Medical School at Houston; produced by UT-TV, Houston; Year: 1991; Format: Videorecording; [Houston, Tex.]: UT-TV, Houston, c1991

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Cystic fibrosis. Source: Harry Shwachman; Year: 1976; Format: Slide; New York: Medcom, c1976

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Cystic fibrosis. Source: Trainex Corporation; Year: 1976; Format: Filmstrip; Garden Grove, Calif.: Trainex, c1976

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Diagnosing & treating cystic fibrosis. Source: a presentation of Films for the Humanities & Sciences; a Leeds University Television production for Shotlist; Year: 1999; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1999

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Diagnosis and management of cystic fibrosis. Source: National Institute of Arthritis and Metabolic Diseases and National Cystic Fibrosis Research Foundation; [made by] Sturgis-Grant Productions, inc; Year: 1967; Format: Motion picture; New York: The Foundation; [Atlanta: for loan by National Medical Audiovisual Center], 1967

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Diagnosis of cystic fibrosis in adults. Source: presented by the American Thoracic Society, American Lung Association, ALA/ATS Component Committee on Learning Resources; Year: 1981; Format: Slide; [New York, N.Y.]: The Committee, 1981

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Early diagnosis of cystic fibrosis. Source: American Lung Association, American Thoracic Society; produced by Emerson-Braxton & Co; Year: 1985; Format: Slide; [New York, N.Y.]: American Lung Association, c1985

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Highlights : selected proceedings from the Thirteenth Annual North American Cystic Fibrosis Conference, Seattle, Washington, October 710, 1999. Source: Cystic Fibrosis Foundation; produced by Med Doc Medical Communications; Year: 1999; Format: Electronic resource; Bloomsbury, NJ: Med Doc Medical Communications, [1999?]

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Living with cystic fibrosis . Year: 1997; Format: Videorecording; Browns Mills, NJ: Deborah Heart & Lung Center; Sherborn, MA: Distributed by Aquarius Productions, c1997

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Living with cystic fibrosis. Source: [produced by] Amram Nowak Associates for the National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Public Health Service, the Department of Health and Human Servi; Year: 1980; Format: Motion picture; Rockville, Md.: The Foundation, c1980

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·

Married couples. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: CF Foundation, c1980

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New concepts in managing malabsorption in cystic fibrosis. Source: developed and produced for Temple University School of Medicine by Gardiner-Caldwell SynerMed; Year: 1991; Format: Videorecording; [Califon, N.J.]: Gardiner-Caldwell SynerMed, c1991

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Newly diagnosed family. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: CF Foundation, c1980

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PKU and cystic fibrosis : sterilization and artificial insemination. Source: co-authored by Garrett E. Bergman, John H. Sorenson; produced by the Medical College of Pennsylvania, Office of Medical Education, Audiovisual Section; Year: 1978; Format: Slide; [Philadelphia]: The Section, c1978

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Pulmonary disorders in school-aged children. Source: [presented by] the Cleveland Clinic Foundation; Year: 1993; Format: Videorecording; [Cleveland, Ohio]: Cleveland Clinic Foundation, c1993

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Recently bereaved parents. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1982; Format: Videorecording; [Bethesda, Md.]: C.F. Foundation, c1982

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Siblings. Source: a production of the Office of Learning ResourcesTelevision, School of Medicine, University of California, San Diego; Year: 1983; Format: Videorecording; [Bethesda, Md.]: C.F. Foundation, c1983

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Staff burnout. Source: a production of the Office of Learning ResourcesTelevision, School of Medicine, University of California, San Diego; Year: 1984; Format: Videorecording; [Bethesda, Md.]: C.F. Foundation, c1984

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Story of Susan McKellar. Source: [produced by] CBC Television; Year: 1981; Format: Videorecording; [Ottawa, Ont.]: Canadian Broadcasting Corp., c1981

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Sweat testing for cystic fibrosis of the pancreas. Source: author, George K. Summer; Year: 1981; Format: Videorecording; Chapel Hill, NC: Health Sciences Consortium, 1981

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Three generation family. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: CF Foundation, c1980

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·

Young adults 1978. Source: a production of the Office of Learning Resources-Television, School of Medicine, University of California, San Diego; Year: 1980; Format: Videorecording; [Bethesda, Md.]: CF Foundation, c1980

Vocabulary Builder Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Dehydration: The condition that results from excessive loss of body water. Called also anhydration, deaquation and hypohydration. [EU] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Sterilization: 1. the complete destruction or elimination of all living microorganisms, accomplished by physical methods (dry or moist heat), chemical agents (ethylene oxide, formaldehyde, alcohol), radiation (ultraviolet, cathode), or mechanical methods (filtration). 2. any procedure by which an individual is made incapable of reproduction, as by castration, vasectomy, or salpingectomy. [EU]

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CHAPTER 8. PERIODICALS AND NEWS ON CYSTIC FIBROSIS Overview Keeping up on the news relating to cystic fibrosis can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on cystic fibrosis. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover cystic fibrosis beyond and including those which are published by parent 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 cystic fibrosis 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 “cystic fibrosis” 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. The following is typical of press releases that can be found on PR Newswire: ·

Targeted Genetics Completes Enrollment in Phase II Cystic Fibrosis Gene Therapy Clinical Trial Summary: SEATTLE, May 16 /PRNewswire-FirstCall/ -- Targeted Genetics Corporation (Nasdaq: TGEN) today announced that it has enrolled the last patient in its Phase II cystic fibrosis (CF) clinical trial. The patient has received the first of three doses of placebo or study agent, tgAAVCF, the Company's product candidate for the treatment of CF. This 36-patient clinical trial is designed to evaluate the safety and clinical impact of tgAAVCF in patients with CF. Targeted Genetics intends to announce the results of this Phase II study at the North American Cystic Fibrosis meeting in October 2002. "We are excited to reach this milestone in the first study ever to evaluate repeat dosing of an AAV-based product in patients with CF," said Barrie J. Carter, Ph.D., Executive Vice President and Chief Scientific Officer of Targeted Genetics Corporation. "Targeted Genetics has led the clinical development of AAV-based products, being the first to bring AAV vectors into clinical development, the first to conduct Phase II trials and the first to assess repeat dosing of AAV vectors. Upon completion of this study, we will have a solid body of data relating to the safety and ability of tgAAVCF to address the genetic defect that causes CF. Also upon completion of this study we will have the first data to assess the impact of tgAAVCF on secondary clinical endpoints such as lung function and inflammation." Targeted Genetics has now treated more than 90 patients with tgAAVCF over the course of its clinical program to date. An independent Data Safety Monitoring Committee (DSMC), established by the Cystic Fibrosis Foundation (CFF) to monitor safety in the Phase II trial, has provided ongoing reviews during the trial and allowed the Company to lower the age of patient enrollment. As a result, Targeted Genetics may include patients as young as 12 years of age. The study was performed through

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the CFF's Therapeutic Development Network, a Phase I/II clinical trial network. After the first safety committee review in July 2001, the DSMC determined that the safety profile of repeat dosing of tgAAVCF warranted lowering the age limit for participation in this Phase II study from 18 to 15 years of age. Following a subsequent review in November 2001, the DSMC determined that the age limit could be lowered from 15 to 12. Sixteen of the 36 patients participating in this study are under the age of 18. "CF is a progressive disease," continued Dr. Carter. "With tgAAVCF treatment, we hope to halt or significantly slow the development of the irreversible lung damage that leads to lung failure, the primary cause of mortality in CF patients. We believe that tgAAVCF may have the most impact on younger patients who have not yet experienced significant damage to their lungs." Targeted Genetics is collaborating with Celltech Group plc on the development and commercialization of tgAAVCF, a product candidate that uses an AAV vector to deliver a copy of the CFTR gene to the airways of patients with CF. Loss of proper function of the CFTR gene is the cause of CF. While current therapies treat the symptoms of CF, tgAAVCF has the potential to address the underlying cause of the disease. Data from a Phase I, single dose, dose escalation study of aerosolized tgAAVCF in patients with CF were presented in June of 2000. This study demonstrated that aerosolized tgAAVCF was well tolerated and had a good safety profile. Dose-dependent gene transfer was observed and the aerosol formulation was shown to deliver tgAAVCF to multiple regions of the lung. The current Phase II, double-blind, randomized, placebo-controlled study evaluates the safety and tolerability of repeat dosing of tgAAVCF and will assess the impact of tgAAVCF on lung function, inflammation and microbiology of CF patients ages 12 and older with mild lung disease. Immune response to the product will be evaluated. Targeted Genetics is also evaluating gene transfer and gene expression as secondary endpoints in some patients, which will provide further understanding of the product candidate. A total of 36 patients are being evaluated, 18 in the treatment group and 18 in the placebo group. Patients in the treatment group will receive 1013 DNAse resistant, or vector, particles

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(DRP) of tgAAVCF delivered via nebulizer once a month for three months and will then be followed for 90 days.

CYSTIC FIBROSIS BACKGROUND Cystic fibrosis results from the loss of function of the CFTR gene. Normally, the protein encoded by this gene is found in the respiratory passageways, pancreas, salivary and sweat glands, where it helps to regulate the cellular concentration of chloride ions and water. In CF patients, the loss of this gene product's function leads to the production and build-up in the lungs and sinuses of thick sticky mucus, colonization by bacteria and the invasion of white blood cells, thus causing inflammation. These events produce scarring in the lung, which ultimately results in loss of respiratory function. Common symptoms include very salty-tasting skin, persistent coughing, wheezing or pneumonia, excessive appetite but poor weight gain, and bulky stools. It is estimated that 60,000 people worldwide have cystic fibrosis, including approximately 30,000 people in the United States. The median age of survival for patients with CF is approximately 32 years. For more information about CF and Cystic Fibrosis Foundation please visit http://www.cff.org. Targeted Genetics Corporation develops gene therapy products for the treatment of acquired and inherited diseases. The Company has lead clinical product development programs targeting cystic fibrosis and cancer, and a promising pipeline of product candidates focused on hemophilia, arthritis, cancer, lysosomal storage diseases and AIDS prophylaxis. The Company has a broad platform of gene delivery technologies and, through its majority-owned subsidiary, CellExSys, a promising body of technology for cellular therapy. For more information about Targeted Genetics Corporation please visit the Company's web site at http://www.targetedgenetics.com . NOTE: This release contains forward-looking statements regarding the development of our product candidates, which are based on the opinions and estimates of our management at the time the statements are made and are subject to risks and uncertainties that could cause actual results to differ materially from those expected or implied by the forwardlooking statements.

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Inaccurate assumptions and known and unknown risks and uncertainties can affect the accuracy of these forward-looking statements. Factors that could affect our actual results include, but are not limited to, the timing and nature of the results of our clinical trials, as well as the other risk factors described in the section entitled "Factors Affecting Our Operating results, Our Business and Our Stock Price" included in our Annual Report on Form 10-K for the year ended December 31, 2001 filed with the Securities and Exchange Commission. You should not rely unduly on these forward-looking statements, which apply only as of the date of this release. We undertake no obligation to update any forward-looking statement to reflect new information, circumstances or events after the date of this release or to reflect the occurrence of unanticipated events.

Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to cystic fibrosis. 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 “cystic fibrosis” (or synonyms). The following was recently listed in this archive for cystic fibrosis: ·

Summer camp beneficial for cystic fibrosis patients Source: Reuters Health eLine Date: mai 02, 2002 http://www.reuters.gov/archive/2002/05/02/eline/links/20020502elin 015.html

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P. aeruginosa adaptation to cystic fibrosis airways triggers inflammatory response Source: Reuters Medical News Date: mars 26, 2002 http://www.reuters.gov/archive/2002/03/26/professional/links/20020 326scie005.html

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Blocking bug adaptation might help cystic fibrosis Source: Reuters Health eLine Date: mars 25, 2002 http://www.reuters.gov/archive/2002/03/25/eline/links/20020325elin 003.html

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·

Iron deficiency linked with cystic fibrosis disease severity Source: Reuters Medical News Date: février 04, 2002 http://www.reuters.gov/archive/2002/02/04/professional/links/20020 204clin019.html

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Chronic sinusitis linked to cystic fibrosis gene Source: Reuters Health eLine Date: janvier 07, 2002 http://www.reuters.gov/archive/2002/01/07/eline/links/20020107elin 002.html

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Repairing defect with pre-mRNA partially corrects cystic fibrosis pathology Source: Reuters Industry Breifing Date: décembre 21, 2001 http://www.reuters.gov/archive/2001/12/21/business/links/20011221 scie005.html

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Transplant doesn't help most with cystic fibrosis Source: Reuters Health eLine Date: décembre 04, 2001 http://www.reuters.gov/archive/2001/12/04/eline/links/20011204elin 008.html

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Altering lung acidity may help in cystic fibrosis Source: Reuters Health eLine Date: novembre 19, 2001 http://www.reuters.gov/archive/2001/11/19/eline/links/20011119elin 015.html

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New weapons identified against lung inflammation in cystic fibrosis Source: Reuters Medical News Date: octobre 30, 2001 http://www.reuters.gov/archive/2001/10/30/professional/links/20011 030scie001.html

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Tranzyme, Cystic Fibrosis Foundation affiliate to develop cell lines for CF therapy Source: Reuters Industry Breifing Date: octobre 09, 2001 http://www.reuters.gov/archive/2001/10/09/business/links/20011009 inds008.html

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Inhaled tobramycin can clear P. aeruginosa from airways of cystic fibrosis patients Source: Reuters Industry Breifing Date: septembre 24, 2001 http://www.reuters.gov/archive/2001/09/24/business/links/20010924 clin014.html

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New line of cystic fibrosis drugs looks promising Source: Reuters Medical News Date: août 28, 2001 http://www.reuters.gov/archive/2001/08/28/professional/links/20010 828drgd005.html

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Development-stage cystic fibrosis drugs look promising Source: Reuters Industry Breifing Date: août 28, 2001 http://www.reuters.gov/archive/2001/08/28/business/links/20010828 drgd004.html

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Australia has best cystic fibrosis screening Source: Reuters Health eLine Date: août 27, 2001 http://www.reuters.gov/archive/2001/08/27/eline/links/20010827elin 019.html

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Australia claims to have best cystic fibrosis screening Source: Reuters Medical News Date: août 27, 2001 http://www.reuters.gov/archive/2001/08/27/professional/links/20010 827publ001.html

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Demegen gets $1.5 million grant to develop inhalable Cystic Fibrosis treatment Source: Reuters Industry Breifing Date: août 22, 2001 http://www.reuters.gov/archive/2001/08/22/business/links/20010822 inds010.html

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Cystic fibrosis patients are susceptible to pseudomonas cross-infection Source: Reuters Medical News Date: août 16, 2001 http://www.reuters.gov/archive/2001/08/16/professional/links/20010 816clin017.html

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·

Study: Poorer cystic fibrosis patients fare worse Source: Reuters Health eLine Date: juin 14, 2001 http://www.reuters.gov/archive/2001/06/14/eline/links/20010614elin 010.html

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Gene therapy for cystic fibrosis faces many hurdles Source: Reuters Medical News Date: juin 08, 2001 http://www.reuters.gov/archive/2001/06/08/professional/links/20010 608clin007.html

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Cystic fibrosis gene therapy faces many hurdles Source: Reuters Health eLine Date: juin 04, 2001 http://www.reuters.gov/archive/2001/06/04/eline/links/20010604elin 026.html

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SciClone cystic fibrosis drug is granted orphan drug status in Europe Source: Reuters Industry Breifing Date: mai 22, 2001 http://www.reuters.gov/archive/2001/05/22/business/links/20010522 rglt003.html

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InterMune to co-develop MoliChem investigational cystic fibrosis drug Source: Reuters Industry Breifing Date: mai 11, 2001 http://www.reuters.gov/archive/2001/05/11/business/links/20010511 inds005.html

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UK split on merits of cystic fibrosis screening Source: Reuters Medical News Date: mai 03, 2001 http://www.reuters.gov/archive/2001/05/03/professional/links/20010 503publ002.html

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Cystic fibrosis patients have positive outlook Source: Reuters Health eLine Date: mai 02, 2001 http://www.reuters.gov/archive/2001/05/02/eline/links/20010502elin 009.html

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UK to screen all newborns for cystic fibrosis Source: Reuters Health eLine Date: avril 30, 2001 http://www.reuters.gov/archive/2001/04/30/eline/links/20010430elin 024.html

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Height helps measure survival in cystic fibrosis Source: Reuters Health eLine Date: avril 13, 2001 http://www.reuters.gov/archive/2001/04/13/eline/links/20010413elin 004.html

