Primary Pulmonary Hypertension - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

PRIMARY

PULMONARY HYPERTENSION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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

ii

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Primary Pulmonary Hypertension: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84561-1 1. Primary Pulmonary Hypertension-Popular works. I. Title.

iii

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

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

iv

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on primary pulmonary hypertension. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

vi

About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON PRIMARY PULMONARY HYPERTENSION .................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Primary Pulmonary Hypertension ............................................... 5 E-Journals: PubMed Central ....................................................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 27 CHAPTER 2. NUTRITION AND PRIMARY PULMONARY HYPERTENSION ........................................ 73 Overview...................................................................................................................................... 73 Finding Nutrition Studies on Primary Pulmonary Hypertension.............................................. 73 Federal Resources on Nutrition ................................................................................................... 76 Additional Web Resources ........................................................................................................... 76 CHAPTER 3. CLINICAL TRIALS AND PRIMARY PULMONARY HYPERTENSION ............................... 77 Overview...................................................................................................................................... 77 Recent Trials on Primary Pulmonary Hypertension................................................................... 77 Keeping Current on Clinical Trials ............................................................................................. 78 CHAPTER 4. PATENTS ON PRIMARY PULMONARY HYPERTENSION ............................................... 81 Overview...................................................................................................................................... 81 Patent Applications on Primary Pulmonary Hypertension ........................................................ 81 Keeping Current .......................................................................................................................... 84 CHAPTER 5. PERIODICALS AND NEWS ON PRIMARY PULMONARY HYPERTENSION ..................... 87 Overview...................................................................................................................................... 87 News Services and Press Releases................................................................................................ 87 Academic Periodicals covering Primary Pulmonary Hypertension ............................................ 90 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 91 Overview...................................................................................................................................... 91 U.S. Pharmacopeia....................................................................................................................... 91 Commercial Databases ................................................................................................................. 93 Researching Orphan Drugs ......................................................................................................... 93 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 97 Overview...................................................................................................................................... 97 NIH Guidelines............................................................................................................................ 97 NIH Databases............................................................................................................................. 99 Other Commercial Databases..................................................................................................... 101 APPENDIX B. PATIENT RESOURCES ............................................................................................... 103 Overview.................................................................................................................................... 103 Patient Guideline Sources.......................................................................................................... 103 Finding Associations.................................................................................................................. 106 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 109 Overview.................................................................................................................................... 109 Preparation................................................................................................................................. 109 Finding a Local Medical Library................................................................................................ 109 Medical Libraries in the U.S. and Canada ................................................................................. 109 ONLINE GLOSSARIES................................................................................................................ 115 Online Dictionary Directories ................................................................................................... 118 PRIMARY PULMONARY HYPERTENSION DICTIONARY .............................................. 119 INDEX .............................................................................................................................................. 163

1

FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with primary pulmonary hypertension is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about primary pulmonary hypertension, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to primary pulmonary hypertension, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on primary pulmonary hypertension. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to primary pulmonary hypertension, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on primary pulmonary hypertension. The Editors

1

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

3

CHAPTER 1. STUDIES HYPERTENSION

ON

PRIMARY

PULMONARY

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and primary pulmonary hypertension, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “primary pulmonary hypertension” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Glaxo Wellcome Drug Proves Helpful in Treating Ailment Linked to Diet Pill Source: Wall Street Journal. Section B, p. 4. January 29, 1998. Summary: The drug company Glaxo Wellcome has announced research findings indicating that prostacyclin, a drug under development by the company is effective in the treatment of primary pulmonary hypertension (PPH). The researchers indicated that patients who developed PPH after taking Redux? (dexfenfluramine) or Pondimin? (fenfluramine) improved with a course of prostacyclin.

4

•

Primary Pulmonary Hypertension

Long-Term Pharmacotherapy in the Management of Obesity Source: JAMA. Journal of the American Medical Association. 276(23): 1907-1915. December 18, 1996. Summary: This article discusses the rationale for the long term use of medications in the management of obesity and reviews currently available scientific studies on the safety and efficacy of pharmacotherapeutic agents. Data sources for the article were original reports and reviews obtained through electronic database searches on anorexiant drugs, supplemented by a manual search of bibliographies. Data synthesis reveals that the long term use of medications to manage obesity was consistent with the current consensus that obesity responds poorly to short term interventions. Net weight loss attributable to medication was modest, ranging from 2 to 10 kilograms. Response to treatment was variable, and those who took the active drug were more likely than those who took placebo to achieve a clinically significant weight loss. Weight loss tended to reach a plateau by 6 months. Although weight remained below baseline throughout treatment, some studies show partial weight regain despite continued drug therapy. Areas of concern relating to long term treatment of obesity with pharmacological agents include the potential for abuse or dependence, the development of tolerance, avoidance of responsibility by patients for their condition, and adverse effects (most of which are mild and self-limited). However, people using anorexiant drugs may experience depression, neurotoxic effects, and primary pulmonary hypertension. The article provides guidelines on selecting appropriate patients for drug treatment of obesity. It concludes that, although there is little justification for the short term use of anorexiant drugs, pharmacotherapy combined with appropriate behavioral approaches to change diet and physical activity helps some obese patients lose weight and maintain the loss for at least a year. 1 table. 117 references. (AA-M).

•

Nifedipine-Induced Gingival Hyperplasia: Non-Surgical Management of a Patient Source: SCD. Special Care in Dentistry. 19(1): 29-34. January-February 1999. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824. Summary: This article reports on a patient who had extensive gingival hyperplasia (overgrowth of the gums) as a response to taking nifedipine (Adalat) for idiopathic pulmonary hypertension. The case history also describes the challenges faced by the oral health practitioner to develop an appropriate regimen of treatment for a patient in whom neither withdrawal of the drug nor substituting for it was feasible, and periodontal surgery was contraindicated. The 19 year old male patient was referred to the authors' clinic for evaluation and treatment of severe gingival hyperplasia, which had developed during the preceding 16 months. The patient had asthma and had been taking theophylline for approximately 5 years; in addition, he had been taking acetylsalicylic acid and nifedipine for primary pulmonary hypertension. He denied any liver disease and had no known immune systemic diseases. The authors describe the treatment regimen that was formulated to reduce the severity of the periodontal problem and to maintain periodontal health. In such medically compromised patients, long term maintenance involves aggressive plaque control, frequent recalls, oral prophylaxis, and deep root planing. 4 figures. 2 tables. 24 references.

•

Appetite Suppressant Agents: Current Problems and Controversies Source: Clinical Diabetes. 15(6): 229-234. November-December 1997.

Studies

5

Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article provides information about appetite suppressant agents. The author notes that obesity is a major contributor to the development of insulin resistance, type 2 diabetes, hypertension, lipid disorders, and coronary heart disease. Topics include central and general obesity; adipose tissue mass regulation; treatment of obesity; noradrenergic agents and serotonergic agents; benefits of weight loss on comorbid conditions; complications of appetite suppressant drug treatment; primary pulmonary hypertension; valvular heart disease; brain serotonin neurotoxicity; and a future perspective. The author concludes that the emergence of severe complications associated with serotonergic appetite-suppressant drug treatment of obesity should not prevent further research. Combination treatment of fluoxetine and noradrenergic agents, for example, is an area of potentially useful clinical investigation. 1 figure. 3 tables. 36 references. (AA-M).

Federally Funded Research on Primary Pulmonary Hypertension The U.S. Government supports a variety of research studies relating to primary pulmonary hypertension. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to primary pulmonary hypertension. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore primary pulmonary hypertension. The following is typical of the type of information found when searching the CRISP database for primary pulmonary hypertension: •

Project Title: AC6 AS THERAPY FOR PRIMARY PULMONARY HYPERTENSION Principal Investigator & Institution: Patel, Hemal H.; Pharmacology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Pulmonary hypertension (PH) is a disease manifest by increased vascular resistance and pressure in the lungs. The prognosis is poor in that patients untreated for PH often develop heart failure leading to death. The only FDAapproved therapy for PH, infused prostacyclin, is cost prohibitive and cumbersome because an infusion pump has to be implanted. This effort produces only symptomatic relief with no therapy for the underlying cause. I aim to use adenoviral delivery of adenylyl cyclase type 6 (AC6), an enzyme that generates the second messenger, cAMP, and is the target of key receptors activated to maintain vascular tone, to pulmonary

2

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

6

Primary Pulmonary Hypertension

artery smooth muscle cells (PASMC) from patients with and without primary PH to determine the benefit and understand the impact of increased AC expression on vascular cell physiology. I hypothesize that enhanced cAMP production via increased expression of AC6 will regulate ion channel function and restore ion homeostasis in diseased PASMC. I also hypothesize that signaling via G proteins is compartmentalized such that "signaling molecular machines" exist to impart the differentiated state of pulmonary vascular smooth muscle. Understanding this higher order organization may help define new approaches to achieve the desired therapeutic end point of reduced vascular tone through viral mediated delivery of effector genes such as AC6. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACE HYPERTENSION

INHIBITION

IN

SINGLE

VENTRICLE/PULMON.

Principal Investigator & Institution: Gersony, Welton M.; Pediatrics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 05-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) The overall goal of this application is to examine treatment modalities which may improve the clinical care of two groups of patients with congenital heart disease: infants born with a single ventricle supplying blood flow to the lungs and body and children with pulmonary hypertension associated with congenital heart disease. The primary hypothesis in infants with single ventricle is that chronic angiotensin converting enzyme (ACE) inhibition favorably modifies the ventricular remodeling response to volume overload and improves ventricular function over the first year of life. Serial changes in ventricular geometry will be assessed using magnetic resonance imaging and compared with measurements of systolic and diastolic function, including the pressure/volume relation and the Tei index, and clinical outcome measures including post-operative course and changes in the Ross? heart failure classification. The beneficial effect of ACE inhibition is expected to occur prior to and following volume unloading surgery with the bidirectional Glenn shunt or hemi-Fontan. The primary hypothesis of the study in congenital heart disease associated with pulmonary hypertension is that the effect of long-term treatment with an oral prostacyclin analogue or an oral endothelin receptor blocker has a salutory effect on exercise capacity, longevity, and quality of life. It will also be determined whether any of these patients carry a defect of the primary pulmonary hypertension-1 gene. Each of these studies could potentially lead to a significant improvement in prognosis: in the single ventricle group by preventing a long-term deterioration in ventricular function and in the pulmonary hypertension patients by improving quality of life and survival without transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGY OF MONOCROTALINE INDUCED PULMONARY HYPERTENSION Principal Investigator & Institution: Segall, Henry J.; Vet Molecular Biosciences; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-MAR-2006 Summary: Monocrotaline (MCT) induced pulmonary hypertension remains a principle model for the biology and development of intervention strategies for the human disease. Current concepts of pulmonary hypertension (PH) assign a primary pathogenetic role to the pulmonary endothelial cell in both human PH and that induced by MCT. Recently, a

Studies

7

genetic lesion in the Bone Morphogenic Protein Receptor (BMPR) has been identified in humans with pulmonary hypertension The overall objective of this grant is to characterize the effects of MCT on the biology of the pulmonary endothelial cell and relate them to the initiating mechanisms of PH. Our previous work has demonstrated that several proteins with potential functional significance for endothelial cells have selective covalent interactions with the reactive intermediate of MCT metabolism, monocrotaline pyrrole (MCTP). This leads to our hypothesis that protein targets of MCT initiate vascular remodeling by altering endothelial cell function similar to endothelial dysfunction in persons with genetic susceptibility to primary pulmonary hypertension. Our specific aims are to further characterize the protein targets of MCT, to determine the functional significance of protein binding in endothelial cells, to evaluate proteins regulating endothelial cell barrier function as potential MCT targets and to determine whether the MCT model alters the BMPR signal pathway affected in humans with PH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLOOD VESSEL FORMATION IN VERTEBRATE DEVELOPMENT Principal Investigator & Institution: Castellot, John J.; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002 Summary: The formation of blood vessels during vertebrate embryogenesis is required for normal development of the organism. Eelucidating the mechanisms regulating the proliferation and differentiation of EC and SMC the cell types which comprise both capillaries and larger vessels is crucial to understanding vascular morphogenesis. Cell number in tissues a governed by the balance between proliferation and programmed cell death (apoptosis). Many external signals have been shown to influence EC apoptosis, including inducers like tumor necrosis factor-alpha and inhibitor like vascular endothelial growth factor (VEGF). The intracellular signaling pathways involved in apoptosis have come under close scrutiny recently; in particular, activation of the Akt family of kinases has been strongly implicated protecting neuronal and fibroblast cells against apoptosis. However, no information is presently available on the role of Art kinases in EC. Based on the preliminary data which demonstrates the presence of Art kinases in EC and the upregulation of Akt kinase activity by VEGF, it is hypothesized that the apoptosis- protective effect of VEGF and other mitogens/survival factors on EC is due to activation of Akt. Specific Aim 1 examines this hypothesis by a) using localizing antibodies to determine the spatial and temporal pattern of Akt expression in the developing mouse; b) measuring Akt kinase kinase activity in cultured EC exposed to apogenic stimuli, apoptosis- protectors, and combinations of the two; and c) forced expression, dominant-negative, and antisense oligonucleotide approaches to assess the functional role of Akt in cultured EC. Vascular morphogenesis (remodeling) also requires careful control of SMC proliferation. Based on work in the PI's laboratory and by others suggesting that heparan sulfates (including heparin) may be physiologic regulators of SMC proliferation in neonates and adults, it is hypothesized that these glycosaminoglycans are important in vascular morphogenesis. A corollary to this hypothesis is that SMC deficient in their response to heparin will display problems in arterial wall development. This appears to be the case in primary pulmonary hypertension of the newborn (one of the most common cardiovascular defects in human neonates), and in the Spontaneously Hypertensive Rat, a well-characterized model system for hypertension. Specific Aim 2 examines this hypothesis by a) assessing the heparin-responsive phenotypes of embryonic and neonatal SMC; b) using in situ hybridization and localizing antibodies to heparin-induced CCN- like protein (HICP), a

8

Primary Pulmonary Hypertension

molecular marker for the heparin-responsive phenotype, to ascertain when and where in development the heparin- responsive phenotype appears; and c) examining the functional role of HICP in knock-out mice. The experiments proposed in these two aims should provide novel and important information about the cellular and molecular mechanisms that regulate formation of the vascular system in development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BMPR2 HYPERTENSION

AND

THE

PATHOGENESIS

OF

PULMONARY

Principal Investigator & Institution: Bloch, Kenneth D.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Primary pulmonary hypertension (PPH) is a disease characterized by elevated pulmonary artery blood pressure, remodeling of the lung vasculature, and progressive right ventricular hypertrophy. Despite recent therapeutic advances, nearly 40% of PPH patients die within three years of diagnosis. The familial form of PPH is inherited as an autosomal dominant trait with incomplete penetrance and has been associated with mutations in the gene encoding the type II bone morphogenetic protein receptor (BMPR2). Moreover, about 25% of patients with sporadic PPH also have BMPR2 mutations. The principal investigator has assembled a multidisciplinary team of scientists with the objective of elucidating the role of BMPR2 in the pathogenesis of PPH. The investigators have already developed a series of genetically modified mice with mutations in the BMPR2 gene, as well as mice with a conditional BMPR2 mutation. BMPR2 mice were found to be normal at baseline but develop greater pulmonary hypertension than wild type mice after prolonged hypoxia. The proposed research is divided into four aims. First, the pulmonary vascular remodeling response to environmental and pharmacologic stimuli associated with the development of pulmonary hypertension in animal models will be compared in wild type and BMPR2 mice. Second, pulmonary vascular endothelial and smooth muscle cells will be isolated from genetically modified mice, and the ability of BMP to modulate cell proliferation, migration, and apoptosis will be assessed. Third, pulmonary vascular structure and function will be evaluated in mice with BMPR2 mutations that retain kinase activity. Finally, mice with a conditional BMPR2 mutation will be used to investigate the contribution of endothelial and smooth muscle cells to the pathogenesis of pulmonary hypertension. The results of the proposed studies will likely provide important insights into the pathogenesis of PPH including why only some patients with BMPR2 mutations develop the disease. Moreover, these studies may validate BMPR2 mice as a valuable model with which to screen new and old drugs with the goal of identifying agents that may cause PPH in individuals predisposed to the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR MECHANISMS OF PPH--ROLE OF POTASSIUM CHANNELS Principal Investigator & Institution: Yuan, Jason X.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 15-JUL-1999; Project End 30-JUN-2003 Summary: Primary pulmonary hypertension (PPH) is a fatal disease in which increased pulmonary arterial pressure and vascular resistance lead to right heart failure and death. The cellular mechanisms of PPH remain unclear, the common contention is that

Studies

9

the disease may have a variety of different etiological triggers. Vasoconstriction and vascular remodeling both contribute to produce increased pulmonary vascular resistance. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a trigger for vasoconstriction and a stimulus for cell proliferation (that leads to media hypertrophy and vascular remodeling). [Ca2+]cyt is regulated by membrane potential (Em) because of the voltage-dependence of Ca2+ channels. Em is partially determined by K+ channel activity. Inhibition of K+ channels depolarizes PASMC, opens voltage-dependent Ca2+ channels, and increases [Ca2+]cyt. We recently observed that the mRNA expression of voltage-gated K+ (Kv) channels and the currents through Kv channels (IK(V)) were both significantly attenuated in PASMC from PPH patients, compared with PASMC from normal subjects (organ donors) and patients with non-pulmonary hypertension diseases (NPH) and secondary pulmonary hypertension (SPH). Furthermore, PPH-PASMC had more depolarized Em and higher [Ca2+]cyt than SPH-PASMC. Based on these data, we hypothesize that: PPH originates, in part, from an abnormality in function and expression of Kv channel(s). The resultant decrease of K+ channel activity leads to Em depolarization, [Ca2+]cyt elevation, and thus excessive pulmonary vasoconstriction and persistent PASMC proliferation. Prostacyclin (PGI2) and nitric oxide (NO) exert their vasodilator effects, in part, by stimulating K+ channel transcription, increasing K+ channel activity, and decreasing [Ca2+]cyt. Four Specific Aims are addressed to test the hypotheses: 1) to characterize IK(V), and to identify the Kv channels that contribute to native IK(V) and are responsible for regulating Em and [Ca2+]cyt in normal PASMC; 2) to compare IK(V), and to determine the qualitative and quantitative differences of Kv channel expression, in PASMC from normal subjects and patients with NPH, SPH and PPH; 3) to characterize and compare the temporal and spatial regulation of [Ca2+]cyt in PASMC from normal subjects and patients with NPH, SPH and PPH; and 4) to investigate the effects of PGI2 and NO on function and expression of K+ channels, and regulation of Em and [Ca2+]cyt. Although SPH and PPH share many clinical characteristics, their etiological mechanisms may be disparate. To search for the defects that are unique to PPH, we will focus on comparing function and expression of Kv channels, and regulation of Em and [Ca2+]cyt between SPH- and PPH-PASMC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLONING OF FAMILIAL PRIMARY PULMONARY HYPERTENSION GENE Principal Investigator & Institution: Nichols, William C.; Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: Primary pulmonary hypertension (PPH) is characterized by elevated pulmonary artery pressures in the absence of a secondary cause. Endovascular occlusion in the smallest pulmonary arteries occurs by proliferation of cells and matrix, with thrombus and vasospasm. Because the initial symptoms of fatigue and dyspnea on exertion are non-specific, diagnosis can often by delayed. Definitive diagnosis requires invasive procedures. The average life expectancy after diagnosis is 2 to 3 years with death usually due to progressive right heart failure. The etiology of the disease remains unknown. Although most cases appear to be sporadic, approximately 6% of cases exhibit an autosomal dominant mode of inheritance with reduced penetrance. The aim of this proposal is to identify the gene(s) responsible for the familial form of the disorder. Following a genome-wide search using DNA samples from affected individuals in six families, evidence for linkage was obtained on chromosome 2q. The