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Intravenous pamidronate increases BMD in adults with cystic fibrosis Source: Reuters Industry Breifing Date: mars 26, 2001 http://www.reuters.gov/archive/2001/03/26/business/links/20010326 clin002.html

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New vectors may advance cystic fibrosis gene therapy Source: Reuters Medical News Date: mars 06, 2001 http://www.reuters.gov/archive/2001/03/06/professional/links/20010 306drgd001.html

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Profile Therapeutics and Forum develop inhaled antibiotic for cystic fibrosis Source: Reuters Industry Breifing Date: mars 01, 2001 http://www.reuters.gov/archive/2001/03/01/business/links/20010301 inds011.html

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InterMune begins phase II trial of Actimmune for cystic fibrosis Source: Reuters Industry Breifing Date: février 28, 2001 http://www.reuters.gov/archive/2001/02/28/business/links/20010228 drgd003.html

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Discovery could improve cystic fibrosis treatment Source: Reuters Health eLine Date: février 28, 2001 http://www.reuters.gov/archive/2001/02/28/eline/links/20010228elin 013.html

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Dyax cystic fibrosis candidate enters phase IIa trial Source: Reuters Industry Breifing Date: février 13, 2001 http://www.reuters.gov/archive/2001/02/13/business/links/20010213 drgd006.html

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·

Internet group helps cystic fibrosis patients Source: Reuters Health eLine Date: février 07, 2001 http://www.reuters.gov/archive/2001/02/07/eline/links/20010207elin 001.html

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Neonatal screening prevents growth stunting in cystic fibrosis patients Source: Reuters Medical News Date: janvier 09, 2001 http://www.reuters.gov/archive/2001/01/09/professional/links/20010 109publ002.html

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Positive pressure enhances optimal aerosol deposition in cystic fibrosis Source: Reuters Medical News Date: janvier 08, 2001 http://www.reuters.gov/archive/2001/01/08/professional/links/20010 108clin006.html

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Early cystic fibrosis screening can improve health Source: Reuters Health eLine Date: janvier 08, 2001 http://www.reuters.gov/archive/2001/01/08/eline/links/20010108elin 008.html

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Sensor technology updates sweat test for cystic fibrosis Source: Reuters Industry Breifing Date: décembre 22, 2000 http://www.reuters.gov/archive/2000/12/22/business/links/20001222 drgd002.html

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Sensors replace lab techs in new cystic fibrosis test Source: Reuters Health eLine Date: décembre 06, 2000 http://www.reuters.gov/archive/2000/12/06/eline/links/20001206elin 007.html

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Pathogens common in nebulizers used by cystic fibrosis patients Source: Reuters Medical News Date: novembre 24, 2000 http://www.reuters.gov/archive/2000/11/24/professional/links/20001 124epid001.html

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Targeted Genetics begins phase II cystic fibrosis drug study Source: Reuters Industry Breifing Date: novembre 17, 2000 http://www.reuters.gov/archive/2000/11/17/business/links/20001117 drgd004.html

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Fine mist could enhance gene therapy for cystic fibrosis Source: Reuters Health eLine Date: octobre 23, 2000 http://www.reuters.gov/archive/2000/10/23/eline/links/20001023elin 016.html

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Genentech recalls one lot of cystic fibrosis treatment Pulmozyme Source: Reuters Industry Breifing Date: octobre 12, 2000 http://www.reuters.gov/archive/2000/10/12/business/links/20001012 rglt002.html

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Bacteria form shield against drugs in cystic fibrosis Source: Reuters Health eLine Date: octobre 11, 2000 http://www.reuters.gov/archive/2000/10/11/eline/links/20001011elin 007.html

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Chronic sinus infections linked to cystic fibrosis gene Source: Reuters Health eLine Date: octobre 10, 2000 http://www.reuters.gov/archive/2000/10/10/eline/links/20001010elin 012.html

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Inspire files IND for potential cystic fibrosis treatment Source: Reuters Industry Breifing Date: octobre 03, 2000 http://www.reuters.gov/archive/2000/10/03/business/links/20001003 rglt007.html

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Hyperoxaluria, hypocalciuria common in children with cystic fibrosis Source: Reuters Medical News Date: septembre 22, 2000 http://www.reuters.gov/archive/2000/09/22/professional/links/20000 922clin009.html

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Affymetrix to develop GeneChip array for cystic fibrosis studies Source: Reuters Industry Breifing Date: septembre 05, 2000 http://www.reuters.gov/archive/2000/09/05/business/links/20000905 inds001.html

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Newborn cystic fibrosis screening provides double payoff Source: Reuters Health eLine Date: septembre 01, 2000 http://www.reuters.gov/archive/2000/09/01/eline/links/20000901elin 015.html

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·

Neonatal cystic fibrosis screening valuable Source: Reuters Medical News Date: septembre 01, 2000 http://www.reuters.gov/archive/2000/09/01/professional/links/20000 901clin004.html

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Fertility counseling inadequate for UK cystic fibrosis patients Source: Reuters Medical News Date: août 31, 2000 http://www.reuters.gov/archive/2000/08/31/professional/links/20000 831clin022.html 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 MEDLINEplus 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. The following was recently indexed as relating to cystic fibrosis:

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 “cystic fibrosis” (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:

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http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “cystic fibrosis” (or synonyms). If you know the name of a company that is relevant to cystic fibrosis, 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.

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 “cystic fibrosis” (or synonyms).

Newsletters on Cystic Fibrosis Given their focus on current and relevant developments, newsletters are often more useful to parents than academic articles. You can find newsletters using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Your investigation must limit the search to “Newsletter” and “cystic fibrosis.” 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.” By making these selections and typing in “cystic fibrosis” or synonyms into the “For these words:” box, you will only receive results on newsletters. The following list was generated using the options described above: ·

Commitment Source: Bethesda, MD: Cystic Fibrosis Foundation (CFF). 1994. [12 p. average]. Contact: Available from Cystic Fibrosis Foundation (CFF). 6931 Arlington Road, Bethesda, MD 20814. (800) 344-4823 or (301) 951- 4422; FAX (301) 951-6378. PRICE: Free. Summary: This newsletter, published by the Cystic Fibrosis Foundation (CFF), presents information about cystic fibrosis and the CFF. A typical issue includes articles about medical and social aspects of cystic fibrosis, gene therapy research and clinical trials, CFF news and announcements, research updates, conference highlights, chapter activities and fundraising events, and publication reviews.

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Academic Periodicals covering Cystic Fibrosis Academic periodicals can be a highly technical yet valuable source of information on cystic fibrosis. We have compiled the following list of periodicals known to publish articles relating to cystic fibrosis 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 cystic fibrosis 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, visit the Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/ you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.” The following is a sample of periodicals which publish articles on cystic fibrosis: ·

Acta Paediatrica (Oslo, Norway : 1992). (Acta Paediatr) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ac ta+Paediatrica+(Oslo,+Norway+:+1992)&dispmax=20&dispstart=0

·

Archives of Disease in Childhood. (Arch Dis Child) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ar chives+of+Disease+in+Childhood&dispmax=20&dispstart=0

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British Medical Journal. (Br Med J) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Bri tish+Medical+Journal&dispmax=20&dispstart=0

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Cell Biology International. (Cell Biol Int) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ce ll+Biology+International&dispmax=20&dispstart=0

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Clinical Chemistry. (Clin Chem) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Chemistry&dispmax=20&dispstart=0

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·

Medical and Pediatric Oncology. (Med Pediatr Oncol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=M edical+and+Pediatric+Oncology&dispmax=20&dispstart=0

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Pediatric Nursing. (Pediatr Nurs) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Pe diatric+Nursing&dispmax=20&dispstart=0

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Pediatric Pulmonology. (Pediatr Pulmonol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Pe diatric+Pulmonology&dispmax=20&dispstart=0

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Physical Therapy. (Phys Ther) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ph ysical+Therapy&dispmax=20&dispstart=0

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CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help children with cystic fibrosis. 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 medical conditions, 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

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

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

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National 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

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

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

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

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

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

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

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

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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

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

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

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

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

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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

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

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

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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

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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

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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

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

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

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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

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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

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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

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

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

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

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

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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

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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

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

·

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

·

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

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

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

·

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 cystic fibrosis, 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 cystic fibrosis 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 “cystic fibrosis” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with cystic fibrosis. The following is a sample result: ·

Demonstrating cost-effectiveness of nutrition services for children with special health care needs: A national network Source: Arlington, VA: National Center for Education in Maternal and Child Health; Los Angeles, CA: Center for Child Development and Developmental Disabilities, University of Southern California. 1999. 67 pp. Contact: Available from National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA 22182-

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2536. Telephone: (703) 356-1964 or (888) 434-4MCH / fax: (703) 821-2098 / e-mail: [email protected]. Available at no charge. Summary: This report summarizes a literature review and a field survey related to the cost-effectiveness of nutrition services for children with special health care needs (CSHCN). The literature review concentrates on cystic fibrosis, cerebral palsy, and failure to thrive. It includes an overview of each illness and the outcome indicators cited in the literature. The survey analysis results are presented by agency setting (i.e., clinical, public health, or university setting) and by federal region. A report on the expert panel convened to identify nutrition indicators for CSHCN, a description of workshop participant projects, and a list of workshop participants are included. The report was prepared for the Maternal and Child Health Interorganizational Nutrition Group (MCHING). [Funded by the Maternal and Child Health Bureau]. ·

Genetic tests and health insurance: Results of a survey Source: Washington, DC: Office of Technology Assessment, U.S. Congress. 1992. Contact: Available from Superintendent of Documents, U.S. Government Printing Office, P.O. Box 371954, Pittsburgh, PA 15250-7954. Telephone: (202) 512-1991 for public information (D.C. office) or (202) 512-1800 for ordering and publication information (D.C. office) / fax: (202) 512-1293 (public information); (202) 512-2250 (ordering) / Web site: http://www.access.gpo.gov. $5.00; stock number 052-003-01310-0. Summary: This report provides information about a survey of commercial insurers, Blue Cross and Blue Shield plans, and health maintenance organizations that offer individual or medically underwritten group policies. The survey was designed to identify health insurers' attitudes toward reimbursement for genetic tests and policies for using test results in underwriting. Specific topics include a respondent profile, treatment of applications, underwriting practices, factors in insurability, reimbursement, coverage for cystic fibrosis carrier tests, economic analysis, impact of genetic tests on business practices, attitudes toward genetic information, and use of genetic tests.

·

Introduction to cystic fibrosis for patients and families Source: Bethesda, MD: Cystic Fibrosis Foundation. 1991. 95 pp. Contact: Available from Cystic Fibrosis Foundation, 6931 Arlington Road, Suite 200, Bethesda, MD 20814. Telephone: (301) 951-4422 or (800) 344- 4823 / fax: (301) 951-6378 / e-mail: [email protected] / Web site: http://www.cff.org. Available at no charge.

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Summary: This book is written to help families of children with cystic fibrosis learn about the disease and identify sources of information and support. Chapters discuss what is cystic fibrosis and how it is diagnosed, how it affects the sweat glands, respiratory system, gastrointestinal system, and the reproductive system, and how to live with cystic fibrosis. ·

The impact of health maintenance organizations on accessibility, satisfaction and cost of health care for children with special needs Source: Madison, WI: Center for Health Systems Research and Analysis. 1990. 119 pp. Contact: Available from Center for Public Representation, P.O. Box 260049, Madison, WI 53726-0049. Telephone: (608) 251-4008 / fax: (608) 251- 1263 / e-mail: [email protected]. / Web site: http://www.law.wisc.edu. $20.00. Summary: This report describes a study of five health maintenance organizations in Dane and Milwaukee Counties, Wisconsin. The report examined what the plans did and did not cover, costs to families and family satisfaction, for the following three diagnoses: acute lymphocytic leukemia, cystic fibrosis, and developmental delay. Implications and recommendations are also reported.

·

About Lungs and Lung Diseases 1994 edition Source: 1980. Contact: Channing L. Bete Company, Incorporated, 200 State Rd., South Deerfield, MA 01373-0200. (800) 628-7733. Summary: This brochure discusses lung diseases, how they can be avoided, and how to care for the lungs. The brochure explains the function of the lungs and how they work. It identifies the body's natural defenses against lung infections and those factors that weaken these defenses. The brochure examines a number of lung infections and diseases such as influenza, pneumonia, tuberculosis (TB), asthma, chronic bronchitisemphysema, lung cancer, cystic fibrosis, and pneumoconiosis. For each disease, the brochure explains the causes, who is affected by them, symptoms, treatment, complications that may occur, and how they can be prevented. It advises the reader against smoking, and for those who are smokers, it recommends quitting as soon as possible. The brochure suggests that the reader avoid inhaling pollutants and other dangerous chemicals. The brochure recommends a healthy diet, exercise, rest, and regular check-ups for lung maintenance. It summarizes the future of lung diseases.

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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, parents and the public.32 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “cystic fibrosis” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Items Found Journal Articles 21378 Books / Periodicals / Audio Visual 348 Consumer Health 84 Meeting Abstracts 32 Other Collections 9 Total 21851

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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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 “cystic fibrosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists36 Some parents 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 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. 36 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 37 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. 33 34

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articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. 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, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

·

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 the following Web site: http://www.lexical.com/Metaphrase.html.

The Genome Project and Cystic Fibrosis With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and parents want to know about how human genes relate to cystic fibrosis. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

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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 “cystic fibrosis” (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 cystic fibrosis: ·

Cystic Fibrosis Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?219700

·

Cystic Fibrosis Modifier 1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?603855

·

Cystic Fibrosis Transmembrane Conductance Regulator Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?602421

·

Cystic Fibrosis with Helicobacter Pylori Gastritis, Megaloblastic Anemia, and Subnormal Mentality Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?219721

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.

39

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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. This Web site categorizes each disorder by the system of the body associated with it. 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: ·

Cancer: Uncontrolled cell division. Examples: Breast And Ovarian Cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

·

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

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·

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 “cystic fibrosis” (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 “cystic fibrosis” (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 cystic fibrosis (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Atlas of Pediatric Physical Diagnosis by Basil J. Zitelli, Holly W. Davis (Editor); Hardcover, 3rd edition (March 1997), Mosby-Year Book; ISBN: 0815199309; http://www.amazon.com/exec/obidos/ASIN/0815199309/icongroupinterna · 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 · The 5-Minute Pediatric Consult by M. William Schwartz (Editor); Hardcover - 1050 pages, 2nd edition (January 15, 2000), Lippincott, Williams & Wilkins; ISBN: 0683307444; http://www.amazon.com/exec/obidos/ASIN/0683307444/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

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· 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 · Nelson Textbook of Pediatrics by Richard E. Behrman (Editor), et al; Hardcover - 2414 pages, 16th edition (January 15, 2000), W B Saunders Co; ISBN: 0721677673; http://www.amazon.com/exec/obidos/ASIN/0721677673/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 · 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 Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Lymphocytic: Pertaining to, characterized by, or of the nature of lymphocytes. [EU] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH]

221

PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics relating to cystic fibrosis and related conditions.

Researching Your Child’s Medications 223

APPENDIX A. RESEARCHING YOUR CHILD’S MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to treat cystic fibrosis. While a number of hard copy or CD-Rom resources are available to parents 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 child’s medications. You may also want to research medications that your child is currently taking for other conditions as they may interact with medications for cystic fibrosis. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of cystic fibrosis. 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 Child’s Medications: The Basics42 The Agency for Health Care Research and Quality has published extremely useful guidelines on the medication aspects of cystic fibrosis. Giving your child medication can involve many steps and decisions each day. The AHCRQ recommends that parents take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions, your child may be spared from possible problems. Here are some points to cover each time a new medicine is prescribed: ·

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

·

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

·

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

Do not hesitate to tell the doctor about preferences you have for your child’s medicines. You may want your child to have a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost. Or, you may want the medicine the doctor believes will work the best. Sharing your concerns will help the doctor select the best treatment for your child. Do not be afraid to “bother” the doctor with your questions about medications for cystic fibrosis. You can also talk to a nurse or a pharmacist. They can help you better understand your child’s treatment plan. Talking over your child’s options with someone you trust can help you make better choices. Specifically, ask the doctor the following: ·

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

·

How and when to give your child the medicine, how much, and for how long.

·

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

·

What side effects your child may experience, and what to do if they occur.

·

If there are any refills, and how often.

·

About any terms or directions you do not understand.

·

What to do if your child misses a dose.

42

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

Researching Your Child’s Medications 225

·

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

Do not forget to tell the doctor about all the medicines your child is currently taking (not just those for cystic fibrosis). This includes prescription medicines and the medicines that you buy over the counter. When talking to the doctor, you may wish to prepare a list of medicines your child is currently taking including why and in what forms. 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)

Learning More about Your Child’s Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications the doctor has recommended for cystic fibrosis. 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

226 Cystic Fibrosis

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 your child is taking. Therefore, we have compiled a list of medications associated with the treatment of cystic fibrosis. 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 cystic fibrosis:

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 child’s doctor’s office.

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

43

Researching Your Child’s Medications 227

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 cystic fibrosis (including those with contraindications):44 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 information on prescribing and drug interactions. Information can be obtained at 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/.

Researching Orphan Drugs Orphan drugs are a special class of pharmaceuticals given to patients who are unaffected by existing treatments or with illnesses for which no known drug is effective. Orphan drugs are most commonly prescribed or developed

44

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

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for “rare” medical conditions.45 According to the FDA, an orphan drug (or biological) may already be approved, or it may still be experimental. A drug becomes an “orphan” when it receives orphan designation from the Office of Orphan Products Development at the FDA.46 Orphan designation qualifies the sponsor to receive certain benefits from the U.S. Government in exchange for developing the drug. The drug must then undergo the new drug approval process as any other drug would. To date, over 1000 orphan products have been designated, and over 200 have been approved for marketing. Historically, the approval time for orphan products as a group has been considerably shorter than the approval time for other drugs. This is due to the fact that many orphan products receive expedited review because they are developed for serious or life-threatening medical conditions. The cost of orphan products is determined by the sponsor of the drug and can vary greatly. Reimbursement rates for drug expenses are set by each insurance company and outlined in your child’s policy. Insurance companies will generally reimburse for orphan products that have been approved for marketing, but may not reimburse for products that are considered experimental. Consult the insurance company about specific reimbursement policies. If an orphan product has been approved for marketing, it will be available through the normal pharmaceutical supply channels. If the product has not been approved, the sponsor may make the product available on a compassionate-use basis.47 Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to cystic fibrosis using the database managed by the National Organization for Rare Disorders, Inc. (NORD), located at www.raredisease.org. Simply go to their general search page and select “Orphan Drug Database.” On this page (http://www.rarediseases.org/cgi-bin/nord/searchpage) under “Enter a search term,” type “cystic fibrosis” or a synonym into the search box. Under The U.S. Food and Drug Administration defines a rare disease or condition as “any disease or condition which affects less than 200,000 persons in the United States, or affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug.” Adapted from the U.S. Food and Drug Administration: http://www.fda.gov/opacom/laws/orphandg.htm. 46 The following is adapted from the U.S. Food and Drug Administration: http://www.fda.gov/orphan/faq/index.htm. 47 For contact information on sponsors of orphan products, contact the Office of Orphan Products Development (http://www.fda.gov/orphan/). General inquiries may be routed to the main office: Office of Orphan Products Development (HF-35); Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857; Voice: (301) 827-3666 or (800) 3007469; FAX: (301) 443-4915. 45

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“Select a database,” check the box for “NORD Orphan Drug Designation Database.” When you see a list of drugs, understand that not all of the drugs may be relevant. Some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box on the Web page: http://www.nlm.nih.gov/medlineplus/druginformation.html. Read about each drug in detail and consult with the doctor to find out if your child might benefit from these medications. You or the physician may need to contact the sponsor or NORD. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you or the physician should consult the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for cystic fibrosis or related conditions:

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for children with cystic fibrosis--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 cystic fibrosis or potentially create deleterious side effects in patients with cystic fibrosis. You should ask the physician about any contraindications, especially as these might apply to other medications that your child 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 your child to experience an unexpected side effect. Drug interactions may make medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to your child. Be sure to read the label every time you give your child a nonprescription or prescription drug, and take the time to learn about drug interactions. These

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precautions may be critical to your child’s 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 avaiable. This is why it’s especially important to read the label every time you give your child a medication. When the doctor prescribes a new drug, discuss all overthe-counter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals your child takes. Ask your pharmacist for the package insert for each drug prescribed. 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 cystic fibrosis. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt your child. 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 cystic fibrosis. The FDA warns to watch out for48: ·

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)

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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.

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

48

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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

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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

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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

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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 child’s doctor or your friends 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 cystic fibrosis. Finally, at the conclusion of this chapter, we will provide a list of readings on cystic fibrosis from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.

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What Is CAM?49 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 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?50 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 49 50

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

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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 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 illness, 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.

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Naturopathic medicine is based on the theory that a medical condition is the manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than treatment for the condition itself. 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.

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 medical conditions 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 conditions.

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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. 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 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.

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Can Alternatives Affect My Child’s Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your child’s medical treatment. It becomes all the more important to speak with the 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 everyone.51 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 child’s healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires that the practitioner know of all conventional and alternative therapies that your child is taking. 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 Cystic Fibrosis Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for cystic fibrosis. 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. The Combined Health Information Database For a targeted search, The Combined Health Information Database is a bibliographic database produced by health-related agencies of the Federal Government (mostly from the National Institutes of Health). This database is 51

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

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updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “cystic fibrosis” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: ·

Therapeutic Applications of Taurine Source: Alternative Medicine Review. 3(2): 128-136. April 1998. Summary: This journal article reviews the literature on therapeutic applications of taurine. Taurine is a conditionally essential amino acid that is not utilized in protein synthesis, but rather is found free or in simple peptides. In vivo studies in various species have shown taurine to be essential in certain aspects of mammalian development, and have demonstrated an association between low levels of taurine and various pathological lesions including cardiomyopathy, retinal degeneration, and growth retardation. Taurine's metabolic actions include bile acid conjugation, detoxification, membrane stabilization, osmoregulation, and modulation of cellular calcium levels. Clinically, taurine has been used with varying degrees of success in the treatment of such conditions as cardiovascular disease, hypercholesterolemia, cystic fibrosis, detoxification, hepatic disorders, alcoholism, ocular disorders, epilepsy, Alzheimer's disease, and diabetes. The article has 2 figures and 60 references.

·

Alternative Medicine Update Source: Alternative Health Practitioner: The Journal of Complementary and Natural Care. 3(3): 157-160. Fall/Winter 1997. Summary: This journal article reports the results of 12 studies funded by the Office of Alternative Medicine in 1993 and 1994. The studies were classified as either mind/body interventions or as pharmacological or biological treatments. The 10 mind/body intervention studies include the following therapies: biofeedback, dance movement therapy, guided imagery, hypnotic imagery, music therapy, prayer, and yoga. Conditions studied include pain, diabetes mellitus, cystic fibrosis, asthma, immunity, cancer, AIDS, brain injury, and drug abuse. The two pharmacological and biological studies were 'Enzyme Therapy and Experimental Memory Metastasis' and 'Pharmacological Treatment of Cancer by Antioxidants.'.

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·

Chronic Pain in Cystic Fibrosis Source: Pediatrics. 98(4): 741-747. October 1996. Summary: This journal article describes a study of the incidence and treatment of chronic pain in patients with cystic fibrosis (CF). Researchers examined the medical records of two groups of patients followed at the CF Center of Children's Hospital in Boston, Massachusetts. One group consisted of 55 patients over age 5 years (mean age 26 years) who died between 1984 and 1993, and the second group consisted of 23 additional patients who had been referred to the Hospital's Pain Treatment Center. The incidence of pain was 84 percent in the first group and 100 percent in the second group. The most commonly reported symptoms were chest pain (65 percent) and headaches (55 percent); back pain (19 percent), abdominal pain (19 percent), and limb pain (17 percent) also were reported. Fifty-two percent of the chest pain cases were musculoskeletal. The main etiologies of headache were hypercarbia or hypoxia, migraine, and sinusitis. More than half of the patients had one or more trials of transcutaneous electrical nerve stimulation, acupuncture, relaxation techniques, or biofeedback for pain control. Fifty-three percent of the patients had pain severe enough to require opioid treatment, and 13 patients received opioids for more than 3 months. Regional analgesia was effective in eight patients with more severe pain. The article has 2 figures, 6 tables, and 32 references.

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 parents to search for articles that specifically relate to cystic fibrosis 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 “cystic fibrosis” (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 cystic fibrosis: ·

A comprehensive exercise program for persons with cystic fibrosis. Author(s): Rose J, Jay S. Source: J Pediatr Nurs. 1986 October; 1(5): 323-34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3639937&dopt=Abstract

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·

A disciplined approach to spiritual care giving for adults living with cystic fibrosis. Author(s): Palmer C. Source: J Health Care Chaplain. 2001; 11(1): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11398539&dopt=Abstract

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A model for group intervention with the chronically ill: cystic fibrosis and the family. Author(s): Brown DG, Krieg K, Belluck F. Source: Soc Work Health Care. 1995; 21(1): 81-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8553194&dopt=Abstract

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A therapeutic trial of fatty acid supplementation in cystic fibrosis. Author(s): Elliott RB. Source: Pediatrics. 1976 April; 57(4): 474-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1264542&dopt=Abstract

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Acute lymphoblastic leukaemia in a child with cystic fibrosis. Author(s): Rizzari C, Conter V, Jankovic M, D'Angelo P, Masera G, Costantini D, Bettinelli ME, Giunta AM. Source: Haematologica. 1992 September-October; 77(5): 427-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1483594&dopt=Abstract

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Acute respiratory distress due to vocal cord dysfunction in cystic fibrosis. Author(s): Rusakow LS, Blager FB, Barkin RC, White CW. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 1991; 28(6): 443-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1744030&dopt=Abstract

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Acute respiratory infection in patients with cystic fibrosis with mild pulmonary impairment: comparison of two physiotherapy regimens. Author(s): Williams MT, Parsons DW, Frick RA, Ellis ER, Martin AJ, Giles SE, Grant ER.

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Source: Aust J Physiother. 2001; 47(4): 227-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11722291&dopt=Abstract ·

Airway clearance techniques in the treatment of cystic fibrosis. Author(s): McIlwaine MP, Davidson AG. Source: Current Opinion in Pulmonary Medicine. 1996 November; 2(6): 447-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9363183&dopt=Abstract

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Allergy in cystic fibrosis nurses to pancreatic extract. Author(s): Lipkin GW, Vickers DW. Source: Lancet. 1987 February 14; 1(8529): 392. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2880202&dopt=Abstract

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Autogenic drainage: a modern approach to physiotherapy in cystic fibrosis. Author(s): Schoni MH. Source: Journal of the Royal Society of Medicine. 1989; 82 Suppl 16: 32-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2657053&dopt=Abstract

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Behavioral interventions and stress management training for hospitalized adolescents and young adults with cystic fibrosis. Author(s): Spirito A, Russo DC, Masek BJ. Source: General Hospital Psychiatry. 1984 July; 6(3): 211-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6378718&dopt=Abstract

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Benefits of music therapy as an adjunct to chest physiotherapy in infants and toddlers with cystic fibrosis. Author(s): Grasso MC, Button BM, Allison DJ, Sawyer SM. Source: Pediatric Pulmonology. 2000 May; 29(5): 371-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10790249&dopt=Abstract

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Beta-carotene supplementation in cystic fibrosis. Author(s): Winklhofer-Roob BM.

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Source: The Journal of Pediatrics. 1996 July; 129(1): 181-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8757591&dopt=Abstract ·

Bronchial asthma due to allergy to pancreatic extract: a hazard in the treatment of cystic fibrosis. Author(s): Sakula A. Source: Br J Dis Chest. 1977 October; 71(4): 295-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=588432&dopt=Abstract

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Changes in body composition and muscle protein degradation during nutritional supplementation in nutritionally growth-retarded children with cystic fibrosis. Author(s): Shepherd RW, Thomas BJ, Bennett D, Cooksley WG, Ward LC. Source: Journal of Pediatric Gastroenterology and Nutrition. 1983; 2(3): 439-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6620051&dopt=Abstract

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Chest physiotherapy in cystic fibrosis: a comparative study of autogenic drainage and the active cycle of breathing techniques with postural drainage. Author(s): Miller S, Hall DO, Clayton CB, Nelson R. Source: Thorax. 1995 February; 50(2): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7701456&dopt=Abstract

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Chest physiotherapy in cystic fibrosis: improved tolerance with nasal pressure support ventilation. Author(s): Fauroux B, Boule M, Lofaso F, Zerah F, Clement A, Harf A, Isabey D. Source: Pediatrics. 1999 March; 103(3): E32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10049988&dopt=Abstract

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Chest physiotherapy--the mechanical approach to antiinfective therapy in cystic fibrosis. Author(s): Zach MS, Oberwaldner B.

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Source: Infection. 1987; 15(5): 381-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3319913&dopt=Abstract ·

Children with cystic fibrosis benefit from massage therapy. Author(s): Hernandez-Reif M, Field T, Krasnegor J, Martinez E, Schwartzman M, Mavunda K. Source: Journal of Pediatric Psychology. 1999 April; 24(2): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10361400&dopt=Abstract

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Cholesterol esterase activities in commercial pancreatic enzyme preparations and implications for use in pancreatic insufficient cystic fibrosis. Author(s): Walters MP, Conway SP. Source: Journal of Clinical Pharmacy and Therapeutics. 2001 December; 26(6): 425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11722679&dopt=Abstract

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Cimetidine as an adjunct to oral enzymes in the treatment of malabsorption due to cystic fibrosis. Author(s): de Bieville F, Neijens HJ, Fernandes J, van Caillie M, Kerrebijn KF. Source: Acta Paediatr Scand. 1981 January; 70(1): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6908433&dopt=Abstract

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Colloid and crystal formation in parotid saliva of cystic fibrosis patients and non-cystic fibrosis subjects. I. Physicochemistry. Author(s): Allars HM, Blomfield J, Rush AR, Brown JM. Source: Pediatric Research. 1976 June; 10(6): 578-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=818608&dopt=Abstract

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Colloid and crystal formation in parotid saliva of cystic fibrosis patients and non-cystic fibrosis subjects. II. Electron microscopy and electrophoresis. Author(s): Allars HM, Cockayne DJ, Blomfield J, Rush AR, Van Lennep EW, Brown JM.

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Source: Pediatric Research. 1976 June; 10(6): 584-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=818609&dopt=Abstract ·

Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in adult cystic fibrosis patients. Author(s): Gan KH, Heijerman HG, Geus WP, Bakker W, Lamers CB. Source: Alimentary Pharmacology & Therapeutics. 1994 December; 8(6): 603-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7696449&dopt=Abstract

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Cystic fibrosis and the role of the physical therapist in its management. Author(s): Tecklin JS, Holsclaw DS. Source: Physical Therapy. 1973 April; 53(4): 386-94. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4693291&dopt=Abstract

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Cystic fibrosis in Russia: background and a model for future collaboration with the West. Author(s): Kapranov N, Ginter E, Kashirskaja N, Hill CM, Ilangovan P, Rolles CJ. Source: Journal of the Royal Society of Medicine. 1996; 89 Suppl 27: 44-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8778450&dopt=Abstract

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Cystic fibrosis. Author(s): Morony T. Source: Prog Phys Ther. 1970; 1(3): 220-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=5523596&dopt=Abstract

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Cystic fibrosis: what is involved in the home treatment program for these children, adolescents and young adults? Author(s): Selekman J. Source: Pediatric Nursing. 1977 March-April; 3(2): 32-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=584356&dopt=Abstract

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Deficiency of vitamins E and A in cystic fibrosis is independent of pancreatic function and current enzyme and vitamin supplementation. Author(s): Lancellotti L, D'Orazio C, Mastella G, Mazzi G, Lippi U. Source: European Journal of Pediatrics. 1996 April; 155(4): 281-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8777920&dopt=Abstract

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Detection of cystic fibrosis delta F508 mutation by anti-doublestranded DNA antibody. Author(s): Hopfer SM, Makowski GS, Davis EL, Aslanzadeh J. Source: Ann Clin Lab Sci. 1995 November-December; 25(6): 475-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8572556&dopt=Abstract

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Development and evaluation of a multi-family psychoeducational program for cystic fibrosis. Author(s): Goldbeck L, Babka C. Source: Patient Education and Counseling. 2001 August; 44(2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11479059&dopt=Abstract

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Development of the role-play inventory of situations and coping strategies for parents of children with cystic fibrosis. Author(s): Quittner AL, Tolbert VE, Regoli MJ, Orenstein DM, Hollingsworth JL, Eigen H. Source: Journal of Pediatric Psychology. 1996 April; 21(2): 209-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8920154&dopt=Abstract

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Dietary supplement and nutrition in children with cystic fibrosis. Author(s): Berry HK, Kellogg FW, Hunt MM, Ingberg RL, Richter L, Gutjahr C. Source: Am J Dis Child. 1975 February; 129(2): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1091138&dopt=Abstract

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Differential stimulation of cytosolic phospholipase A2 by bradykinin in human cystic fibrosis cell lines. Author(s): Berguerand M, Klapisz E, Thomas G, Humbert L, Jouniaux AM, Olivier JL, Bereziat G, Masliah J.