10

Primary Pulmonary Hypertension

maximum two-point LOD score obtained was 6.97, and multipoint linkage analysis yielded a maximum LOD score of 7.86. Haplotype analysis established a minimum candidate interval of approximately 25 cM, and no significant evidence for any of these six families being unlinked to this chromosomal region was observed. Additional families will be genotyped for markers in the candidate region to narrow the interval and help identify potential candidate genes. A physical map of the minimum candidate interval will be constructed, and yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAC) contigs will be assembled. Additional polymorphic markers will be identified in the YAC and Bac contigs more precisely map the critical recombinants defining the minimum interval. Once the smallest interval containing the familial PPH gene has been determined, candidate transcripts will be identified using both available transcript maps as well as exon-trapping methods and analyzed for tissue expression patterns. Leading candidate genes will be evaluated for DNA sequence differences between affected and normal individuals. Identification of the familial PPH gene will enable DNA diagnosis in the families and could potentially allow for the development of novel therapeutics for treatment of both the familial form as well as the more common sporadic form of this life threatening disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS HYPERTENSION

OF

BMPRII

MUTATIONS

IN

PULMONARY

Principal Investigator & Institution: Rodman, David M.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Primary pulmonary hypertension (PPH) is a potentially lethal disorder characterized by pulmonary vasoconstriction and vascular remodeling involving abnormal proliferation of fibroblasts, smooth muscle and endothelial cells. In the year 2000, mutations in the type 2 bone morphogenic protein receptor (BMPR2) were identified as the genetic basis for familial PPH and about 30% of sporadic PPH. BMP signaling had not previously been connected to pulmonary hypertension, and the mechanistic linkage is unknown. We hypothesize that in normal individuals the BMP pathway acts to down-regulate both inflammatory cytokinemediated positive feedback loops and vascular smooth muscle cell proliferation. Insufficient BMP pathway activity in individuals with BMPR2 mutations leads to insufficient damping of these auto-regulatory loops, resulting in the PPH phenotype. We provide preliminary evidence in cell culture systems supporting this hypothesis and have constructed a unique series of transgenic mice to further test the hypothesis. These mice express a human dominant-negative BMPR2 (dnBMPR2) using the tetracycline gene switch system, allowing both spatial and temporal control of expression. We have successfully bred smooth muscle cell and epithelial cell specific dnBMPR2 expressing mice, and are constructing endothelial cell specific mice at this time. Using our in vitro and transgenic models we will test the following three specific aims: 1: Test the hypothesis that the BMP pathway is a negative modulator of the cytokine interleukin-6 (IL-6) in PA SMC, leading to reduced IL-6-mediated signaling and proliferation. 2: Test the hypothesis that loss of PA SMC BMPR2 function in SM22-dnBMPR2 transgenic mice leads to an exaggerated pulmonary hypertensive response in vivo. 3: Test the hypothesis that loss of BMPR2 function in lung cell types other than SMC also contributes to the development of pulmonary hypertension. Upon completion of our studies, we will have tested the hypothesis that the link between BMP signaling and pulmonary hypertension

Studies

11

involves both regulation of the critical cytokine, IL-6, as well as modulation of smooth muscle cell proliferation. We will have also tested the role of four pulmonary cell types, smooth muscle, endothelium, airway epithelium and macrophages in the link between BMPR2 and pulmonary hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTHELIAL CELL GROWTH AND MATURATION IN A 3D CULTURE Principal Investigator & Institution: Cool, Carlyne D.; Pathology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: Research: Structural alterations of the pulmonary arteries in primary pulmonary hypertension (PPH) are characterized by medial muscular thickening and complex vascular lesions known as plexiform lesions. Three-dimensional computerized reconstruction of plexiform lesions from PPH and secondary pulmonary hypertension (PH) patients using endothelial cell (EC) specific markers, shows that the pulmonary ECs of plexiform lesions are in different developmental stages and that their proliferation markedly impedes pulmonary blood flow. The overall goal of this proposal is to examine the effects of shear stress and angiogenic regulators on EC growth and function-as a means to understand the pathogenesis of PH associated with plexiform lesions. We hypothesize that shear stress causes increased VEGF and/or VEGF receptor expression, leading to endothelial cell dysfunction and proliferation. Since Angiopoietin (Ang)1, Ang2, and VEGF cause progressive maturation and organization of ECs lining blood vessel lumina, we also hypothesize that the angiogenic ligands (VEGF, Ang1, Ang2) interact with each other and their tyrosine kinase receptors to maintain an embryonic vasculogenic phenotypic growth. To study the mechanistic questions related to the role of ECs in the genesis of plexiform lesions in PPH, we will use a threedimensional, microvascular EC culture system for systematic studies of angiogenesis in vitro. Preliminary work with the chronic flow system demonstrates a morphologic similarity between the shear-stressed, three-dimensional, in vitro ECs and shear stress conditions will be analyzed with the use of recombinant growth factors or inhibitors of the tyrosine kinase regulation, proliferation, and growth in non-PPG conditions, such as tumor angiogenesis, wound repair and healing , female reproduction, and diabetic retinopathy. Candidate and Environment: Formal mentorship in the lab of Dr. Rubin Tuder will continue throughout the time of this proposal. During this proposal period, I will acquire the independence in though and investigative methods required for the transitions to independent status as a funded researcher, with interest and expertise in the area of experimental pulmonary pathology. An Advisory Committee has been established to aid my academic career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GENE TRANSFER OF ADENYLYL CYCLASE TO PULMONARY SMOOTH MUSCLE CELLS Principal Investigator & Institution: Insel, Paul A.; Professor of Pharmacology and Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: The overriding of this hypothesis is that gene transfer of isoforms of adenylyl cyclase (CA) can be used to increase cyclic AMP (cAMP) synthesis and action in

12

Primary Pulmonary Hypertension

pulmonary artery smooth muscle cells (PASMC). PASMC, whose function is altered in a variety of important clinical conditions associated with pulmonary arterial hypertension, will be used with adenoviral or other viral vectors to assess gene transfer of AC type 6 and 8, two AC isoforms with unique patterns of regulation. We will assess impact o increased AC expression on cAMP generation and on "downstream" responses including activation of cAMP-dependent protein kinase, metabolic, contractile and growth responses, and on ion channel activity and expression. Other studies will assess compartmentation of AC expression and function of PASMC cells derived from patients with primary pulmonary hypertension. Taken together, the proposed studies should provide new information regarding gene transfer of AC to PASMC and impact of increased AC expression of PASMC function. Successful completion of these studies would provide an experimental basis to initiate clinical studies in patients with abnormal PASMC function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC AND ENVIRONMENTAL PATHOGENESIS OF PPH Principal Investigator & Institution: Loyd, James E.; Associate Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Primary pulmonary hypertension (PPH) is a progressive, fatal disease, which threatens the lives of thousands of patients across all age groups. In a recent important advance, mutations in bone morphogenetic protein receptor 2 (BMPR2) have been associated with both familial and sporadic PPH. Our hypothesis is that other genes and biologic events participate in the development of familial PPH, because only 20% of persons with a BMPR2 mutation ever develop PPH. Our target goals are to identify the modifying genes and environmental features that regulate the clinical expression of mutations in BMPR2; to develop understanding about how BMPR2 mutations result in disease; and to identify the undiscovered mutations which cause PPH. The program forms a structural basis to enhance existing collaborations among experienced investigators from six disciplines to optimize progress in the study of PPH. The program will utilize the unique resources of our database and specimen bank developed from 116 PPH families across the US. In families with mutations not yet identified, we will search for alterations in the BMPR2 gene, including promoter and intronic regions, and search for chance recombination events which could confirm another locus near 2q33. Experimental approaches for identifying modifier genes will include genome wide single nucleotide polymorphism and microsatellite scans in large families with known mutations, examination of mitochondrial DNA haplotypes and candidate genes as modifiers, including NOS-1, NOS-3, and the serotonin transporter. We will study the perceived risks and benefits of genetic testing and counseling in many individuals in families at high risk for PPH. We will also identify genetic modifiers of BMPR2 in mouse models of pulmonary hypertension. We will determine the functional mechanisms by which variations found in the BMPR2 alleles alter BMP signal transduction by defining the biochemical effects of the mutant proteins on signaling pathways. The proposal emphasizes that the common themes, complementary expertise and unique technologies assembled into a coordinated program will be more creative, more productive and more likely to advance understanding of the molecular pathogenesis of PPH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