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Source: American Journal of Respiratory Cell and Molecular Biology. 1997 October; 17(4): 481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9376123&dopt=Abstract ·

Edetate sodium aerosol in Pseudomonas lung infection in cystic fibrosis. Author(s): Brown J, Mellis CM, Wood RE. Source: Am J Dis Child. 1985 August; 139(8): 836-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3927708&dopt=Abstract

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Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial. Author(s): Merli M, Bertasi S, Servi R, Diamanti S, Martino F, De Santis A, Goffredo F, Quattrucci S, Antonelli M, Angelico M. Source: Journal of Pediatric Gastroenterology and Nutrition. 1994 August; 19(2): 198-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7815243&dopt=Abstract

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Effect of abnormal liver function on vitamin E status and supplementation in adults with cystic fibrosis. Author(s): Stead RJ, Muller DP, Matthews S, Hodson ME, Batten JC. Source: Gut. 1986 June; 27(6): 714-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3721295&dopt=Abstract

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Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients. Author(s): Portal B, Richard MJ, Ducros V, Aguilaniu B, Brunel F, Faure H, Gout JP, Bost M, Favier A. Source: Clinical Chemistry. 1993 June; 39(6): 1023-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8504531&dopt=Abstract

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Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients. Author(s): Portal B, Richard MJ, Coudray C, Arnaud J, Favier A.

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Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1995 January 31; 234(1-2): 137-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7758213&dopt=Abstract ·

Effect of pancreatic extracts on the faecal excretion and on the serum concentration of cobalamin and cobalamin analogues in cystic fibrosis. Author(s): Gueant JL, Vidailhet M, Pasquet C, Djalali M, Nicolas JP. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1984 February 14; 137(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6697525&dopt=Abstract

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Effect of taurine supplementation on fat and bile acid absorption in patients with cystic fibrosis. Author(s): Colombo C, Arlati S, Curcio L, Maiavacca R, Garatti M, Ronchi M, Corbetta C, Giunta A. Source: Scand J Gastroenterol Suppl. 1988; 143: 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3164502&dopt=Abstract

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Effect of taurine supplementation on fat and energy absorption in cystic fibrosis. Author(s): De Curtis M, Santamaria F, Ercolini P, Vittoria L, De Ritis G, Garofalo V, Ciccimarra F. Source: Archives of Disease in Childhood. 1992 September; 67(9): 1082-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1417050&dopt=Abstract

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Effect of taurine supplements on fat absorption in cystic fibrosis. Author(s): Darling PB, Lepage G, Leroy C, Masson P, Roy CC. Source: Pediatric Research. 1985 June; 19(6): 578-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4011338&dopt=Abstract

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Effect of taurine supplements on growth, fat absorption and bile acid on cystic fibrosis. Author(s): Carrasco S, Codoceo R, Prieto G, Lama R, Polanco I. Source: Acta Univ Carol [med] (Praha). 1990; 36(1-4): 152-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2130680&dopt=Abstract

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·

Effect of the addition of protease inhibitors to sputa from cystic fibrosis patients. Author(s): Costello CM, McQuaid K, O'Connor CM, Fitzgerald MX. Source: Biochemical Society Transactions. 1994 February; 22(1): 53S. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8206281&dopt=Abstract

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Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients. Author(s): Beker LT, Ahrens RA, Fink RJ, O'Brien ME, Davidson KW, Sokoll LJ, Sadowski JA. Source: Journal of Pediatric Gastroenterology and Nutrition. 1997 May; 24(5): 512-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9161943&dopt=Abstract

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Effect on renal function of essential fatty acid supplementation in cystic fibrosis. Author(s): Strandvik B, Berg U, Kallner A, Kusoffsky E. Source: The Journal of Pediatrics. 1989 August; 115(2): 242-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2754552&dopt=Abstract

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Effects of beta-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis. Author(s): Renner S, Rath R, Rust P, Lehr S, Frischer T, Elmadfa I, Eichler I. Source: Thorax. 2001 January; 56(1): 48-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11120904&dopt=Abstract

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Effects of calcium on intestinal mucin: implications for cystic fibrosis. Author(s): Forstner JF, Forstner GG. Source: Pediatric Research. 1976 June; 10(6): 609-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1272637&dopt=Abstract

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Effects of long-term oral beta-carotene supplementation on lipid peroxidation in patients with cystic fibrosis. Author(s): Rust P, Eichler I, Renner S, Elmadfa I.

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Source: Int J Vitam Nutr Res. 1998; 68(2): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9565821&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to cystic fibrosis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

General Overview Cystic Fibrosis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cystic_Fibrosis.htm

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Cystic Fibrosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html ·

Alternative Therapy Hypnotherapy Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsModalities/Hypnot herapycm.html Massage Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsModalities/Massag ecm.html

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Herbs and Supplements Anise Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Beta-Carotene Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Blue Flag Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Borago Alternative names: Borage; Borago officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Hyperlink: http://www.herbmed.org/ Cayenne Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Cobalamin Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cystic_Fibrosis.htm Cysteine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Dandelion Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Digestive Enzymes Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Enzymes.htm Eicosapentaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cystic_Fibrosis.htm Elecampane Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Goldenseal Source: Integrative Medicine Communications; www.onemedicine.com

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Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Herbal Medicine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Horseradish Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Hyssop Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Indian Tobacco Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Licorice Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Lipase Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cystic_Fibrosis.htm Lipase Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Lipase.htm

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Lipase Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Parsley Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Rosemary Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Taurine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cystic_Fibrosis.htm Thyme Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html Wild Indigo Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/CysticF ibrosiscc.html ·

Related Conditions Liver Cirrhosis

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Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Liver_Cirrhosis.htm Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Malabsorption.htm Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Pancreatic_Insufficie ncy.htm

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): ·

Healthy Child, Whole Child: Integrating the Best of Conventional and Alternative Medicine to Keep Your Kids Healthy by Stuart H. Ditchek, M.D. and Russell H. Greenfield; Paperback - 464 pages (June 2002), Harper Resource; ISBN: 0062737465; http://www.amazon.com/exec/obidos/ASIN/0062737465/icongroupinterna

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Alternative Medicine for Dummies by James Dillard (Author); Audio Cassette, Abridged edition (1998), Harper Audio; ISBN: 0694520659; http://www.amazon.com/exec/obidos/ASIN/0694520659/icongroupinterna

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Complementary and Alternative Medicine Secrets by W. Kohatsu (Editor); Hardcover (2001), Hanley & Belfus; ISBN: 1560534400; http://www.amazon.com/exec/obidos/ASIN/1560534400/icongroupinterna

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Dictionary of Alternative Medicine by J. C. Segen; Paperback-2nd edition (2001), Appleton & Lange; ISBN: 0838516211; http://www.amazon.com/exec/obidos/ASIN/0838516211/icongroupinterna

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Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating by Walter C. Willett, MD, et al; Hardcover - 352 pages (2001), Simon & Schuster; ISBN: 0684863375; http://www.amazon.com/exec/obidos/ASIN/0684863375/icongroupinterna

· Encyclopedia of Natural Medicine, Revised 2nd Edition by Michael T. Murray, Joseph E. Pizzorno; Paperback - 960 pages, 2nd Rev edition (1997), Prima Publishing; ISBN: 0761511571; http://www.amazon.com/exec/obidos/ASIN/0761511571/icongroupinterna ·

Integrative Medicine: An Introduction to the Art & Science of Healing by Andrew Weil (Author); Audio Cassette, Unabridged edition (2001), Sounds True; ISBN: 1564558541; http://www.amazon.com/exec/obidos/ASIN/1564558541/icongroupinterna

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New Encyclopedia of Herbs & Their Uses by Deni Bown; Hardcover - 448 pages, Revised edition (2001), DK Publishing; ISBN: 078948031X; http://www.amazon.com/exec/obidos/ASIN/078948031X/icongroupintern a

· Textbook of Complementary and Alternative Medicine by Wayne B. Jonas; Hardcover (2003), Lippincott, Williams & Wilkins; ISBN: 0683044370; http://www.amazon.com/exec/obidos/ASIN/0683044370/icongroupinterna For additional information on complementary and alternative medicine, ask your child’s doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Cardiomyopathy: A disease of the heart muscle (myocardium). [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU]

Gestation: The period of development of the young in viviparous animals,

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from the time of fertilization of the ovum until birth. [EU] Hypnotic: A drug that acts to induce sleep. [EU] 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] Stabilization: The creation of a stable state. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH]

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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements for cystic fibrosis. Any dietary recommendation is based on age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with cystic fibrosis may be given different recommendations. Some recommendations may be directly related to cystic fibrosis, while others may be more related to general health. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of cystic fibrosis. We will then show you how to find studies dedicated specifically to nutrition and cystic fibrosis.

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Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·

Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.

·

Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

·

Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.

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Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.

Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your child’s diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·

Vitamin A is important to the health of eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.

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Vitamin B1, also known as thiamine, is important for the nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.

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Vitamin B2, also known as riboflavin, is important for the nervous system and muscles, but is also involved in the release of proteins from

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nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·

Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains

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Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.

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Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.

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Vitamin C allows the body’s immune system to fight various medical conditions, strengthens body tissue, and improves the body’s use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.

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Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.

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Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.

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Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.

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Folic Acid maintains healthy cells and blood; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.

It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·

Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.

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Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.

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·

Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.

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Iodine helps regulate the body’s use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.

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Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.

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Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.

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Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.

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Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.

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Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.

The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, the doctor may encourage deviations from the average official recommendation based on your child’s specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/lab-cons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:52 ·

DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.

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DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.

52

Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.

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·

RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”

·

RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?53

Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”54 According to the ODS, dietary supplements can have an important impact on the prevention and management of medical conditions and on the maintenance of health.55 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where the use of plant products, in particular, has a long tradition. However, the This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 54 Contact: The Office of Dietary Supplements, National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: (301) 435-2920, Fax: (301) 480-1845, E-mail: [email protected]. 55 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 53

264 Cystic Fibrosis

overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of Dietary Supplements National Institutes of Health Building 31, Room 1B29 31 Center Drive, MSC 2086 Bethesda, Maryland 20892-2086 Tel: (301) 435-2920 Fax: (301) 480-1845 E-mail: [email protected]

Finding Studies on Cystic Fibrosis The NIH maintains an office dedicated to nutrition and diet. The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.56 IBIDS is available to the public free of charge through the ODS Internet page: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back periodically as this database is frequently updated. More studies can be Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture. 56

Researching Nutrition 265

found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “cystic fibrosis” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following is a typical result when searching for recently indexed consumer information on cystic fibrosis: ·

Identification and treatment of cystic fibrosis-related diabetes. A survey of current medical practice in the U.S. Author(s): Department of Pediatrics, Tufts University School of Medicine, Boston, Massachusetts, USA. [email protected] Source: Allen, H F Gay, E C Klingensmith, G J Hamman, R F DiabetesCare. 1998 June; 21(6): 943-8 0149-5992

·

Nutrition in cystic fibrosis. Source: Schorah, C.J. Smithells, R.W. Nutr-Res-Rev. Cambridge [England] Cambridge University Press. 1991. volume (4) page 51-67. 0954-4224

·

Nutrition support in cystic fibrosis. Source: Gerson, W T Swan, P Walker, W A Nutr-Revolume 1987 December; 45(12): 353-60 0029-6643

·

Taurine supplementation in cystic fibrosis. Source: Anonymous Nutr-Revolume 1988 July; 46(7): 257-8 0029-6643

·

Vitamin E therapy in cystic fibrosis. Source: Anonymous Nutr-Revolume 1988 August; 46(8): 289-90 0029-6643

The following information is typical of that found when using the “Full IBIDS Database” when searching using “cystic fibrosis” (or a synonym): ·

Percutaneous endoscopic gastrostomy feeding in patients with cystic fibrosis. Author(s): Department of Gastroenterology, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 (United Kingdom) Source: Williams, S.G.J. Ashworth, F. McAlweenie, A. Poole, S. Hodson, M.E. Westaby, D. (United-Kingdom). (1999). volume 44(1) page 87-90. mankind respiratory diseases human nutrition supplementary feeding feeding extrabuccal feeding nutritional status pathogenesis body weight physiological functions Summary: genre humain maladie respiratoire nutrition humaine alimentation complementaire alimentation alimentation artificielle etat nutritionnel pathogenese poids corporel fonction physiologique

266 Cystic Fibrosis

Additional physician-oriented references include: ·

13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis. Author(s): Department of Pediatrics, University of Modena, Italy. Source: Amarri, S Harding, M Coward, W A Evans, T J Weaver, L T JPediatr-Gastroenterol-Nutr. 1999 September; 29(3): 327-31 0277-2116

·

A comparison of enteric coated microspheres with enteric coated tablet pancreatic enzyme preparations in cystic fibrosis. A controlled study. Author(s): Hospital for Sick Children, London, UK. Source: Vyas, H Matthew, D J Milla, P J Eur-J-Pediatr. 1990 January; 149(4): 241-3 0340-6199

·

A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency. Author(s): Rainbow Babies & Children's Hospital, Cleveland, Ohio 44106, USA. Source: Stern, R C Eisenberg, J D Wagener, J S Ahrens, R Rock, M doPico, G Orenstein, D M Am-J-Gastroenterol. 2000 August; 95(8): 1932-8 00029270

·

Actions of genistein on cystic fibrosis transmembrane conductance regulator channel gating. Evidence for two binding sites with opposite effects. Author(s): Department of Physiology, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri 65211, USA. Source: Wang, F Zeltwanger, S Yang, I C Nairn, A C Hwang, T C J-GenPhysiol. 1998 March; 111(3): 477-90 0022-1295

·

Altered calcium homeostasis in adults with cystic fibrosis. Author(s): Division of Pulmonary Medicine, University of North Carolina, Chapel Hill 27599-7524, USA. [email protected] Source: Aris, R M Lester, G E Dingman, S Ontjes, D A Osteoporos-Int. 1999; 10(2): 102-8 0937-941X

·

Benign intracranial hypertension in an older child with cystic fibrosis. Author(s): Department of Gastroenterology, Hospital Bambino Gesu, Rome, Italy. Source: Lucidi, V Di Capua, M Rosati, P Papadatou, B Castro, M PediatrNeurol. 1993 Nov-December; 9(6): 494-5 0887-8994

Researching Nutrition 267

·

Bisphosphonates for osteoporosis in people with cystic fibrosis (Cochrane Review). Author(s): Community Health and Epidemiology, Dalhousie University, 5849 University Avenue, Halifax, Nova Scotia, CANADA, B3H 4H7. [email protected] Source: Brenckmann, C Papaioannou, A Cochrane-Database-SystRevolume 2001; 4: CD002010 1469-493X

·

Central pontine and extrapontine myelinolysis presenting with parkinsonism in a patient with cystic fibrosis. Author(s): National Hospital for Neurology and Neurosurgery, London, UK. Source: Prevett, M C Rossor, M N Mov-Disord. 1999 May; 14(3): 523-5 0885-3185

·

Current approaches to the nutritional management of cystic fibrosis in Australia. Author(s): Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia. Source: Anthony, H Catto Smith, A Phelan, P Paxton, S J-Paediatr-ChildHealth. 1998 April; 34(2): 170-4 1034-4810

·

Cystic fibrosis and the pancreas: recent scientific advances. Author(s): Department of Pediatrics-Gastroenterology, Aristotle University of Thessaloniki, Greece. Source: Nousia Arvanitakis, S J-Clin-Gastroenterol. 1999 September; 29(2): 138-42 0192-0790

·

Cystic fibrosis transmembrane conductance regulator (CFTR) confers glibenclamide sensitivity to outwardly rectifying chloride channel (ORCC) in Hi-5 insect cells. Author(s): Station de Recherche de Pathologie Comparee INRA-CNRS 30180 Saint-Christol-lez-Ales F-30380, France. Source: Julien, M Verrier, B Cerutti, M Chappe, V Gola, M Devauchelle, G Becq, F J-Membr-Biol. 1999 April 1; 168(3): 229-39 0022-2631

·

Defective ATP-dependent mucin secretion by cystic fibrosis pancreatic epithelial cells. Author(s): Groupe de Recherche sur les Glandes Exocrines, Faculte de Medecine, Marseille, France. Source: Montserrat, C Merten, M Figarella, C FEBS-Lett. 1996 September 16; 393(2-3): 264-8 0014-5793

·

DNA enzyme immunoassay: a rapid and convenient colorimetric method for diagnosis of cystic fibrosis. Author(s): Consiglio Nazionale delle Ricerche (CNR), Medical School, University of Brescia, Italy.