13

Project Title: GENETIC ASPECTS OF PULMONARY HYPERTENSION Principal Investigator & Institution: Morse, Jane H.; Associate Professor of Medicine; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2004; Project Start 23-AUG-1999; Project End 30-NOV-2007 Summary: (provided by applicant): The pathogenesis of primary pulmonary arterial hypertension (PAH) is unknown. The main goal of this project continues to be the identification of genes that cause PAH and how these genes contribute to the pathophysiology of the disease and its clinical subsets. The familial form of primary pulmonary hypertension (FPPH), inherited as an autosomal dominant disease with incomplete penetrance, was known to have a gene, PPH1 located on chromosome 2q32,33. After narrowing this large locus, our studies found mutations of bone morphogenetic protein receptor 2 (BMPR2) caused disease in 9 of 21 FPPH families. Others found BMPR2 mutations in 26% of sporadic PPH. BMPR2 mutations were also found 9% of fenfluramine appetite-associated PAH whereas no mutations were found in PAH patients with HIV-infection or with scleroderma spectrum of disease. BMPR2 mutations remain to be determined in large PAH cohorts of children and adults with anatomically large congenital pulmonary to systemic communications and with sporadic PPH. Our clinical resources include 100 FPPH families and 5 hereditary hemorrhagic telangiectasia (HHT1) families, four have mutations in activin-like receptor 1 (ALK-1), another gene associated with PPH. The identification of BMPR2 gene, a member of the TGF-B superfamly has focused the BMP/TGF-B signaling pathway for new explorations into the pathogenesis of PPH. Our newer aims will investigate the mechanism by which BMPR2 mutations cause disease, identify genetic mutations that cause disease in the 50% of FPPH cases that do not contain mutations in the exons of BMPR2, and identify DNA variations that alter the penetrance of BMPR2 mutations. We are most interested in the long C-terminal tail of BMPR2, which is unique in the TGF-B superfamily. Hopefully, these aims and the large available clinical material should provide pathophysiological information on the functional relevance of BMPR2 mutations, provide an in vitro method of BMPR2 evaluation, and provide the identification of additional risk factors and genes required for disease penetrance. Longitudinal follow of the FPPH and sporadic cases and of the HHT families should give information on the natural history of disease. The results could also define further avenues for therapeutic interventions and potentially provide in vitro models for drug testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HIV TAT EFFECT ON ENDOTHELIAL CELL FUNCTION Principal Investigator & Institution: Terada, Lance S.; Professor of Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2003 Summary: Infection of patients with Human Immunodeficiency Virus 1 (HIV) is associated with diverse alterations in endothelial function. These include syndromes marked by inappropriate endothelial cell (EC hyperplasia (primary pulmonary hypertension), incomplete differentiation (Kaposi's sarcoma), and acute inflammation (pneumonitis, myocarditis, encephalitis, pericarditis). Although these perturbations in EC function can be diffuse, direct infection of EC by HIV is unusual, may be restricted to certain vascular beds, and is generally abortive. Such endothelial alterations are therefore more likely to be the result of HIV-related circulating mediators, rather than of direct endothelial infection by retrovirus. We hypothesize that the secreted HIV

14

Primary Pulmonary Hypertension

transcription factor Tat acts to modify EC proliferation, differentiation, apoptosis, and expression of inflammatory molecules, and additionally, that these effects are modulated by the cytokines TNF alpha, IL-1 beta, and IFN gamma. We further hypothesize that the diverse and sometimes opposing effects of Tat are mediated by the oxidant-dependent differential activation of the various MAP Kinase signaling cassettes. Our preliminary data confirm that exposure of human EC to Tat acutely increases intracellular oxidant levels concomitant with activation of c-Jun amino terminal kinase (JNK). Further, Tat alters the TNF-alpha- mediated activation of JNK and the DNAbinding affinity of the transcription factor AP-1, a potential target of JNK. Our general objectives are to correlate oxidase assembly, oxidant production, MAPK activation, and DNA binding and promoter activation of transcription factors, with cell phenotype (proliferation, differentiation, apoptosis, inflammatory molecule expression, and leukocyte adhesion) in human EC exposed to Tat and cytokines, using a variety of interventions designed to dissect different signaling pathways. The significance of this work is to provide further insight into the cause of various AIDS-related vascular syndromes, as well as to understand the basis for fundamental EC functions in normal individuals. This may lead to specific treatments for HIV-infected patients, and may also suggest novel strategies for treatment of non-HIV related diseases through modulation of endothelial cell function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVED PLASMID/LIPOSOME ADMINISTRATION TO THE LUNGS Principal Investigator & Institution: Sanders, Jonathan R.; Generx+, Inc. 3200 West End Ave, Ste 500 Nashville, Tn 372011322 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-DEC-2003 Summary: (provided by applicant): A major impediment to the successful use of aerosol gene therapy for the treatment of lung diseases is the lack of an efficient and safe aerosol delivery strategy. When the transgene vector is a cationic liposome/plasmid DNA complex, factors that must be considered in designing the optimal aerosol device are the intrinsic instability of the liposome/plasmid complex, physical disruption of the complex upon aerosolization, and maximizing the amount of the complex deposited in the lung while minimizing contamination of the environment with exhaled transgene vector. Under support of a Phase I SBIR, we have systematically evaluated how physical stability and the process of aerosolization affects transfection efficacy in airway cells in vitro. These data have permitted us to design a liposome/plasmid DNA aerosolization device for use in humans with pulmonary and pulmonary vascular disease, which we believe could deliver potentially therapeutic genes to the airspaces in a highly efficient and safe manner. The purpose of this Phase II application is to develop a prototype plasmid/liposome delivery device to the point that it is testable in humans. Specifically, we propose to use this strategy to deliver the gene encoding the cyclooxygenase (COX) enzyme to the distal airspaces of humans with primary pulmonary hypertension (PPH). In order to achieve this goal, we will quantify pulmonary deposition, distribution, and clearance profiles in normal sheep of aerosols with different particle sizes aiming to maximize distal deposition; test strategies for improving the physical stability of the complex; and using the optimized delivery system, determine the efficacy of delivering the COX gene to distal airspaces in reversing pulmonary hypertension in the sheep model of PPH. PROPOSED COMMERCIAL APPLICATIONS: This project is part of a geneRx+ program to develop aerosol devices to efficiently deliver plasmid DNA/fiposome complexes to the distal airspaces of the human lung in order to treat

Studies

15

both primary and secondary pulmonary hypertension. The partnership between geneRx+ and Profile Therapeutics represents a unique alliance, the goal of which is to develop aerosol devices specifically designed to efficiently nebulize plasmid/liposomes complexes to humans. If our concepts prove correct, then these devices will become the industry benchmark for transgene/liposome aerosol delivery devices. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF APOPTOSIS IN LUNG VASCULAR SMOOTH MUSCLE Principal Investigator & Institution: Suzuki, Yuichiro J.; Assistant Professor; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Primary pulmonary hypertension (PPH) is rare, but often fatal, with increased incidence in users of appetite suppressants. It is characterized by increased lung vascular resistance due to thickening of pulmonary arterial walls. The cellular mechanisms that regulate smooth muscle cell number, however, have not been defined. Lack of such knowledge interferes with the development of new therapeutic strategies that are designed to prevent and/or treat this condition. My long-range goal is to identify the mechanisms for the regulation of apoptosis in human pulmonary artery smooth muscle cells (HPASMC). The objective of this application is to evaluate specifically the role of GATA transcription factors. The central hypothesis of the application is that GATA factors regulate apoptosis and survival. The hypothesis has been formulated on the basis of strong preliminary data, which suggest that i) GATA-4 and -6 are expressed in HPASMC, ii) apoptotic stimuli downregulate the GATA activity, and iii) serotonin and endothelin-1 exert anti-apoptotic signaling and enhance the GATA activity. The rationale for the proposed research is that, once knowledge of the mechanisms that regulate the lung vascular medial thickening has been obtained, it will lead to new strategies that can be used to prevent and/or treat PPH, thereby reducing the morbidity and mortality that are associated with this condition. I am uniquely prepared to undertake the proposed research because my lab has been studying GATA factors, and many of the techniques and reagents are already available. The central hypothesis will be tested and the objective of the application accomplished by pursuing two specific aims: 1) Identify the mechanisms of HPASMC apoptosis induced by nitric oxide and retinoic acid, and 2) Determine the mechanisms by which serotonin and endothelin-1 exert anti-apoptotic signaling. The proposed work is innovative, because it will investigate novel transcription factors in lung using an approach that has been used in the studies of cardiac muscle. It is my expectation that GATA factors are involved in the regulation of apoptosis of HPASMC. These results will be significant because they are expected to provide new agents for preventative and therapeutic interventions of PPH. In addition, it is expected that the results will fundamentally advance the field of lung cell biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MECHANISMS OF DEFORMATION-INDUCED ATP RELEASE FROM RBCS Principal Investigator & Institution: Sprague, Randy S.; Internal Medicine; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-AUG-2000; Project End 31-JUL-2004