268 Cystic Fibrosis

Source: Mazza, C Mantero, G Primi, D Mol-Cell-Probes. 1991 December; 5(6): 459-66 0890-8508 ·

Early onset of essential fatty acid deficiency in patients with cystic fibrosis receiving a semisynthetic diet. Source: Parsons, Howard G. Shillabeer, Gillian Rademaker, Alfred W. JPediatr. St. Louis : C.V. Mosby. December 1984. volume 105 (6) page 958961. ill., charts. 0022-3476

·

Effect of taurine supplements on growth, fat absorption and bile acid on cystic fibrosis. Author(s): Department of Pediatrics, Children's Hospital La Paz, Autonoma University, Madrid, Spain. Source: Carrasco, S Codoceo, R Prieto, G Lama, R Polanco, I Acta-UnivCarol-[Med]-(Praha). 1990; 36(1-4): 152-6 0001-7116

·

Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance. Author(s): Kinderklinik der RWTH Aachen, Germany. Source: Kentrup, H Bongers, H Spengler, M Kusenbach, G Skopnik, H Eur-J-Pediatr. 1999 June; 158(6): 455-9 0340-6199

·

Energy intakes and low-fat diets in children with cystic fibrosis. [editorial]. Source: Pencharz, P.B. J-Pediatr-Gastroenterol-Nutr. New York : Raven Press. August 1983. volume 2 (3) page 400-401. 0277-2116

·

Energy needs and growth in children with cystic fibrosis. Source: Parsons, H.G. Beaudry, P. Dumas, A. Pencharz, P.B. J-PediatrGastroenterol-Nutr. New York : Raven Press. 1983. volume 2 (1) page 4449. ill., charts. 0277-2116

·

Enteral nutrition for patients with cystic fibrosis: comparison of a semielemental and nonelemental formula. Author(s): Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, Denver, USA. Source: Erskine, J M Lingard, C D Sontag, M K Accurso, F J J-Pediatr. 1998 February; 132(2): 265-9 0022-3476

·

Enteral tube feeding for cystic fibrosis. Author(s): Cystic Fibrosis Department, Seacroft Hospital, York Road, Leeds, Yorkshire, UK, LS14 6UH. Source: Conway, S P Morton, A Wolfe, S Cochrane-Database-SystRevolume 2000; (2): CD001198 1469-493X

Researching Nutrition 269

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

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

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

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

·

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

·

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

·

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

·

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

·

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

270 Cystic Fibrosis

·

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

·

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

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Carbohydrates: A nutrient that supplies 4 calories/gram. They may be simple or complex. Simple carbohydrates are called sugars, and complex carbohydrates are called starch and fiber (cellulose). An organic compound—containing carbon, hydrogen, and oxygen—that is formed by photosynthesis in plants. Carbohydrates are heat producing and are classified as monosaccharides, disaccharides, or polysaccharides. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Percutaneous:

Performed through the skin, as injection of radiopacque

Researching Nutrition 271

material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [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] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Thermoregulation: Heat regulation. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH]

Finding Medical Libraries 273

APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.57

57

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

274 Cystic Fibrosis

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

Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):58 ·

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

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM

·

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

·

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

·

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

·

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

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

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

58

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

Finding Medical Libraries 275

·

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

·

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

·

California: San José PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

·

California: University of California, Davis. Health Sciences Libraries

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

·

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

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

·

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

·

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

·

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

·

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

·

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

·

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

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

·

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

276 Cystic Fibrosis

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

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

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

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

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

Finding Medical Libraries 277

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

278 Cystic Fibrosis

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

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Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

Finding Medical Libraries 279

·

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

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

·

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

·

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

·

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

·

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

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

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

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Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

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South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

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

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Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html

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

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

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APPENDIX E. NIH CONSENSUS STATEMENT ON GENETIC TESTING FOR CYSTIC FIBROSIS Overview NIH Consensus Development Conferences are convened to evaluate available scientific information and resolve safety and efficacy issues related to biomedical technology. The resultant NIH Consensus Statements are intended to advance understanding of the technology or issue in question and to be useful to health professionals and the public.59 Each NIH consensus statement is the product of an independent, non-Federal panel of experts and is based on the panel’s assessment of medical knowledge available at the time the statement was written. Therefore, a consensus statement provides a “snapshot in time” of the state of knowledge of the conference topic. The NIH makes the following caveat: “When reading or downloading NIH consensus statements, keep in mind that new knowledge is inevitably accumulating through medical research. Nevertheless, each NIH consensus statement is retained on this website in its original form as a record of the NIH Consensus Development Program.”60 The following concensus statement was posted on the NIH site and not indicated as “out of date” in March 2002. It was originally published, however, in April 1997.61

This paragraph has been adapted from the NIH: http://odp.od.nih.gov/consensus/cons/cons.htm. 60 Adapted from the NIH: http://odp.od.nih.gov/consensus/cons/consdate.htm. 61 Genetic Testing for Cystic Fibrosis. NIH Consensus Statement Online 1997 Apr 14-16 [cited 2002, February, 15];15(4): 1-37: http://consensus.nih.gov/cons/106/106_statement.htm. 59

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Abstract Objective To provide health care providers, patients, and the general public with a responsible assessment of the optimal practices for genetic testing for cystic fibrosis (CF). Participants A non-Federal, nonadvocate, 14-member panel representing the fields of genetics, obstetrics, internal medicine, nursing, social work, epidemiology, pediatrics, psychiatry, genetic counseling, bioethics, health economics, health services research, law, and the public. In addition, 21 experts from these same fields presented data to the panel and a conference audience of 500.

Evidence The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience.

Consensus Process The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference.

Conclusions Genetic testing for CF should be offered to adults with a positive family history of CF, to partners of people with CF, to couples currently planning a pregnancy, and to couples seeking prenatal testing. The panel does not recommend offering CF genetic testing to the general population or newborn

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infants. The panel advocates active research to develop improved treatments for people with CF and continued investigation into the understanding of the pathophysiology of the disease. Comprehensive educational programs targeted to health care professionals and the public should be developed using input from people living with CF and their families and from people from diverse racial and ethnic groups. Additionally, genetic counseling services must be accurate and provide balanced information to afford individuals the opportunity to make autonomous decisions. Every attempt should be made to protect individual rights, genetic and medical privacy rights, and to prevent discrimination and stigmatization. It is essential that the offering of CF carrier testing be phased in over a period of time to ensure that adequate education and appropriate genetic testing and counseling services are available to all persons being tested.

What Is Genetic Testing for Cystic Fibrosis? Genetic testing is available for a variety of diseases and will soon be available for many more. Furthermore, genetic predispositions to common diseases are becoming known and potentially will affect large segments of the population. This consensus conference considered cystic fibrosis (CF), a well-characterized, serious genetic disease for which testing is becoming available, and a series of recommendations for genetic testing in the population is presented. The analysis and recommendations may prove relevant to genetic testing in other situations. At the beginning of this decade, a test was developed that could identify individuals who carry the genetic mutation associated with CF. Concerned that this test might be inappropriately or prematurely used, several genetic and health professional organizations issued recommendations on its use. These groups considered the circumstances under which the tests should be offered and the populations that would potentially benefit. Almost all of their recommendations were against using the test for large-scale, population-based screening until more sensitive tests were developed and until more had been learned about the risks and benefits of genetic testing for individuals and their families. Several statements called for additional support for research on the educational, laboratory, counseling, ethical, and cost/benefit issues associated with the delivery of population-based screening for CF. Since that time, new research has yielded a large body of data on these issues.

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This conference brought together the research investigators, health care providers, epidemiologists, geneticists, ethicists, and other experts, as well as representatives of the public, to present and discuss the latest data. Following 1-1/2 days of presentations by experts and audience discussion, an independent, non-Federal consensus panel composed of experts in the fields of genetics, obstetrics, internal medicine, nursing, social work, epidemiology, pediatrics, psychiatry, genetic counseling, bioethics, health economics, health services research, law, and the public weighed the scientific evidence and developed a draft statement in response to the following five key questions: ·

What is the current state of knowledge regarding natural history, epidemiology, genotype-phenotype correlations, treatment, and genetic testing of cystic fibrosis in various populations?

·

What has been learned about genetic testing for cystic fibrosis regarding (public and health professional) knowledge and attitudes, interest and demand, risks and benefits, effectiveness, cost, and impact?

·

Should cystic fibrosis carrier testing be offered to: (1) individuals with a family history of cystic fibrosis; (2) adults in the preconception or prenatal period; and/or (3) the general population?

·

What are the optimal practices for cystic fibrosis genetic testing (setting, timing, and the practices of education, consent, and counseling)?

·

What should be the future directions for research relevant to genetic testing for cystic fibrosis and, more broadly, for research and health policies related to genetic testing?

The primary sponsors of this meeting are the National Human Genome Research Institute and the NIH Office of Medical Applications of Research. The conference is cosponsored by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; the National Institute of Child Health and Human Development; the NIH Office of Rare Diseases; the National Institute of Mental Health; the National Institute of Nursing Research; the NIH Office of Research on Women’s Health; the Agency for Health Care Policy and Research; and the Centers for Disease Control and Prevention.

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The Current State of Knowledge CF is a multisystem genetic disease in which defective chloride transport across membranes causes dehydrated secretions. This leads to tenacious mucus in the lungs, to mucus plugs in the pancreas, and to the characteristically high sweat chloride levels. Intelligence and cognitive function are typically normal. A survey in 1995 reported that 35 percent of young adults with CF worked full-time, and almost 90 percent had completed a high school education. More than 25,000 Americans have CF, with approximately 850 individuals newly diagnosed each year. CF is inherited as an autosomal recessive disorder; the responsible gene, the CF transmembrane conductance regulator (CFTR), was mapped to chromosome 7 and identified in 1989.

Natural History CF has a highly variable presentation and course. Median age at diagnosis is 6-8 months; nearly two-thirds of individuals are diagnosed before 1 year of age. Some individuals have severe pulmonary and/or gastrointestinal disease, whereas others have relatively mild disease with presentation during adolescence and young adulthood. Outcomes range from early death from pulmonary complications to mild atypical disease in the second and third decades, and a rare normal length of life. Even though median survival increased from 18 years in 1976 to 30.1 years in 1995, there has been little lifespan extension between 1990 and 1995. Survival has improved, thus far, through aggressive management of pulmonary, pancreatic, and intestinal complications. Despite advances in treatment, there is no cure for CF. Severity of lung disease is the key to the quality of and length of life. Ninety percent of persons who have CF die from pulmonary complications. Pulmonary function tests, especially forced expiratory volume (FEV1), are predictive of mortality: when the FEV1is less than or equal to 30 percent, mortality is 50 percent in 2 years. Poor prognosis is related to respiratory complications before 1 year of age, malnutrition, and denial of the condition. Better prognosis is indicated from mild symptoms at diagnosis, pancreatic sufficiency, and atypical presentation. There are suggestions in the literature that early diagnosis and treatment may result in improved growth of young children; however, data are limited about whether early treatment decreases morbidity as measured by hospitalizations and pulmonary function tests and, ultimately, mortality rates.

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Treatment The major goals of traditional treatment of CF are to improve pulmonary, gastrointestinal, and pancreatic outcomes. Pulmonary treatment is focused on physical therapy to decrease obstruction of the airways, antibiotics to decrease colonization by Staphylococcus aureus and Pseudomonas aeruginosa, and nonsteroidal anti-inflammatory drugs to decrease the inflammatory cascade and resulting tissue damage. Gastrointestinal and pancreatic treatments include high protein-high caloric diets, pancreatic enzymes, and fat-soluble vitamins. New modalities include the use of inhaled DNase, which breaks down the DNA from neutrophils, and pharmacologic modification of ion transport to loosen secretions. Pharmacologic activation of mutant CFTR protein to stimulate chloride channel activity is being investigated. Double lung transplantation extends life, but is not curative. There are new findings regarding human beta defensin-1, a factor responsible for innate immunity. The natural bactericidal activity of human beta defensin-1 is inhibited on CF epithelia because of high extracellular sodium chloride, and correction of the sodium chloride concentration of extracellular fluid holds promise for therapy in CF. Finally, although the feasibility of gene therapy is currently under investigation, this potential “cure” is not anticipated in the near future.

Epidemiology Incidence CF is one of the most common genetic diseases in Caucasians, with an incidence of about 1 in 3,300. The disease also has a fairly high incidence among Hispanics, 1 in 9,500. CF is a rare disorder in native Africans and native Asians, estimated to occur in less than 1 in 50,000, but higher incidences are observed in American populations of these ethnic groups (1 in 15,300 and 1 in 32,100, respectively), suggesting Caucasian admixture. Recent surveys of some Native- American populations also indicate high incidences: 1 in 3,970 in the Pueblo people, and 1 in 1,580 among the Zuni. The relatively high incidence and concomitant high frequency of carriers motivate the proposal of population-based screening.

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CF Mutation Analysis Since the identification of the gene and the major mutation responsible for CF, more than 600 mutations and DNA sequence variations have been identified in the CFTR gene. The Delta F508 mutation is represented in almost all populations, although its relative frequency varies among different geographic locations. The highest frequency is observed in Caucasian populations, where it accounts for approximately 70 percent of the CF alleles (Table 1). Delta F508 mutation accounts for large portions of the alleles in other racial/ethnic groups: 48 percent in African-Americans, 46 percent in Hispanics, and 30 percent in Asian-Americans and Ashkenazi Jews. Some 15-20 other “common” mutations account for 2-15 percent of CF alleles, depending on the ethnic composition of the patient group studied. Most of the remaining mutations are rare. The proportion of detectable mutations is an important indicator of the utility of a population-screening program. Combining detection of the Delta F508 with other mutations common to specific ethnic groups, it appears that there are several populations for which 90-95 percent sensitivity can now be achieved with the current technology: Ashkenazi Jews, Celtic Bretons, French Canadians from Quebec, and some Native Americans. In Caucasians in the United States, it is feasible to approach 90 percent sensitivity at the current time. The detection rate in African-Americans is about 75 percent. Despite the relatively high incidence in Hispanics, the detectable alleles account for only 57 percent of the CF mutations in this group. The promise appears to be weak in Asian-Americans, at 30 percent sensitivity. Because the remaining mutations are rare, expanding the panel of screened mutations is expected to achieve only marginal gains in sensitivity. Genotype-Phenotype Correlations The discovery of the gene has enabled evaluation of specific mutations in relation to the observed clinical heterogeneity. The correlation of genotype with phenotype is substantial for pancreatic function; however, identification of the specific CFTR mutation has not been highly predictive of the severity and course of pulmonary disease, which is the major factor affecting patient quality of life and longevity. Furthermore, there is evidence to suggest a role for modifier genes and environmental factors that are as yet unidentified. Virtually all males with classic CF have congenital bilateral absence of the vas deferens (CBAVD). However, there is a population of otherwise healthy

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males with CBAVD who have a high frequency of CF mutations. It appears that more than half of these males have one or two specific mutations, which identifies these genotypes as the most common cause of CBAVD. Some women with these genotypes are normal or develop chronic sinusitis or bronchitis as the extent of their morbidity. It is unclear whether such mildly affected individuals can be reliably identified by their genotype. Thus, it appears that knowledge of the genotype is as yet of limited value in making predictions about the anticipated course of disease in an individual, although research to identify genotypes associated with relatively mild presentation such as CBAVD may prove useful in informed decision making.

Genetic Testing in Various Populations Genetic testing has been performed for CF carriers in various racial and ethnic groups, mass and focused screening, and different types of organized medical settings. At this time, there is limited spontaneous public request for this testing. Although testing has not met with enthusiasm, there has been little or no group opposition to offering testing to African-Americans, AsianAmericans, Caucasians, Hispanics, Native Americans, and persons of Jewish ancestry. Most experience has been gained with Caucasians and Ashkenazi Jews, where incidence is highest. Mass screening has resulted in the least response. Pregnant patients appear to be motivated to obtain genetic information. Nonpregnant patients and those with a family history have exhibited only moderate acceptance rates. In the United States, mass screening of newborns has occurred in only two states, Colorado and Wisconsin; otherwise, newborn testing has been limited to those with a family history. The logistics of testing have been successfully implemented in various settings such as HMOs and primary care settings, including feefor-service settings. With the exception of one fee-for-service setting and the newborn state programs, all testing has been free of charge. Direct provider recruitment has proven more effective than less personal approaches.