16

Primary Pulmonary Hypertension

Summary: When traversing microvascular beds, such as in the lung, red blood cells (RBCs) are subjected to mechanical deformation. Our previous findings that RBCs are required for flow-induced nitric oxide (NO) synthesis in the lung and that mechanical deformation of RBCs results in the release of adenosine triphosphate (ATP), a stimulus for endothelial NO synthesis, suggested a novel mechanism for the control of vascular resistance in the pulmonary circulation. In this construct, as the RBC is increasingly deformed by increments in the velocity of blood flow through a vessel and/or by reductions in vascular caliber, it releases ATP which stimulates the synthesis of NO resulting in relaxation of vascular smooth muscle and, thereby, an increase in vascular caliber. We propose that RBC-derived ATP contributes to the low vascular resistance of the healthy lung. Moreover, if deformation-induced ATP release from RBCs is an important determinant of vascular resistance in the lung, then a signal- transduction pathway for ATP release in response to this stimulus should be present in that cell. Here, we address the hypothesis that mechanical deformation of RBCs sets into motion specific signal transduction pathways which culminate in release of adenosine triphosphate (ATP). In this proposal we intend to 1) demonstrate that heterotrimeric G proteins are components of a signal transduction pathway for deformation-induced release of ATP from RBCs of rabbits and healthy humans, 2) establish that increases in intracellular cAMP are required for deformation- induced ATP release from these RBCs, 3) demonstrate that the activity of protein kinase A (PKA) is required for deformationinduced ATP release from RBCs of rabbits and healthy humans, 4) establish that ATP release from these RBCs requires the activity of the nucleoside transporter and 5) establish that deformation- induced ATP release from RBCs is decreased in humans with primary pulmonary hypertension and determine the associated defect(s) in the signal-transduction pathway for ATP release in these patients. The successful completion of the studies described in this proposal will define a new role for the RBC as a regulator of vascular resistance in the pulmonary circulation and may provide new insights into the pathophysiology of pulmonary hypertension. This hypothesis is the logical extension of our previous work and is consistent with a major focus of this group, namely, identification and characterization of those mechanisms responsible for the control of pulmonary vascular resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROHORMONAL HYPERTENSION

ACTIVATION

IN

PULMONARY

Principal Investigator & Institution: Kawut, Steven; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Candidate's Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient-oriented research related to pulmonary vascular disease. Training will include formal epidemiological course work in clinical research and closely mentored completion of the research protocol. Environment: The Center for Clinical Epidemiology and Biostatistics (CCEB) will provide formal coursework and structured mentoring. The CCEB, Pulmonary Vascular Disease Program, and General Clinical Research Center at the University of Pennsylvania Medical Center will provide research support. Research: Primary pulmonary hypertension (idiopathic) and secondary pulmonary hypertension (associated with portal hypertension, anorectic use, HIV, scleroderma, and other collagen vascular diseases) cause substantial morbidity and mortality. Although there are available therapies and interventions, they may be costly and risky in themselves. In addition, targeting therapy at the mechanism of morbidity

Studies

17

and mortality and distinguishing highrisk patients have been suboptimal. There is evidence that certain vasoactive substances may play an important role in the disease process of pulmonary arterial hypertension. Studies have documented elevated levels of endothelin, natriuretic peptides, and norepinephine in patients with this disease. It is well known that these neurohormones play important mechanistic and predictive roles in left-sided heart failure. Similarly, there is much potential for these neurohormone levels in determining 1) the mechanism of disease and 2) the prognosis in pulmonary arterial hypertension. We propose an investigation of patients with pulmonary arterial hypertension to examine whether levels of these biomarkers at baseline and at six month follow-up are associated with right-sided heart failure and cardiovascular death. We will formulate prediction rules using neurohormone levels and clinical variables to improve prognostication and management in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NITRIC HYPERTENTION

OXIDE/CARBON

MONOXIDE

IN

PULMONARY

Principal Investigator & Institution: Dweik, Raed A.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 10-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): We have shown that patients with primary pulmonary hypertension (PPH) have low levels of nitric oxide (NO), a potent vasodilator, in exhaled breath suggesting a role for NO in the pathophysiology of pulmonary hypertension. The purpose of this proposed research is to determine the mechanism(s) for low NO in PPH. Potential mechanisms that will be addressedin the experiments are inhibition of NO production by CO and enzyme kinetic abnormalities affecting the sensitivity of NO synthase (NOS) to oxygen. We have previously shown that oxygen concentrations in the physiologic range determine the rate of NO synthesis in the lung. However, PPH individuals have low NO despite receiving supplemental oxygen therapy. This suggests that NO synthases in PPH may be less sensitive to oxygen and thus require higher than normal oxygen to produce NO. Furthermore, CO can directly affect endogenous NO synthesis. In preliminary data, CO in PPH is in the range that may lead to inhibition of NOS activity and NO generation. We hypothesize that NO is decreased in PPH perhaps as a consequence of high CO levels and/or impaired NO production in response to oxygen. As an extension of this hypothesis, we also propose that effective therapies such as epoprostenol, may act in part by increasing NO levels in PPH. To test this hypothesis, we propose the following specific aims: Aim 1. Determine the levels of Carbon monoxide (CO) in relationship to NO and severity of disease in PPH. Aim 2. Study the effect of oxygen and epoprostenol on NO levels in PPH in vivo. Aim 3. Study the effect of 02 and CO on NOS expression and activity in vitro. Formal course work and education are incorporated into the training component of this proposal. The candidate will have direction from leaders in the field of lung biology and pulmonary hypertension through a mentoring group. Through the 5 year award, the candidate will develop his skills in (i) hypotheses-driven design of studies, (ii) analyses and interpretation of data, and (iii) writing of manuscripts, abstracts and presenting data at meetings. The training component of this proposal will lead to the candidate's transition to a fully independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

18

•

Primary Pulmonary Hypertension

Project Title: NO SYNTHESIS AND CONSUMPTION IN THE LUNG Principal Investigator & Institution: Erzurum, Serpil C.; Professor; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-MAR-2005 Summary: In designing this proposal equally careful attention has been placed on the research plan and the mentoring component. The research plan is based upon a patientoriented approach to primary pulmonary hypertension (PPH), a fatal disease characterized by progressive increase in pulmonary artery pressure. Our data show that NO and NO reaction products (NOx) are lower in lungs of PPH than health controls. We propose that the low levels of NO and NOx in PPH are due to decreased NO synthesis and increased NO consumption by reactions with oxidant species leading to alternative reaction endproducts. Preliminary studies indicate that NOx are correlated in an inverse relationship to pulmonary artery pressures in PPH. Theoretical modeling and simulation of our data suggest that progression and mortality in PPH is predicted by NOx. These data indicate a role for NO and oxidants in the pathophysiology of PPH. To test our hypothesis that NOx predict progression of PPH, we will obtain longitudinal data on pulmonary artery pressures, cardiac output and lung diffusion capacity in PPH patients, and model these factors as linear functions of the corresponding levels of NOx. To test our hypotheses on mechanisms responsible for low NO levels, NO synthase (NOS) levels and activity will be quantitated and localized in PPH lungs in comparison to controls. Further, oxidative mechanisms of NO consumption will be studied in vivo and in an in vitro cell culture system. The program will allow the candidate to focus intensively on patient-oriented research and expand her mentoring endeavors of beginning clinician investigators. The mentoring component of this proposal includes instruction in molecular biology, analytic techniques, research design, data interpretation, preparation of abstracts, manuscripts, and presentations taught by the candidate, with input from biostatistician, and on a quarterly basis from advisors who are highly successful in patient-oriented research. Since clinical research increasingly utilizes basic investigative techniques, knowledge of basic research is incorporated into the program through formal graduate level coursework. The program will result in the development of physician-scientists that use state-of-the art research techniques for investigation of human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NONINVASIVE ASSESSMENT OF PRIMARY PULMONARY HYPERTENSION Principal Investigator & Institution: Shandas, Robin; Professor; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (Applicant's Abstract): This proposal addresses the problem of evaluating the efficacy of newly developed agents for the treatment of primary pulmonary hypertension. The use of catheter techniques to measure pulmonary vascular resistance severely limits routine evaluation of such treatments. We propose to develop, refine and test a non-invasive ultrasound based means of accurately evaluating pulmonary vascular resistance in children with primary pulmonary hypertension. The hypothesis for this project is based on the relationship between changes in downstream impedance within a fluid system and the characteristics of the pressure pulse propagation wave that develops within the arterial walls. We propose to show that downstream impedance affects the pulse propagation wave traveling within the main pulmonary

Studies

19

artery and that changes in downstream impedance, as would occur with treatments such as inhaled nitric oxide or infused prostaclyin, can be followed by measuring pulse propagation characteristics. Furthermore, we propose that the pressure pulse propagation in the main PA affects local velocities, and that such changes in local velocities can be quantified as a velocity propagation using non-invasive ultrasound color M-mode imaging. This should significantly aid in evaluating new treatments for primary pulmonary hypertension and thereby expand treatment options and improve quality of life for patients. The aims of this project, therefore, are: 1. Demonstrate analytically that a fundamentally rooted mathematical and physical foundation exists for using velocity data to extract pressure pulse propagation characteristics for pediatric primary pulmonary hypertension. 2. Develop and test a method for using color Mmode velocity data to predict downstream impedance using highly reproducible in vitro models. 3. Determine clinical utility of the color M-mode approach using existing clinical protocols studying the efficacy of nitric oxide and/or 100 percent 02 treatment in the catheterization laboratory to reduce pulmonary vascular resistance in children with primary pulmonary hypertension. 4. Determine whether color M-mode measured velocity propagation (Vel-prop) predicts pulmonary vascular resistance in the clinical situation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS HYPERTENSION

OF

FAMILIAL

PRIMARY

PULMONARY

Principal Investigator & Institution: Newman, John H.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PKC VASODILATION

SIGNALING

IN

CAMP-INDUCED

PULMONARY

Principal Investigator & Institution: Barman, Scott A.; Pharmacology and Toxicology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Primary Pulmonary Hypertension (PPH) is a disease of unknown origin that results in narrowing Of the pulmonary vasculature causing high pulmonary blood pressure often leading to heart failure. Currently there is little knowledge on the cellular and molecular foundation of PPH. Normally, signaling mechanisms which elevate cAMP and cGMP in the pulmonary vasculature allow for the maintenance of a low pressure, high perfusion environment. It is well documented that the activation of the large-conductance, calcium-and voltage-activated potassium (BKca) channel is of primary importance in the regulation of pulmonary arterial pressure and inhibition of the BKca channel has been implicated in the development of pulmonary hypertension. Preliminary data from patch-clamp studies in pulmonary arterial smooth muscle cells (PASM) of the fawn-hooded rat (FHR), a recognized animal model of pulmonary hypertension, suggests that cAMP, an activator of cAMP-dependent protein kinase (PKA), opens the BKca channel through "cross-activation" of the cGMPdependent protein kinase (PKG). In contrast, protein kinase C (PKC) which causes pulmonary vasoconstriction, inhibits the BKca channel in FHR PASM, but activates the BKca channel in Sprague-Dawley (control) rats. Therefore, the hypothesis of the

20

Primary Pulmonary Hypertension

proposed studies is that cAMP-dependent vasodilators relax pulmonary arteries by opening BKca channels in pulmonary arterial smooth muscle by stimulating the activity of PKG, an effect inhibited by activation of PKC in FHR. This hypothesis will be tested by employing state-of-the-art techniques of electrophysiology, vascular contraction, and biochemistry/molecular biology to determine: 1) the effect of cAMP-dependent vasodilators on pulmonary arteries in vitro, 2) the effect of cAMP-elevating agents on whole-cell and single channel K+ currents from single myocytes isolated from pulmonary arteries, 3) cAMP-dependent "cross-activation" of PKG, and 4) the role of PKC on BKca channel activity and whether there is a direct interaction between PKG and PKC on BKca channel modulation. The long term goal of the proposed study is to understand how cAMP-elevating agents cause pulmonary arterial vasodilation by an endothelium-independent mechanism. It is believed that these studies will lead to the development of novel therapeutic agents that will help reduce the morbidity and mortality associated with PPH and other pulmonary vascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTACYCLIN SYNTHASE AND PROSTACYCLIN RECEPTOR IN PH Principal Investigator & Institution: Geraci, Mark W.; Director, Gene Array Facility; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant) Severe pulmonary hypertension, including primary pulmonary hypertension (PPH), is an important clinical problem with few clinical treatment options. The chronic, intravenous infusion of prostacyclin (PGI2) has been established as the treatment of choice for patients with PPH. It is now clear that longterm benefits occur which obviate the need for transplant in many cases. The physiological effects of prostacyclin on platelet behavior, vascular tone control, and cell proliferation are well established; however, we do not know whether prostacyclin effects the vascular remodeling in chronic pulmonary hypertension. Our overall hypothesis is that prostacyclin, through membrane-receptor dependent and independent mechanisms, is an important modulator of pulmonary vascular remodeling. We have demonstrated loss of the prostacyclin receptor (PGIR) protein in the smooth muscle cells of precapillary resistance arteries in patients with PPH. We postulate that impairment of the prostacyclin signal transduction contributes to pulmonary vascular remodeling. We have generated transgenic animals with selective pulmonary prostacyclin synthase (PGIS) overexpression. These animals are protected from the development of hypoxic pulmonary hypertension, and show no acute vasoconstriction or chronic vascular remodeling. In contrast, PGIR knockout (KO) mice, in response to hypoxia, develop rapid pulmonary hypertension accompanied by vascular remodeling. Microarray analysis of the lungs from the transgenic animals demonstrates a change in the global pattern of gene expression, which may be responsible for the "protected" phenotype, including changes in PPARs and COX-2. Our underlying concept is that PGI2 exhibits both membrane-receptor mediated and nuclear-receptor-mediated actions. These alternative mechanisms could include direct effects on gene expression, signaling pathways not yet recognized, or changes in the level of other eicosanoids. Our goal is to examine, using both animal models and cell systems, the effects of PGIS and PGIR on vascular smooth muscle cell (VSMO) growth and differentiation. In Specific Aim 1, we will determine whether pulmonary vascular tone and remodeling are mediated through the PGI2 receptor using bitransgenic mice

Studies

21

with PGIS overexpression, but lacking PGIR. Specific Aim 2 is designed to define the effect of PGIS and PGIR on the growth and remodeling of vascular smooth muscle cells. The results of this work are designed to elucidate new potential therapeutic targets for treating pulmonary hypertension, and broaden our understanding of vascular pathology in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PULMONARY VASCULAR TREE DEVELOPMENT, GROWTH & REMODLING Principal Investigator & Institution: Glenny, Robb W.; Associate Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 20-AUG-1997; Project End 30-JUN-2006 Summary: (provided by applicant): The pulmonary vascular tree has a unique design that optimizes the distribution of blood flow for gas exchange. Under normal conditions, its geometry is an end product of fetal development and postnatal growth. In disease, further restructuring occurs through vascular remodeling. Recent advances in molecular and cellular biology provide insights into how these three determinants influence vascular structure at the cellular level. The proposed work integrates physiologic studies with in situ cellular and molecular techniques to determine the functional significance of these factors in the whole living animal. Specific aim 1: Determine the degree of genetic control on pulmonary vascular tree growth during fetal development and how its geometry changes with postnatal growth. We will use armadillos, a unique animal that produces litters of identical offspring. By comparing the spatial distribution of blood flow within and across litters, we can quantify the genetic influence on vascular tree development and regional perfusion. We will also measure regional blood flow in growing pigs to identify patterns of blood flow redistribution. Patterns that are spatially clustered will provide evidence that postnatal growth of the pulmonary vascular tree may be locally regulated. Specific aim 2: Identify triggers of pulmonary vascular remodeling during chronic hypoxia. We will focus on the roles of mechanical wall stresses in promoting cellular proliferation and apoptosis in rat pulmonary arteries. Specific aim 3: Identify triggers of pulmonary vascular remodeling in pulmonary hypertension induced by vascular endothelial growth factor receptor-1 inhibition. We will focus on the roles of mechanical wall stresses in promoting plexiform lesions that are characteristic of primary pulmonary hypertension. The proposed work is designed to determine relationships between function, structure and genetic controls in the pulmonary circulation at the organ level. The most novel and significant aspect of the work is that cellular and molecular mechanisms will be explored in the intact animal. The findings will fill important gaps in our knowledge of pulmonary vascular development and triggers of remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HYPERTENSION

RAFT/CAVEOLAR

MECHANISMS

IN

PULMONARY

Principal Investigator & Institution: Sehgal, Pravin B.; Professor; Cell Biology and Anatomy; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This translational research proposal seeks to apply recent novel insights into the mechanisms of cell signaling at the level of the plasma membrane (the caveola/raft signaling hypothesis and the interleukin-6-raft-STAT3