What Has Been Learned about Genetic Testing Knowledge and Attitudes Toward Cystic Fibrosis and Genetic Testing As with most genetic diseases, the public’s knowledge is very low regarding CF, its genetic basis, and its variable course and prognosis, and

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understanding of genetic testing is poor. Moreover, among those who have heard of CF, inaccurate impressions often exist, because people are generally not familiar with the progress in treating the disease over the past 40 years. Understanding genetic testing for CF involves learning complex concepts such as test sensitivity, carrier status, patterns of inheritance, risk/probability, and genotype-phenotype correlations. These gaps in the public’s genetic knowledge suggest that genetic testing programs must include written informed consent and educational and counseling components. There are only approximately 2,000 genetic professionals nationally, so implementation of widespread genetic testing must rely heavily on primary care providers and prenatal providers. Some research efforts, however, have shown that many office-based physicians are not interested in participating in genetic testing programs involving CF because of lack of familiarity and concerns with unreimbursed time. Medical practitioners need to become more knowledgeable about genetics, genetic testing, and nondirective counseling as genetic tests become more widely available. Public Interest and Demand Notwithstanding the limits of public understanding of genetics and genetically related diseases, prospective parents have enormous interest in the health and well-being of children to be. In an Office of Technology Assessment survey of a decade ago, 83 percent of Americans said they would take a genetic test before having children, if it would tell them whether their children would likely inherit a fatal genetic disease. Many genetic counselors and nurse geneticists report that they are frequently asked about DNA-based CF tests. However, studies have shown that interest in CF genetic testing is limited in the general population, and that agreement to participate in genetic education and testing procedures occurs primarily among pregnant women and persons with positive family histories. In the prenatal testing context, participation rates have varied widely in studies to date because of variability of methods used, with acceptance of offers for testing ranging from about 50 percent to a high of 78 percent in one HMO population. Participation has been affected by factors relating to convenience, education, cost, views regarding abortion, concerns about the low sensitivity of the test, and the manner of presentation of the testing opportunity. Concerns about confidentiality and insurability are often mentioned in the genetic testing context. There also is evidence of reluctance to engage in carrier testing on the psychological grounds of “not wanting to

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know,” as has occurred in studies where some people with positive family histories chose not to participate. The reasons for interest in prenatal genetic testing are diverse. Some participants in studies have sought information in anticipation of a decision about pregnancy termination in the case of a fetus with CF. Others wished to know only their carrier status, perhaps to make emotional and practical plans for parenting a child with CF. Risks Research has assessed initial concerns among providers of genetic services that genetic testing might have adverse psychological consequences, such as anxiety and depression caused by the difficulty of conveying the uncertainties inherent in genetic testing or the challenge of adjusting to identification as a carrier. The research to date has shown such problems to be transitory; the topic, nevertheless, may warrant additional research incorporating comprehensive psychological assessment tools. The risks of misinformation or misunderstanding highlight the need for a high level of competence in conveying the results and meaning of information derived from genetic testing. Problems retaining complex genetic concepts highlight the need for broad-based public education. Another concern is the fear that disclosure of genetic test results might affect one’s family relationships, employment, educational or other opportunities, or ability to maintain or obtain health insurance. This is a more general problem and needs to be addressed at a broader level to ensure patient access to genetic services and other opportunities without threat of harmful consequences.

Impact and Effectiveness The effectiveness of genetic testing can be judged in terms of its ability to convey information that patients find useful. The experience to date reports high levels of patient satisfaction after undergoing genetic testing for CF. In the prenatal situation, because of the rarity of the disease, over 99 percent of couples tested receive reassuring information regarding the improbability of having a child with CF. Several studies have reported significant increases in knowledge of CF among couples who have undergone genetic testing and participated in the educational programs connected with it. Although there was some drop in

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knowledge after several years, knowledge levels still were higher than in the pretesting period. A decline in understanding has been reported in some research, where a considerable portion of the individuals who were carriers did not retain the meaning of the test results. In some instances, this meant that people incorrectly believed they were no longer at risk for having offspring with CF. In addition to the educational and psychological benefits of CF testing, the effectiveness of testing can be judged in terms of how the information is used. This is most germane in situations in which a test produced a positive result. Most couples in whom the woman was found to be a carrier chose to have the partner tested as well. The inability of current DNA testing technology to detect all possible mutations and the difficulty in conveying the concept of residual risk temper these positive effects. Another indicator of impact occurs in the rare instances in which a fetus with CF is identified. In the limited studies to date, most couples with no positive family history in this circumstance choose to terminate the pregnancy. It should be noted that some couples do not undergo final stages of testing because of their intention to continue the pregnancy. Cost Assessment of the costs associated with testing, screening, and treatment of CF is challenging because technology and treatment modalities are changing rapidly. Nonetheless, there is general agreement about the magnitude of many of the key cost variables and the likely future direction of change in these costs. In terms of treatment, options for care for many individuals with CF have expanded over the past decade with implications for the average cost of care. Although the Office of Technology Assessment estimated in 1992, based on 1989 data, that the annual treatment costs were approximately $10,000 per year per individual with CF, current estimates exceed $40,000 per year in direct medical costs and $9,000 per year in ancillary costs. Using a 3 percent discount rate, this implies a net present value of approximately $800,000 for direct and ancillary costs associated with a CF birth. The technology and cost of DNA diagnostic testing for a CF mutation are changing rapidly. At present, the cost of DNA diagnostic testing for CF is between $50 and $150 per test, testing for between 6 and 72 CF mutations. Rapid progress is being made in cost of testing, however, because of

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improvements in instrumentation. These costs will likely decline and the number of mutations screened will quickly increase. In terms of the cost of prenatal testing, the costs of informed consent procedures, educational and counseling services, associated administrative costs, and so forth must be added to the laboratory testing costs per se. These costs will vary as a function of the level of various educational and counseling services accompanying the testing according to evolving professional standards for genetic testing procedures. Regarding cost savings from neonatal testing, currently no definitive data demonstrate medical benefit and cost savings associated with populationbased neonatal screening. However, there is suggestive evidence that differences in height, weight, and nutrition of youngsters with CF are a function of whether they had neonatal screening and early diagnoses. These may well translate into future health outcomes and treatment savings, but the magnitude of such benefits is not known. Broader assessment of the costs of a voluntary, broad-based prenatal screening program depends on variables such as the number of individuals deciding to participate in the test, the incidence of CF carriers in the population involved, the testing method (e.g., sequential or couple-based), the proportion of couples with an affected fetus who choose to terminate the pregnancy, and the number of children the couples wish to have. Although assumptions about these variables differed, studies showed that the cost per identified CF fetus averted ranged from $250,000 to $1,250,000 for a Caucasian population of Northern European ancestry. Estimates on the high end of this range come down substantially if one considers couples who plan to have more than one child or if identified carriers inform siblings and other relatives. A broad educational effort is essential to create a level of genetic literacy in the population and among health care professionals that will allow individuals to utilize genetic and other information in making important life decisions. An estimate of the costs of this effort is not available.

Cystic Fibrosis Carrier Testing The first two sections of this appendix summarized the knowledge base for the recommendations that follow. Objectives for CF testing and reasons for and against testing are different for each population, but in all cases

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individuals’ acceptance of testing must be entirely voluntary. Each population is considered separately. ·

Individuals with a family history of CF and partners of those with CF should be offered genetic testing. As a group, individuals with a family history have relatively high frequencies of mutations in the CFTR gene. Members of this group have increased awareness of their risk of being carriers, as well as increased familiarity with the disease and its impact on the family. Testing can be helpful with regard to reproductive decision making and informative regarding family health.

·

CF genetic testing should be offered to the prenatal population and couples currently planning a pregnancy, particularly those in high-risk populations. Data indicate that a significant level of interest in CF testing exists in this group. Because this is a vulnerable population and because of the inherent time constraints, it is particularly important that they receive adequate and balanced information. The information includes, but is not limited to, sensitivity of the test, a description of the range of severity of the disease, and risks. The offer of testing should be made to enable couples who wish to avoid the birth of a child with CF to do so, without influencing those who do not. Care should be taken to ensure that the decision to have testing is completely voluntary.

·

CF testing for the general population is not advocated. Given the low incidence and prevalence of CF and the demonstrable lack of interest in the general population, there is little justification for testing.

·

Routine genetic screening for CF in newborns is not advocated, based on available data. Studies have not provided sufficient evidence that identifying CF patients earlier than the current average age of diagnosis improves outcomes. The panel recommends that studies of CFTR screening in newborns be developed to provide a foundation for assessment of benefits of early therapy.

·

Education and informed consent. Genetic testing for CF should begin with education concerning CF. It should be clear that the patient has received the material and has had an opportunity for questions to be answered before testing is undertaken. Development of model educational and consent forms for genetic testing, as well as education programs for providers, is encouraged. All persons undergoing genetic testing should give written informed consent for the test, receive culturally sensitive educational materials, and demonstrate an understanding of the test and test results.

·

It is essential that the offering of CF carrier testing be phased in over a period of time to ensure that adequate education and appropriate genetic testing and counseling services are available to all persons being tested.

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·

Genetic testing and counseling for CF in the populations identified by the panel’s recommendations should be eligible for payment by insurers.

Optimal Practices for Cystic Fibrosis Genetic Testing The goal of genetic testing for CF is to provide individuals with information that will permit them to make informed reproductive and other decisions. Testing is of benefit only if there is access to the necessary comprehensive health services and resources that ensue from case/carrier detection. Components of a testing program should include education, counseling, and the use of medical facilities to improve health outcomes. The setting must provide access for provision of comprehensive services. Whether it is based in a medical center or in a primary care setting, a professional interdisciplinary team should address the individual’s genetic, medical, emotional, and reproductive health needs. The services should not be administered in isolation, but in association with tertiary care centers. The complexity of DNA diagnostic data and the vast number of mutations in CF mandate sophisticated laboratory capability (or access to it) as an integral component. Laboratories providing molecular diagnostic capability should utilize tests that achieve a mutation detection rate of approximately 90 percent or better for Caucasians or a detection rate for African-Americans, Asian-Americans, Hispanics, Ashkenazi Jews, Native Americans, and others comparable to that available at present.

Timing for Testing Depends on Targeted Group ·

In adults with a positive family history of CF, genetic testing should be provided at any time requested.

·

Newborn siblings of patients with CF as well as other siblings who exhibit atypical symptoms should be tested. However, testing of minors for the purpose of identifying carrier status is not recommended.

·

Carrier detection in pregnant couples with a family history of CF should be provided in an expeditious manner. Similarly, the request by a couple with known carrier status for prenatal diagnosis must be addressed promptly to facilitate access to all needed services so as to provide an optimal opportunity to make an informed decision.

·

Couples in the prenatal population (i.e., those not in a high-risk group) should be offered the opportunity for carrier detection as early as

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possible to provide them time to consider the full range of informed reproductive decisions. ·

The rationale for offering testing to couples currently planning a pregnancy is predicated on timely provision of balanced, accurate information about CF, including natural history of the disease, relative frequency in different ethnic and racial groups, variability of disease manifestation, and availability of highly sensitive and specific tests to determine carrier status.

·

Although most males who have CF are sterile, partners of persons with CF should be tested on request for carrier status. The highest practical level of sensitivity of the DNA test should be used to maximize detection of at-risk couples.

Education Genetic testing should be provided in response to the needs of patients. Thus, programs must provide information relating to genetics in general such as basic inheritance patterns, variable nature of disease expression, risk of occurrence, and diagnostic and therapeutic options. In the case of CF testing programs, balanced information should be presented and regularly updated. The elements that must be included are: ·

Natural history of the disease

·

Range of severity

·

Improvement in survival rates

·

Quality of life for patients and families

·

Full range of therapeutic modalities

·

Reproductive options, including adoption, use of artificial reproductive modalities, and continuation or termination of pregnancy

Educating patients and families can be accomplished by utilizing a wide variety of printed materials and media, including videos and interactive online systems. At present, information content is presented in a variable manner. It is recommended that effort be directed to develop model information that highlights the positive as well as the negative aspects of living with CF, using input from people living with the disease, their families, and members from diverse racial/ethnic groups.

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Every attempt should be made to ascertain the level of understanding and cultural background of the person being tested. Followup assessment to determine retention of knowledge is an essential ingredient of any educational program.

Informed Consent To ensure informed choice, it is imperative that the informed consent process demonstrate that the individual has fully understood the multiple options and implications that ensue from genetic testing. It is also important to ensure that those who decline to be tested do so knowledgeably, although this is typically not documented. Informed consent must include a clear description of the disease, of the limitations of the genetic testing methods, and of the voluntary participation of the individual giving consent. Individuals must be assured that although every effort will be made to ensure the confidentiality of their medical and genetic data, absolute confidentiality cannot be guaranteed.

Counseling Provision of accurate genetic counseling, particularly when the results are provided to the patient or when the intervention strategies are discussed, is essential. The implications of genetic testing, its limitations and strengths, and the risks of ensuing potential therapies and interventions mandate that individuals knowledgeable in genetics provide these services. The counseling skills required must combine respect for a patient’s right to make an autonomous decision with an appropriate level of support to facilitate the decision making process. Any strategy attempting to provide these services to the public carries with it a responsibility to enhance the educational process for physicians and other health care providers. Rapid changes in the methodology of molecular diagnosis, and therapeutic options that result from them, mandate continuing education and involvement of genetic specialists in the process of translating these developments into practical and beneficial terms. CF centers should make counseling available to minor siblings who often have a need for information that goes unaddressed.

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Nondiscrimination Pivotal to individual autonomy is the guarantee that genetic data not be used for discrimination with reference to insurability, employment and educational opportunities, and social stigmatization. Federal and State statutes currently in place to address nondiscriminatory practices against any carrier, person with a genetic disorder, or family member need to be enforced. However, these laws provide limited protection from discriminatory practices. Additional Federal and State statutes are needed to broaden protection from harm based on genetic status from educational, health care, and other organizations that may impact on and restrict immediate and long-term opportunities. Special attention to expand the understanding and awareness of the legal, insurance, health care, and educational professions about discriminatory practices should be undertaken. In spite of laws that are put into place to protect people from external discrimination, less visible or more subtle harm may occur. For example, families may perceive differently a member found to be a carrier or found to be affected with a genetic disorder. These families may marginalize or ostracize the identified person. No laws can be passed to provide protection from this practice; however, future research is needed to understand the parameters of this problem and the moderating impact of education and counseling.

Future Directions for Research ·

As treatment options and screening technologies change, what are the impacts on medical costs, ancillary costs, and quality of life associated with CF? What are the cost-effective approaches to treatment and screening in different settings?

·

What is the actual incidence of discrimination and stigmatization with respect to carriers, persons with genetic disorders, and their families? How does fear or anticipation of discrimination impact decision making by some persons with identified genetic disorders?

·

What is the most effective mechanism to educate health professionals about the current state of genetic disorders, genetic testing, and management of genetic disorders?

·

What are effective educational strategies to educate the public and specific populations about genetics and genetic testing?

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·

What are patients’ expectations of pretest education, genetic reproductive risk counseling, genetic evaluations, and transmittal of test results?

·

Do early diagnosis and treatment of newborn infants with CF modify the morbidity as indicated by pulmonary function tests, maturation status, rates of infection, hospitalization, and mortality rates?

·

A variety of screening strategies have been used in various studies (e.g., sequential versus couple screening). A systematic literature review should be undertaken, and, if warranted, a randomized controlled trial should be initiated to assess the relative merits of these strategies.

·

Certain specific mutations appear to result in limited phenotypes, such as CBAVD. A goal of future research should be to continue to identify additional mutations, modifier genes, and environmental factors, and correlate these with the phenotype.

·

Because CF is characterized by multiple mutations of the CFTR gene, this disease would be the prototype for the assessment of multiple methodologies to define numerous allelic mutations of a large gene.

·

The optimal system for delivery of genetic services in rural and nonacademic settings should be studied.

·

What are long-term effects of pregnancy termination or continuation on high-risk couples?

Conclusions and Recommendations ·

Active research should continue on improved treatments for people with CF, enhanced molecular diagnosis of CF, and better understanding of the pathophysiology of CF.

·

Over the past two decades, aggressive management of the pulmonary manifestations of CF and new treatment modalities have resulted in much longer survival.

·

More than 90 percent of CF mutations can be identified in certain populations. Although generally good correlations exist between certain CF mutations and pancreatic status, it is known that CF mutations are not robust predictors of severity of disease and longevity.

·

The goal of genetic testing is to provide individuals with information that will permit them to make informed decisions.

·

CF genetic testing should be offered to adults with a positive family history of CF, to partners of people with CF, to couples currently planning a pregnancy, and to couples seeking prenatal testing.

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·

Comprehensive educational programs are recommended, utilizing a variety of media, for health care professionals and the public.

·

Counseling services must be accurate and provide balanced information to afford individuals the opportunity to make autonomous decisions. Every attempt should be made to protect individual rights and genetic and medical privacy rights and to prevent discrimination and stigmatization.

·

Access to genetic testing in the prenatal setting enhances the ability of couples to make reproductive choices, as shown by their interest in and use of the information they gain. The cost is reasonable in relation to the benefits obtained.

·

Offering CF genetic testing to the general population or to newborn infants is not recommended.

·

Genetic testing for many additional conditions will be available in the future. Some of the principles considered for CF genetic testing might well have broader application.

·

It is essential that the offering of CF carrier testing be phased in over a period of time in order to ensure that adequate education and appropriate genetic testing and counseling services are available to all persons being tested.

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

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

·

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

·

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

·

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

·

On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

·

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

·

Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a) and drkoop.com (http://www.drkoop.com/). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to cystic fibrosis and keep them on file. The NIH, in particular, suggests that parents of children with cystic fibrosis visit the following Web sites in the ADAM Medical Encyclopedia:

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·

Basic Guidelines for Cystic Fibrosis Cystic fibrosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000107.htm Cystic fibrosis - nutritional considerations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002437.htm Cystic fibrosis - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002176.htm

·

Signs & Symptoms for Cystic Fibrosis Abdominal distention Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003122.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Breathing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Clubbing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003282.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Coughing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm

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Delayed growth Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003021.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Discouraged Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Easy fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Foul smelling stools Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003132.htm Hemoptysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003073.htm Lung disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000066.htm Osteoarthropathy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003282.htm

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Stools, pale or clay colored Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003129.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Tachypnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm Wheezing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003070.htm ·

Diagnostics and Tests for Cystic Fibrosis Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm CAT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Chest CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003788.htm

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Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Diffusing capacity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003854.htm Echocardiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Fecal fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003588.htm Pulmonary function Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003443.htm Pulmonary function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003853.htm Secretin stimulation test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003892.htm Sweat chloride Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003630.htm Sweat test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003630.htm

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Trypsin and chymotrypsin in stool Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003594.htm Upper GI and small bowel series Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003816.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm ·

Nutrition for Cystic Fibrosis Fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm Fats Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm Normal growth and development Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002456.htm Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm Vitamins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002399.htm Yogurt Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002463.htm

·

Surgery and Procedures for Cystic Fibrosis

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Lung transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003010.htm ·

Background Topics for Cystic Fibrosis Bile Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002237.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Cystic fibrosis - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002176.htm Distal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002346.htm Meconium Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002262.htm Pain reliever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm Percussion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002281.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm

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

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

·

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

·

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

·

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

Glossary 309

CYSTIC FIBROSIS GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Pertaining to the abdomen. [EU] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abortion: 1. the premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. premature stoppage of a natural or a pathological process. [EU] Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas

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and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: A antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] 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] Alveolitis: Inflammation of the alveoli. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Angioneurotic: Denoting a neuropathy affecting the vascular system; see angioedema. [EU] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Antibiotic: A drug that kills or inhibits the growth of bacteria. [NIH] Antibodies: Specific proteins produced by the body's immune system that bind with foreign proteins (antigens). [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant:

One of many widely used synthetic or natural substances

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added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Anus: The distal or terminal orifice of the alimentary canal. [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] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Ascites: Effusion and accumulation of serous fluid in the abdominal cavity; called also abdominal or peritoneal dropsy, hydroperitonia, and hydrops abdominis. [EU] Aspiration: The act of inhaling. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any H-isomer. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Berylliosis: A lung disease resulting from exposure to beryllium metal. [NIH] Beryllium: Beryllium. An element with the atomic symbol Be, atomic number 4, and atomic weight 9.01218. Short exposure to this element can lead to a type of poisoning known as berylliosis. [NIH] Bezoars: Concretions of swallowed hair, fruit or vegetable fibers, or similar substances found in the alimentary canal. [NIH] Bilateral: Having two sides, or pertaining to both sides. [EU] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and

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electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Bronchiectasis: Chronic dilatation of the bronchi marked by fetid breath and paroxysmal coughing, with the expectoration of mucopurulent matter. It may effect the tube uniformly (cylindric b.), or occur in irregular pockets (sacculated b.) or the dilated tubes may have terminal bulbous enlargements (fusiform b.). [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and air passages. [NIH] Bronchoscopy: A technique for visualizing the interior of bronchi and instilling or removing fluid or tissue samples by passing a lighted tube (bronchoscope) through the nose or mouth into the bronchi. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Carbohydrates: A nutrient that supplies 4 calories/gram. They may be simple or complex. Simple carbohydrates are called sugars, and complex carbohydrates are called starch and fiber (cellulose). An organic compound—containing carbon, hydrogen, and oxygen—that is formed by photosynthesis in plants. Carbohydrates are heat producing and are classified as monosaccharides, disaccharides, or polysaccharides. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiomyopathy: A disease of the heart muscle (myocardium). [NIH]

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Cardiovascular: Pertaining to the heart and blood vessels. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cell: Basic subunit of every living organism; the simplest unit that can exist as an independent living system. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] Cholangiography: Roentgenography of the biliary ducts after administration or injection of a contrast medium, orally, intravenously or percutaneously. [EU] Cholangitis: Inflammation of a bile duct. [EU] Cholecystectomy: present. [NIH]

Surgical removal of the gallbladder and gallstones, if

Cholecystitis: Inflammation of the gallbladder, caused primarily by gallstones. Gallbladder disease occurs most often in obese women older than 40 years of age. [NIH] Cholelithiasis: The presence or formation of gallstones. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH] Cholinergic: Resembling acetylcholine in pharmacological stimulated by or releasing acetylcholine or a related compound. [EU]

action;

Chromosomal: Pertaining to chromosomes. [EU] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU] Colic: Paroxysms of pain. This condition usually occurs in the abdominal

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region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [EU] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Constipation: Infrequent or difficult evacuation of the faeces. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: The prevention of conception or impregnation. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crystallization: The formation of crystals; conversion to a crystalline form. [EU]

Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytomegalovirus: A genus of the family herpesviridae, subfamily betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH] Decongestant: An agent that reduces congestion or swelling. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. Called also anhydration, deaquation and hypohydration. [EU] Dentists: Individuals licensed to practice dentistry. [NIH] Dermatitis: Inflammation of the skin. [EU]

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Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU]

DEXA: A method (dual energy X-ray absortiometry) used to estimate total body fat and percent of body fat. Potential disadvantages include whole body radiation and the long time required for scanning while the subject lies on a hard table. [NIH] Dietetics: The study and regulation of the diet. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diverticulitis: Inflammation of a diverticulum, especially inflammation related to colonic diverticula, which may undergo perforation with abscess formation. Sometimes called left-sided or L-sides appendicitis. [EU] Duodenum: The first or proximal portion of the small intestine, extending from the pylorus to the jejunum; so called because it is about 12 fingerbreadths in length. [EU] Dysplasia: Abnormal development or growth. [NIH] Dyspnea: Shortness of breath; difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: A test that bounces sound waves off the heart to produce pictures of its internal structures. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents, characterized in the acute stage by erythema, edema associated with a serous exudate between the cells of the epidermis (spongiosis) and an inflammatory infiltrate in the dermis, oozing and vesiculation, and crusting and scaling; and in the more chronic stages by lichenification or thickening or both, signs of excoriations, and hyperpigmentation or hypopigmentation or both. Atopic dermatitis is the most common type of dermatitis. Called also eczematous dermatitis. [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] Electrocardiogram: [NIH]

Measurement of electrical activity during heartbeats.

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Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Emphysema: Chronic lung disease in which there is permanent destruction of alveoli. [NIH] Encephalopathy: Any degenerative disease of the brain. [EU] Encopresis: Incontinence of feces not due to organic defect or illness. [NIH] 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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Developing or originating within the organisms or arising from causes within the organism. [EU] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Enema: A clyster or injection; a liquid injected or to be injected into the rectum. [EU] Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH] 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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warmblooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exocrine: 1. secreting outwardly, via a duct;. [EU]

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Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH] Fetus: Unborn offspring from 7 or 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Process by which inflamed tissue becomes scarred. [NIH] Fistula: An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body; frequently designated according to the organs or parts with which it communicates, as anovaginal, brochocutaneous, hepatopleural, pulmonoperitoneal, rectovaginal, urethrovaginal, and the like. Such passages are frequently created experimentally for the purpose of obtaining body secretions for physiologic study. [EU] Flatulence: The presence of excessive amounts of air or gases in the stomach or intestine, leading to distention of the organs. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The entire genetic makeup of an individual. The fundamental constitution of an organism in terms of its hereditary factors. A group of

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organisms in which each has the same hereditary characteristics. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Glossitis: Inflammation of the tongue. [EU] Gluconeogenesis: The process by which glucose is formed from a noncarbohydrate source. [NIH] 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] Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoptysis: Coughing up blood or blood-stained sputum. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Hernia: (he protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH]

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Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Homeostasis: A tendency to stability in the normal body states (internal environment) of the organism. It is achieved by a system of control mechanisms activated by negative feedback; e.g. a high level of carbon dioxide in extracellular fluid triggers increased pulmonary ventilation, which in turn causes a decrease in carbon dioxide concentration. [EU] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [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] Hyperthermia: Abnormally high body temperature, especially that induced for therapeutic purposes. [EU] Hypnotic: A drug that acts to induce sleep. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoxia: Too little oxygen available to meet the needs of the body’s tissues. [NIH]

Ibuprofen:

A nonsteroidal anti-inflammatory agent with analgesic

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properties used in the therapy of rheumatism and arthritis. [NIH] Idiopathic: Results from an unknown cause. [NIH] Ileus: Obstruction of the intestines. [EU] 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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU]

Incontinence: Inability to control excretory functions, as defecation (faecal i.) or urination (urinary i.). [EU] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: Response of the body tissues to injury; typical signs are swelling, redness, and pain. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: The act of taking food, medicines, etc., into the body, by mouth. [EU]

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

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of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Pertaining to the intestine. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH]

Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood

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serum. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH] Keloid: A sharply elevated, irregularly- shaped, progressively enlarging scar due to the formation of excessive amounts of collagen in the corium during connective tissue repair. [EU] Lavage: To wash the interior of a body organ. [NIH] Legionellosis: Infections with bacteria of the genus legionella. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] 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] Lipodystrophy: 1. any disturbance of fat metabolism. 2. a group of conditions due to defective metabolism of fat, resulting in the absence of subcutaneous fat, which may be congenital or acquired and partial or total. Called also lipoatrophy and lipodystrophia. [EU] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is lithotripsy, laser. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU]

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Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Lymphedema: Edema due to obstruction of lymph vessels or disorders of the lymph nodes. [NIH] Lymphocytic: Pertaining to, characterized by, or of the nature of lymphocytes. [EU] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [EU] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of tumours. [EU] Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: A microscopic organism; those of medical interest include bacteria, viruses, fungi and protozoa. [EU] Microspheres: Small uniformly-sized spherical particles frequently labeled with radioisotopes or various reagents acting as tags or markers. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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]

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Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, ...): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucus: A thick fluid produced by the lining of some organs of the body. [NIH]

Mycobacterium: An organism of the genus Mycobacterium. [EU] Nasal: Pertaining to the nose. [EU] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [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] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neutropenia: Leukopenia in which the decrease in white blood cells is chiefly in neutrophils. [EU] Neutrophil: Having an affinity for neutral dyes. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and

Glossary 325

nucleic acids and found in all living cells. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU]

Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the islets of langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancrelipase: A preparation of hog pancreatic enzymes standardized for lipase content. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU]

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Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH] 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] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. the act of boring or piercing through a part. 2. a hole made through a part or substance. [EU] Peridural: Around or external to the dura mater. [EU] 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] Perioperative: Pertaining to the period extending from the time of hospitalization for surgery to the time of discharge. [EU] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH]

Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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]

Glossary 327

Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Placenta: The special tissue that joins the mother to her fetus; it provides the fetus with oxygen, water, and nutrients (food) from the mother's blood and secretes the hormones necessary for successful pregnancy. [NIH] Plague: An acute infectious disease caused by yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plasminogen: The inactive precursor of plasmin (=enzyme that catalyses the hydrolysis of peptide bonds at the carbonyl end of lysine or arginine residues). [EU] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Podiatry: A specialty concerned with the diagnosis and treatment of foot disorders and injuries and anatomic defects of the foot. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Porphyria: A pathological state in man and some lower animals that is often due to genetic factors, is characterized by abnormalities of porphyrin metabolism, and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: Occurring after a surgical operation. [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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Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]

Prenatal: Occurring before birth. [NIH] Preoperative: Preceding an operation. [EU] Prevalence: The number of events, e.g., instances of a given disease or other condition, in a given population at a designated time. When used without qualification, the term usually refers to the situation at specific point in time (point prevalence). Prevalence is a number, not a rate. [NIH] Proctitis: Inflammation of the rectum. [EU] Progressive: Increasing in severity. [NIH] Prolapse: 1. the falling down, or sinking, of a part or viscus; procidentia. 2. to undergo such displacement. [EU] Prophylaxis: The prevention of disease; preventive treatment. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Proteolytic: 1. pertaining to, characterized by, or promoting proteolysis. 2. an enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteus: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the intestines of humans and a wide variety of animals, as well as in manure, soil, and polluted waters. Its species are pathogenic, causing urinary tract infections and are also considered secondary invaders, causing septic lesions at other sites of the body. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: 1. itching; an unpleasant cutaneous sensation that provokes the desire to rub or scratch the skin to obtain relief. 2. any of various conditions marked by itching, the specific site or type being indicated by a modifying term. [EU] Pseudomonas:

A genus of gram-negative, aerobic, rod-shaped bacteria

Glossary 329

widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Ptosis: 1. prolapse of an organ or part. 2. drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [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] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Radiotherapy: The treatment of disease by ionizing radiation. [EU] 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] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectal: Pertaining to the rectum (= distal portion of the large intestine). [EU] Reflux: A backward or return flow. [EU] Reoperation: A repeat operation for the same condition in the same patient. It includes reoperation for reexamination, reoperation for disease progression or recurrence, or reoperation following operative failure. [NIH] Resection: Excision of a portion or all of an organ or other structure. [EU] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: Process of exchanging oxygen from the air for carbon dioxide from the body; includes the mechanical process of breathing, gas exchange, and oxygen and carbon dioxide transport to and from the cells. [NIH] Respiratory: Pertaining to respiration. [EU] Retrograde: 1. moving backward or against the usual direction of flow. 2. degenerating, deteriorating, or catabolic. [EU] Rheumatoid: Resembling rheumatism. [EU]

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Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] 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] Saline: Salty; of the nature of a salt; containing a salt or salts. [EU] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood

Glossary 331

on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Sinusitis: Inflammation of a sinus. The condition may be purulent or nonpurulent, acute or chronic. Depending on the site of involvement it is known as ethmoid, frontal, maxillary, or sphenoid sinusitis. [EU] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] 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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH]

Sputum: Matter ejected from the lungs, bronchi, and trachea, through the mouth. [EU] Stabilization: The creation of a stable state. [EU] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH]

Sterilization: 1. the complete destruction or elimination of all living microorganisms, accomplished by physical methods (dry or moist heat), chemical agents (ethylene oxide, formaldehyde, alcohol), radiation (ultraviolet, cathode), or mechanical methods (filtration). 2. any procedure by which an individual is made incapable of reproduction, as by castration, vasectomy, or salpingectomy. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the

332 Cystic Fibrosis

duodenum. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Sulfites: Inorganic salts of sulfurous acid. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH] Surgical: Of, pertaining to, or correctable by surgery. [EU] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathetic: 1. pertaining to, caused by, or exhibiting sympathy. 2. a sympathetic nerve or the sympathetic nervous system. [EU] 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] Tartrazine: An anionic, hydrophilic azo dye with an orange-yellow color used in fabrics, foods and cosmetics, and as a biological stain. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Teratogens: An agent that causes the production of physical defects in the developing embryo. [NIH] Testicular: Pertaining to a testis. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thermoregulation: Heat regulation. [EU] Thoracic: Pertaining to or affecting the chest. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [NIH] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

Glossary 333

Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]

Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Toxic: Pertaining to, due to, or of the nature of a poison or toxin; manifesting the symptoms of severe infection. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: An acute or chronic, widespread disease of animals and humans caused by the obligate intracellular protozoon Toxoplasma gondii, transmitted by oocysts containing the pathogen in the feces of cats (the definitive host), usually by contaminated soil, direct exposure to infected feces, tissue cysts in infected meat, or tachyzoites (proliferating forms) in blood. [EU] Transcutaneous: Transdermal. [EU] Translating: Conversion from one language to another language. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Urticaria: Pathology: a transient condition of the skin, usually caused by an allergic reaction, characterized by pale or reddened irregular, elevated patches and severe itching; hives. [EU] Valves: Flap-like structures that control the direction of blood flow through

334 Cystic Fibrosis

the heart. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Ventilation: The process of exchange of air between the lungs and the atmosphere leading to exchange of gases in the blood. [NIH] Vibrio: A genus of vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] Withdrawal: 1. a pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) a 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]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

·

Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna

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·

A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

·

Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

·

Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

·

Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

·

Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna

·

Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

·

Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

·

Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

336 Cystic Fibrosis

INDEX A Abdomen .............................178, 309, 331 Abdominal....... 12, 30, 97, 152, 173, 174, 175, 240, 311, 313, 317, 325 Aberrant...............................................149 Abortion .......................179, 289, 309, 334 Abscess ...............................169, 174, 315 Acidity ..................................................192 Adjuvant...............................................121 Adolescence .....12, 29, 58, 156, 285, 309, 326 Adrenergic ....86, 104, 139, 142, 179, 309, 333 Adverse .........................72, 102, 147, 290 Agonist.....................30, 86, 139, 309, 327 Airways ....... 15, 102, 116, 134, 135, 141, 145, 169, 189, 191, 193, 286 Albuterol ..................................75, 86, 309 Alendronate ...........................................66 Alleles ..........105, 141, 149, 151, 287, 318 Alopecia...............................................171 Alveoli ....................................56, 310, 316 Amniocentesis .......................................17 Anemia ............................42, 47, 171, 216 Anesthesia...........................................169 Angioneurotic.......................................169 Anthropometry .......................................39 Antibiotic ...15, 64, 89, 125, 131, 178, 195, 331, 332 Antibodies...129, 136, 137, 144, 150, 151, 316, 319, 320 Antibody...............................................246 Antimicrobial ........................................102 Antineoplastic ..............................128, 312 Anus ..............................12, 170, 173, 310 Anxiety.................................................290 Apnea ......................................36, 39, 169 Appendicitis .................................174, 315 Artery ...................................................106 Ascites .................................................167 Assay...........................................151, 320 Atypical ........................................285, 294 B Benign ...........57, 176, 178, 319, 324, 330 Benzodiazepines .................................169 Bereavement .......................................157 Beryllium ......................................128, 311 Bilateral................................................287 Bile......69, 88, 94, 96, 165, 174, 176, 239, 248, 257, 268, 312, 313, 322, 332

Biliary ... 37, 69, 87, 88, 94, 152, 165, 174, 313, 325 Bioavailability ............................ 66, 69, 74 Biochemical.... 16, 72, 130, 150, 161, 310, 326 Biomechanics ....................................... 35 Biopsy ....................... 17, 69, 97, 271, 326 Bleomycin ................................... 128, 312 Bradykinin ........................................... 246 Bronchial ............... 15, 103, 145, 175, 319 Bronchiectasis .................... 135, 142, 169 Bronchitis .............................. 49, 135, 288 Bronchodilator............................... 75, 102 Bronchopulmonary.............................. 124 Bronchoscopy ....................................... 71 C Capsules ................................. 80, 95, 263 Carbohydrates .................... 260, 270, 312 Cardiomyopathy.................................. 239 Cardiovascular ............................ 171, 239 Carotene ..................... 118, 122, 242, 249 Cell..... 13, 16, 30, 35, 43, 47, 56, 79, 88, 89, 100, 108, 123, 130, 136, 141, 149, 150, 151, 152, 156, 168, 171, 182, 192, 215, 216, 246, 309, 314, 317, 319, 321, 322, 323, 324, 329 Cerebral ...................................... 171, 209 Cervical ....................................... 178, 330 Cheilitis ............................................... 169 Cholangitis .......................................... 170 Cholecystitis................................ 166, 170 Cholelithiasis......................................... 96 Cholestasis ........................................... 96 Cholinergic .......................................... 139 Chromosomal ............... 48, 138, 146, 168 Chronic..... 11, 12, 18, 27, 31, 35, 36, 38, 45, 49, 67, 74, 78, 117, 124, 128, 138, 139, 141, 146, 149, 152, 156, 164, 169, 175, 178, 182, 210, 215, 240, 288, 313, 315, 316, 317, 325, 331, 333 Chymotrypsin ...................................... 306 Cimetidine ........................................... 121 Cirrhosis........................................ 96, 170 Colitis .................................. 165, 166, 170 Concomitant........................................ 286 Conduction.......................................... 105 Contamination..................................... 166 Cranial................................................. 101 Curative............... 178, 270, 286, 324, 330 Cyclic .......................................... 123, 139 Cytokines .............................................. 36

Index 337

Cytotoxic ................................................94 Cytotoxins ..............................................71 D Degenerative .......................174, 261, 316 Dentists................................................169 Dermatitis ............................128, 169, 315 Dermatology ........................................171 Detoxification .......................................239 Diarrhea.........12, 164, 166, 174, 260, 316 Digestion 16, 165, 177, 178, 266, 326, 331 Distal..........29, 31, 95, 130, 311, 328, 329 Diverticulitis .........................................170 Duodenum .....................87, 175, 312, 317 Dyskinesia ...........................................118 Dysplasia ...............................39, 168, 216 Dyspnea ..............................................135 Dystrophy ..............................47, 171, 215 E Efficacy .....66, 74, 76, 77, 78, 80, 81, 266, 281, 315 Electrolyte...138, 141, 146, 147, 168, 271, 327 Electrophoresis....................................244 Emphysema...........................................49 Endocarditis.................................185, 312 Endocrinology........................................43 Endogenous ........................103, 128, 315 Enterotoxins.........................167, 174, 316 Enzyme.16, 72, 80, 95, 97, 121, 126, 130, 145, 147, 148, 244, 245, 246, 266, 267, 327, 328, 332 Epithelium...35, 76, 77, 94, 100, 103, 138, 146 Epitopes.......................................136, 137 Exocrine....30, 35, 40, 41, 42, 45, 95, 122, 134, 138, 139, 144, 146, 149, 266, 325 Exogenous...............81, 88, 128, 315, 317 Exons...................................138, 151, 317 Expiration.............................................123 Extracellular.........128, 176, 286, 317, 319 F Facial ...................................................168 Faecal ..................................................248 Famotidine...........................................122 Fatal...........11, 15, 27, 135, 137, 140, 289 Fetus.17, 30, 48, 290, 291, 292, 309, 323, 327 Fibroblasts ...........................................100 Fistula ....................................57, 175, 317 Flatulence ............................................164 Flutter ..................................................118 G Gastritis ...............................................170 Gastroduodenal ...........................175, 317 Gastroenteritis .....................................164

Gastrointestinal ...... 38, 57, 95, 139, 140, 149, 166, 167, 179, 210, 270, 285, 286, 317, 334 Gastrostomy........................................ 265 Genitourinary ................................ 16, 140 Genotype ............ 102, 284, 287, 288, 289 Gestation....................................... 58, 326 Gluconeogenesis .................................. 68 Glucose............. 68, 81, 88, 268, 318, 320 Glutamine............................................ 167 Gluten ................................................. 164 Glycerol............................................... 149 H Hemoptysis ........................................... 12 Hepatic.............................. 68, 81, 94, 239 Hepatitis ........................................ 37, 170 Hepatobiliary ......................................... 96 Heredity................................................. 13 Herpes ........................................ 175, 318 Heterozygote .............................. 140, 147 Histamine ............................ 166, 185, 310 Homeostasis ....................................... 266 Hybridization ....................................... 146 Hybridomas................................. 136, 144 Hyperbilirubinemia ...................... 176, 322 Hypercalcemia ...................................... 99 Hypercholesterolemia ................. 143, 239 Hypersensitivity................................... 126 Hyperthermia ...................................... 168 Hypnotic .............................................. 239 Hypoxemia .......................................... 135 Hypoxia ............................................... 240 I Ibuprofen............................................... 80 Idiopathic................... 57, 58, 98, 319, 330 Ileus ............................................ 4, 12, 99 Immunity ............... 87, 107, 239, 286, 314 Immunization ................ 89, 257, 320, 331 Immunoassay ..................................... 267 Incontinence ....................................... 114 Incubation ........................................... 149 Indicative............................. 144, 152, 324 Induction ............................................. 100 Infertility............................................... 139 Inflammation ...... 12, 35, 57, 79, 128, 130, 152, 173, 174, 175, 188, 189, 190, 192, 219, 311, 313, 315, 317, 320, 321, 325, 330 Influenza ............................................. 210 Ingestion ............................. 177, 263, 327 Inhalation .............. 62, 102, 134, 177, 327 Insulin.............................. 81, 88, 318, 321 Interstitial....... 49, 100, 128, 130, 313, 330 Intestinal..... 12, 16, 30, 95, 129, 135, 165, 166, 167, 171, 174, 175, 249, 260, 285, 316, 318, 323

338 Cystic Fibrosis

Intestines ..12, 30, 63, 175, 177, 317, 320, 323, 328 Intravenous............................78, 177, 325 Intrinsic ................................................149 Introns..................................138, 151, 321 Invasive ...........................................79, 96 Iontophoresis .......................................139 Irritants.....................................49, 57, 321 Ischemia ..............................................164 Isoflavones ..........................................134 Isotonic ........................................139, 145 L Lavage .............................................71, 79 Legionellosis........................................169 Lethal .........29, 65, 95, 134, 142, 145, 149 Leukaemia ...........................................241 Ligament......................................177, 328 Lipid .......77, 88, 104, 119, 122, 137, 151, 178, 247, 249, 318, 321, 322, 333 Lipodystrophy ......................................170 Lipoprotein...........................................126 Liposome ...............................................73 Lubrication ...................................185, 322 Lupus .............................................49, 171 Lymphedema.......................................169 Lymphocytic.........................................210 M Malabsorption .......95, 164, 165, 166, 167, 184, 215, 244 Malformation..........................................48 Malignant ......57, 127, 128, 168, 215, 310, 311, 319 Meconium ........................................12, 99 Medicament .........................................145 Membrane ..102, 104, 110, 123, 137, 138, 146, 149, 152, 239, 321, 324 Microbiology ....................36, 87, 189, 311 Microorganism .....................................166 Microscopy ..........................................244 Microspheres .................................95, 266 Mobility ..................................................69 Molecular ....... 26, 90, 99, 101, 130, 137, 138, 141, 143, 146, 161, 207, 212, 214, 294, 296, 298, 329, 333 Mucociliary...................144, 145, 152, 324 Mucolytic........................................16, 145 Mucus ...11, 12, 15, 16, 27, 30, 35, 45, 96, 135, 136, 139, 144, 147, 149, 152, 190, 285, 324 N Nasal .....12, 17, 63, 76, 77, 219, 320, 323 Necrosis.................................58, 145, 330 Neoplasms...................127, 176, 310, 324 Neural ............................................43, 168 Neuroendocrinology ..............................43 Neurosciences.......................................43

Neutrophil........................................ 79, 80 Niacin .................................................. 261 Nitrogen ................................................ 80 Nosocomial ................................. 177, 325 O Obstetrics.................................... 282, 284 Ointments............................................ 145 Ophthalmoplegia................................. 101 Orbital ................................................. 101 Osteoporosis............. 64, 66, 87, 267, 309 Overdose ............................................ 261 P Pancreas.... 11, 12, 16, 18, 35, 40, 41, 42, 45, 63, 70, 88, 95, 121, 134, 141, 144, 152, 164, 184, 190, 267, 285, 320, 325 Pancreatin........................................... 245 Pancreatitis ......... 144, 164, 165, 166, 167 Pancrelipase ................................. 80, 266 Parenteral ........................................... 167 Parkinsonism ...................................... 267 Particle .......................................... 88, 322 Pathogenesis ................ 99, 112, 116, 265 Pathophysiology ................. 167, 283, 298 Pediatrics .............................. 36, 282, 284 Percutaneous.............................. 176, 322 Perforation .......................... 167, 174, 315 Petrolatum........................................... 145 Pharmacokinetics ........................... 76, 78 Pharmacotherapy ............................... 143 Phenotype.. 100, 101, 146, 284, 287, 289, 298 Phenylalanine ............... 16, 136, 143, 149 Phosphorylation .................. 136, 137, 141 Pilocarpine .................................... 13, 139 Placenta ................................................ 17 Plague......................................... 177, 327 Pneumoconiosis ................................. 210 Pneumonia...................... 12, 49, 190, 210 Pneumothorax ...................................... 12 Podiatry............................................... 171 Poisoning .................... 128, 175, 311, 317 Polypeptide ................................... 57, 319 Porphyria............................................. 170 Postoperative ...................................... 169 Postural................................. 15, 123, 243 Potassium ................................... 108, 262 Prenatal....... 17, 48, 138, 146, 163, 282, 284, 289, 290, 292, 293, 294, 298, 299 Prevalence .............. 75, 89, 147, 293, 328 Proctitis ............................................... 170 Progressive ..... 11, 27, 135, 152, 189, 324 Prolapse.......................... 12, 95, 130, 329 Prophylaxis ......................................... 190 Prostate....................................... 171, 215 Protease.............................................. 249

Index 339

Proteins ......13, 16, 30, 56, 57, 67, 71, 89, 100, 104, 127, 130, 136, 137, 141, 260, 262, 310, 314, 319, 323, 324, 328 Proteus ................................................166 Proximal.................99, 128, 147, 174, 315 Pruritus ..................................................74 Pseudomonas................................35, 193 Psychiatry ....................................282, 284 Ptosis ...................................................101 Purulent .........................31, 135, 145, 331 R Receptor ......................................104, 108 Recombinant ...................65, 73, 138, 146 Rectal ..............................................12, 95 Reflux ..................................................170 Reoperation .................................130, 329 Resection.....................................165, 167 Resorption ...........................................139 Respiration ........31, 56, 87, 135, 311, 329 Retrograde...........................................123 Rheology .............................................118 Rheumatoid .....................................49, 99 Riboflavin.............................................260 S Saline...................................................145 Sarcoidosis ............................49, 169, 170 Sclerosis ........................99, 168, 171, 215 Secretion ......16, 31, 43, 71, 94, 134, 136, 139, 142, 145, 167, 175, 267, 319, 330 Selenium......................................247, 262 Semisynthetic ......................................268 Serum ......69, 89, 96, 119, 152, 248, 322, 330 Sinusitis ...12, 31, 169, 192, 240, 288, 331 Skull .......................................................12 Somatic....................................29, 97, 309 Species .....58, 89, 90, 130, 153, 174, 175, 177, 179, 239, 316, 317, 328, 329, 331, 332, 333, 334 Sphincter .....................................178, 331 Spirometry .............................................79 Sputum .....13, 30, 36, 67, 71, 75, 78, 135, 145, 148, 318

Stabilization......................................... 239 Sterilization ......................................... 184 Stomach................ 56, 164, 175, 270, 317 Substrate..................................... 179, 333 Sulfites ................................................ 166 Surgical . 69, 169, 177, 270, 324, 325, 327 Sweat ... 11, 12, 13, 27, 35, 40, 41, 42, 45, 63, 69, 70, 138, 139, 141, 142, 146, 149, 190, 196, 210, 285 Systemic .... 58, 94, 95, 99, 103, 149, 169, 185, 312, 330 T Tartrazine............................................ 166 Taurine........................................ 239, 268 Teratogens............................................ 48 Testicular ............................................ 171 Thermoregulation................................ 260 Thyroxine ............................................ 262 Tobramycin ................................... 78, 193 Tolerance ...... 81, 126, 243, 266, 268, 332 Tomography.............................. 64, 68, 72 Topical ........................ 152, 178, 326, 333 Toxic ...... 67, 87, 89, 153, 174, 261, 271, 313, 314, 316, 330, 333 Toxicity................................................ 150 Toxin ............................. 89, 167, 332, 333 Transcutaneous .................................. 240 Translating .......................................... 296 Transplantation ...... 15, 37, 50, 51, 94, 97, 163, 286 Tuberculosis.................. 49, 169, 210, 323 Tyramine ............................................. 166 V Valves ................................................... 69 Vein........................................... 16, 71, 88 Ventilation ... 36, 39, 78, 79, 176, 243, 319 Viral..................................... 169, 219, 320 Virulence ............................... 71, 153, 333 Viscosity................................ 94, 116, 148 W Wheezing ...................................... 12, 190 Withdrawal .......................................... 171