22

Primary Pulmonary Hypertension

signaling model) to an understanding of the pathogenesis of PH. Caveolin-1-containing detergent-resistant plasma membrane rafts are now recognized as specialized signaling organelles, including cytokine signaling. There is now growing evidence for a role of cytokines in the pathogenesis of lung diseases. As examples, elevated serum levels of IL6 have been observed in primary pulmonary hypertension (PH) and in PH associated with autoimmune diseases and AIDS. In a rat model, a single injection of the plant alkaloid monocrotaline (MCI) results within 48 hrs in endothelial cell damage, membrane leakage, upregulation of IL-6 mRNA and bioactivity but a marked downregulation of caveolin-1 in the lung, followed by development of PH 10-14 days later. The focus of the proposed studies is two-pronged: (a) to evaluate the hypothesis that pulmonary endothelial-cell raft/caveolar disruption by MCT is an initiating event in the pathogenesis of PH (Specific Aim I), and (b) to investigate the function of membrane rafts and of the newly discovered cytosolic caveolin-containing Palade complexes in IL-6-induced STAT3 signaling in lung-specific cells (Specific Aims II and III). Aim I will include investigations of the time-course, histologic location, and cellular and molecular mechanisms for the downregulation of caveolin proteins and gene expression, and of the integrity of caveolar/raft function in pulmonary vascular and parenehymal tissues of MCT-treated rats. Aim II includes molecular studies of the mechanisms of association of STAT3 with caveolin-1 and of STAT3 activation in plasma membrane rafts in pulmonary endothelial cells, alveolar type II-like epithelial cells and lung fibroblasts. Aim Ill includes studies of the protein components of STAT3containing cytosolic Palade complexes and their function in ferrying signaling molecules from the plasma membrane rafts to the cell interior. Mechanistic insights derived from this project are likely to suggest novel therapeutic approaches in the management of pulmonary hypertension. Moreover, the proposed studies are of particularly broad significance in that insights into the molecular mechanisms involved in raft-STAT signaling are likely to be applicable to cytokine-mediated activation of STAT transcription factors in perhaps all cell types, as well as to other signaling pathways localized in raft microdomains (eNOS and angiotensin II signaling). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF HYPOXIA INDUCIBLE FACTOR-1 BY NITRIC OXIDE Principal Investigator & Institution: Palmer, Lisa A.; Assistant Professor; Pediatrics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: Hypoxia inducible factor-1 (HIF-1) is a transcription factor involved in the regulation of genes induced by low levels of oxygen. Regulation of HIF-1 is primarily determined by the stability of the HIF-1alpha subunit. In normoxia, HIF-1alpha mRNA is made but the protein is rapidly degraded by the ubiquitin-proteasome pathway. Nitric oxide (NO) has been shown to induce HIF-1 expression in normoxia. Our preliminary evidence suggests that S-nitrosylation reactions stabilize HIF-1alpha by inhibiting elements of the ubiquitin activating system. Because 1) the pulmonary vascular endothelium is not exposed to the profound levels of hypoxia often required to induce HIF-1 in vitro; 2) hemoglobin deoxygenation is associated with the transfer of nitrogen oxides to the vascular endothelium at pO2s more relevant to intravascular pathophysiology; and 3) downstream effects of HIF-1alpha stabilization on gene expression are implicated in the pathophysiology of pulmonary hypertension, we propose to clarify the mechanism by which NO activates HIF-1alpha in vitro and in vivo by testing the following hypotheses: Hypothesis number 1.: The expression of HIF-1 is

Studies

23

regulated by nitric oxide (NO) in normoxia by S-nitrosylation of protein thiols. Hypothesis number 2. NO modifies HIF-1alpha stability in normoxia by modifying ubiquitin-dependent degradation through S- nitrosylation of HIF-1alpha and one or more enzymes of the ubiquitin activating pathway. Hypothesis number 3. Snitrosoglutathione, and/or other related nitrogen oxides arising from hemoglobin deoxygenation induce HIF-1 expression in vivo. In testing this third hypothesis, we will control the effects of hypoxia on the gamma glutamyl transpeptidase knockout mouse. We have shown that this animal has attenuated responses to deoxyhemoglobin, that appear to involve decreased bioactivation of S-nitrosoglutathione. Taken together, these hypotheses represent a completely novel direction in the study of abnormal gene regulation in the pulmonary vascular endothelium. At the completion of this project, we believe we will have identified several new targets for the prevention and treatment of hypoxia- induced and primary pulmonary hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF KV CHANNELS BY ANOREXIGENS Principal Investigator & Institution: Takimoto, Koichi; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Voltage-gated K+ (Kv) channels in pulmonary arterial smooth muscle cells (PASMCs) have been implicated in the initiation of pulmonary hypertension: inhibition of these channels results in membrane depolarization and an increase in intracellular Ca2+ concentration, leading to vasoconstriction and cell growth/remodeling. The use of anorexic agents (phentermine, fenfluramine and their related drugs) is associated with an increased incidence of pulmonary hypertension. These drugs also decrease the activity and expression of Kv channels in PASMCs. Thus, understanding the mechanisms by which these identified stimuli produce alterations in the function and level of these channels may provide clues for prevention and treatment of primary pulmonary hypertension. The anorexic agents reduce Kv channel activity at multiple steps. They acutely inhibit 4-aminopyridine (4AP)-sensitive Kv current in PASMCs. Furthermore, long-term treatment of PASMCs with fenfluramine leads to decreases in Kv current density and the expression of Kv1.5 mRNA. Lung tissues from patients with primary, but not secondary, pulmonary hypertension also exhibit reduced expression of Kv1.5 mRNA. These findings suggest acute and long-term exposures to these drugs influence 4-AP-sensitive Kv channels at plasma membrane and transcription of Kv channel subunit genes, respectively. Using Xenopus oocyte expression system, we found that fenfluramine and phentermine inhibit Kv1.5, Kv2.1 and Kv4.2, but not Kv3.1b, current. Using cultured rat PASMCs and heterologous expression systems, we have analyzed molecular mechanisms underlying the anorexigen-induced changes in the activity and expression of Kv channels. First, exposure to fenfluramine decreased endogenous Kv2.1 proteins in PASMCs. The drug also reduced heterologously expressed Kv2.1, but not Kv1.5 or Kv4.3, proteins in a mammalian cell line. In addition, the non-selective kinase inhibitor staurosporin mimicked and occluded the fenfluramine-induced decrease in the channel protein level in PASMCs. Second, the anorexic drugs caused significant decreases in the level of endogenous Kv1.5 mRNA and reporter gene expression driven by the Kv1.5 promoter in PASMCs. Reductions in the channel promoter activity were also seen in A7r5 smooth muscle cells, but not in CHO or HEK293 cells. Finally, fenfluramine and phentermine rapidly and reversibly inhibited Kv1.5, Kv2.1 and Kv4.2, but not Kv3.1b, currents in Xenopus oocytes. Thus, the anorexigen-induced pulmonary hypertension may be

24

Primary Pulmonary Hypertension

mediated by their multitude of actions to produce acute and long-term inhibition of PASMC Kv channels. Hence, this proposal is to identify molecular mechanisms for anorexigen-induced inhibition of Kv channels at the three levels: a slow decrease in Kv2.1 proteins, inhibition of Kv1.5 gene transcription and blockade of Kv currents at plasma membrane. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ACE IN PULMONARY HYPERTENSION Principal Investigator & Institution: Schuster, Daniel P.; Associate Dean of Clinical Studies; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2003 Summary: Although angiotensin converting enzyme (ACE) is important for controlling systemic blood pressure and sodium balance, recent evidence also indicates that ACE is important in the local tissue remodeling that accompanies various forms of injury. However, in humans, the potential importance of ACE has largely been inferred from the effects of ACE inhibitors on morbidity and mortality in various clinical trials, and not on direct assessments of tissue ACE expression i significantly increased in remodeling conducting pulmonary arteries in tissue obtained at the time of lung transplantation from patients with primary pulmonary hypertension (PPH). Thus, it is reasonable to hypothesize that ACE may also be important to the vascular remodeling that accompanies pulmonary vascular diseases like PPH. Traditionally, such a hypothesis would be tested in humans with a randomized placebo-controlled trial of an ACE inhibitor. However, supporting animal experimental data is limited to rodent models of the disease, and given the known risks of using vasodilators in PPH patients, the end-point for dosing in humans is also uncertain. Therefore, to be able to evaluate whether it is possible to inhibit lung ACE per se without causing systemic side effects, we have developed a safe, non- invasive, repeatable method to evaluate pulmonary ACE function using the radioactive ligand F-18 fluorocaptopril, and positron emission tomographic (PET) imaging. The method has been successfully implemented in animals and humans. Together with a recently developed large animal model of pulmonary hypertension, we plan to provide the needed evidence to support a clinical trial of the efficacy of ACE inhibition in PPH by meeting the following specific aims: 1) determine whether ACE expression is altered by, and whether ACE inhibition affects the development of, experimentally-induced pulmonary hypertension in a large animal model suitable for PET imaging; 2) determine whether pulmonary ACE expression is altered from normal in humans with PPH; and 3) determine an effective, safe dosing regiment of oral ACE inhibitor that will block at least 75% of lung ACE in vivo in humans with pulmonary hypertension. Not only will these studies help justify clinical trial ACE inhibitors in PPH or similar syndromes, but they will also be directly relevant to the eventual application of PET to studying other pulmonary receptor systems using radioligands developed in other projects of this Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TARGETING ACTIVE ADAPTORS TO CONTROL ENDOTHELIAL DAMAGE Principal Investigator & Institution: Wei, Sheng; Interdisciplinary Oncology Prg; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009

Studies

25

Summary: (provided by applicant): Upon cell-cell contact, one of the mechanisms of immune cells to cause tissue damage is by delivery of lytic granules containing preformed effector molecules--perforin proteins and granzyme proteases. The presence of granzymes and perforin in the extracellular milieu not only reflects the presence of activated CTL and NK cells but also significantly contribute to inflammatory reaction. These protein enzymes can cause circular pore-like lesions on the membrane surface of endothelial cells and induce target cell death leading to local tissue damage and chronic vascular cell damage. Increased granzyme level is closely correlated with the inflammatory activity in autoimmune diseases (e.g. rheumatoid arthritis) and virallyinfected lung and heart diseases. A clear understanding of the pathophysiology of inflammation mediated tissue damage would greatly facilitate management of this disease. The signal transduction pathways in effector lymphocytes, which trigger the redistribution of the lytic granules towards the target endothelial cells, are not well defined. Identification of key signaling molecules which specifically control this lytic process could enable pharmaceutical disruption of this process, thereby reducing the tissue damage mediated by activated lymphocytes. In this proposal, we will use a human primary pulmonary endothelial cell line, CRL- 2598, as the trigger to activate the lytic signal cascade in NK cells. Using biochemical and gene delivery approaches, we will directly test the hypothesis that the early signals via NK activation receptors and their associated adaptor proteins, DAP12 and DAP10, will play a specific role in control of granule movement in NK cells. Blocking of this initial step, at the level of the adaptor proteins, will inhibit granule exocytosis. More importantly, we will test our hypothesis on LGL leukemic patients with primary pulmonary hypertension (PPH) and determine if DAP10 and/or DAP12 critically control NK cell- mediated endothelial cell damage and death. A better understanding of the signaling pathways that control granule movement and exocytosis will offer new opportunities, e.g. design of DAP10 and DAP12 antagonists, for therapeutic intervention to specifically control lymphocytemediated tissue damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THROMBOXANE REGULATION

SYNTHASES-ENZYMOLOGY

AND

GENE

Principal Investigator & Institution: Wang, Lee-Ho; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2004; Project Start 01-JUL-1998; Project End 30-NOV-2007 Summary: (provided by applicant): Thromboxane synthase (TXAS) is a "non-classical" cytochrome P450 that converts prostaglandin H2 to thromboxane A2 (TXA2), a potent inducer of vasoconstriction and platelet aggregation. TXA2 is believed to be a crucial factor contributing to a variety of cardiovascular and pulmonary diseases such as atherosclerosis, myocardial infarction and primary pulmonary hypertension. To understand how the biosynthesis of TXA2 is controlled, it is essential to have an integrated knowledge of TXAS structure/function relationship and its gene regulation. We showed that TXAS shared similar spectral features with other P450s but, unlike other P450s, had a very high turnover number and catalyzed a "peroxidase-like" reaction with a rate-limiting step at the substrate binding. To continue our efforts in understanding this important enzyme, our specific aims are to (1) evaluate the monooxygenase potential of TXAS by determining the redox potential of TXAS heme-iron, characterizing the interaction of TXAS with P450 reductase and investigating the hydroxylase reaction using oxene-donating reagent, (2) determine the structure/function relationship of the active site residues in TXAS catalysis by site-

26

Primary Pulmonary Hypertension

directed mutagenesis and self-inactivation analysis, and (3) solve crystallographic structures of TXAS and its complexes with substrate analog. Regulation of TXAS expression occurs at the transcriptional level. TXAS expression level is cell-type preferential; high in hematopoietic cells and low in non-hematopoietic cells. The binding site for NF-E2 is the most important cis-element for TXAS expression in vivo. The transcription factors p45 NF-E2 and mafG form a heterodimer which activates TXAS transcription in hematopoietic cells. In the non-hematopoietic A549 cells, Nrf2 activated TXAS expression through the NF-E2 site. Thus, TXAS gene utilizes a single cis-acting element but different trans-acting factors to achieve cell-preferential expression. Our results also demonstrated that chromatin structure plays a critical role in TXAS expression. We showed that binding of NF-E2 is associated with the disruption of nucleosomal structure of TXAS promoter. This disruption is likely via CBP/p300. We hypothesize that the differential abilities of NF-E2 proteins in NF-E2 binding, recruiting CBP/p300, disrupting the nucleosomal structure and exerting their trans-activation potency from the TXAS promoter context account for the cell-preferential expression. To test this hypothesis, we propose to: (4) characterize the role of the NF-E2 in altering the nucleosomal structure of TXAS gene and to delineate the TXAS cell-preferential expression using an in vitro chromatin system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “primary pulmonary hypertension” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for primary pulmonary hypertension in the PubMed Central database: •

Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. by Caestecker MD, Meyrick B.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59576

•

Functional Heterogeneity of Bone Morphogenetic Protein Receptor-II Mutants Found in Patients with Primary Pulmonary Hypertension. by Nishihara A, Watabe T, Imamura T, Miyazono K.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124142

•

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. by Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, Block LH.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154449

3 4

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

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

Studies

27

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

A case series of six children with primary pulmonary hypertension. Author(s): Quek SC, Yip CL, Wong ML, Chan KY, Wong CL. Source: Ann Acad Med Singapore. 2001 March; 30(2): 118-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11379407

•

A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. Author(s): Hoeper MM, Olschewski H, Ghofrani HA, Wilkens H, Winkler J, Borst MM, Niedermeyer J, Fabel H, Seeger W. Source: Journal of the American College of Cardiology. 2000 January; 35(1): 176-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636277

•

A gene for primary pulmonary hypertension. Author(s): Wilkins MR, Gibbs JS, Shovlin CL. Source: Lancet. 2000 October 7; 356(9237): 1207-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11072932

•

A new era in the treatment of primary pulmonary hypertension. Author(s): Bailey CL, Channick RN, Rubin LJ. Source: Heart (British Cardiac Society). 2001 March; 85(3): 251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179256

6

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

28

Primary Pulmonary Hypertension

•

A noninvasive assessment of pulmonary perfusion abnormality in patients with primary pulmonary hypertension. Author(s): Ting H, Sun XG, Chuang ML, Lewis DA, Hansen JE, Wasserman K. Source: Chest. 2001 March; 119(3): 824-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11243964

•

A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium. Author(s): Machado RD, Pauciulo MW, Fretwell N, Veal C, Thomson JR, Vilarino Guell C, Aldred M, Brannon CA, Trembath RC, Nichols WC. Source: Genomics. 2000 September 1; 68(2): 220-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10964520

•

A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension. Author(s): Sastry BK, Narasimhan C, Reddy NK, Anand B, Prakash GS, Raju PR, Kumar DN. Source: Indian Heart J. 2002 July-August; 54(4): 410-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462670

•

A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension. Author(s): Robbins IM, Christman BW, Newman JH, Matlock R, Loyd JE. Source: Chest. 1998 November; 114(5): 1269-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9824000

•

Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Author(s): Grunig E, Janssen B, Mereles D, Barth U, Borst MM, Vogt IR, Fischer C, Olschewski H, Kuecherer HF, Kubler W. Source: Circulation. 2000 September 5; 102(10): 1145-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10973844

•

Acute pulmonary trunk dissection in a patient with primary pulmonary hypertension. Author(s): Wunderbaldinger P, Bernhard C, Uffmann M, Kurkciyan I, Senbaklavaci O, Herold CJ. Source: Journal of Computer Assisted Tomography. 2000 January-February; 24(1): 92-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667667

Studies

29

•

Aerosolized iloprost for primary pulmonary hypertension. Author(s): Ewert R, Wensel R, Opitz CF. Source: The New England Journal of Medicine. 2000 November 9; 343(19): 1421-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11183891

•

An unexpected case of primary pulmonary hypertension of the neonate (PPHN). Potential role of topical administration of enoxolone. Author(s): Navarre-Belhassen C, Cambonie G, Boluda C, Hillaire-Buys D. Source: Journal of Perinatal Medicine. 2002; 30(5): 437-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442611

•

Anaesthesia for caesarean section in the presence of severe primary pulmonary hypertension. Author(s): O'Hare R, McLoughlin C, Milligan K, McNamee D, Sidhu H. Source: British Journal of Anaesthesia. 1998 November; 81(5): 790-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10193297

•

Anastomotic pulmonary hypertension after lung transplantation for primary pulmonary hypertension: report of surgical correction. Author(s): Soriano CM, Gaine SP, Conte JV, Fairman RP, White C, Rubin LJ. Source: Chest. 1999 August; 116(2): 564-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453890

•

Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics. Author(s): Abraham WT, Raynolds MV, Badesch DB, Wynne KM, Groves BM, Roden RL, Robertson AD, Lowes BD, Zisman LS, Voelkel NF, Bristow MR, Perryman MB. Source: J Renin Angiotensin Aldosterone Syst. 2003 March; 4(1): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692750

•

Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Author(s): Wensel R, Opitz CF, Anker SD, Winkler J, Hoffken G, Kleber FX, Sharma R, Hummel M, Hetzer R, Ewert R. Source: Circulation. 2002 July 16; 106(3): 319-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12119247

•

Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation. Author(s): Opitz CF, Wensel R, Bettmann M, Schaffarczyk R, Linscheid M, Hetzer R, Ewert R. Source: European Heart Journal. 2003 February; 24(4): 356-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581683

30

Primary Pulmonary Hypertension

•

Association between hyperhomocysteinemia and primary pulmonary hypertension. Author(s): Arroliga AC, Sandur S, Jacobsen DW, Tewari S, Mustafa M, Mascha EJ, Robinson K. Source: Respiratory Medicine. 2003 July; 97(7): 825-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854633

•

Atrial septostomy for severe primary pulmonary hypertension - report on two cases. Author(s): Kurzyna M, Dabrowski M, Torbicki A, Burakowski J, Kuca P, Fijalkowska A, Sikora J. Source: Kardiologia Polska. 2003 January; 58(1): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14502299

•

Autopsy findings of heart and lungs in a patient with primary pulmonary hypertension associated with use of fenfluramine and phentermine. Author(s): Tomita T, Zhao Q. Source: Chest. 2002 February; 121(2): 649-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834685

•

Beneficial hemodynamic effects of oral prostacyclin (PGI2) analogue, beraprost sodium, on a patient with primary pulmonary hypertension--a case report. Author(s): Hashida H, Hamada M, Shigematsu Y, Ikeda S, Kuwahara T, Kawakami H, Hara Y, Kodama K, Kohara K, Hiwada K. Source: Angiology. 1998 February; 49(2): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9482517

•

Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension. Author(s): Rubens C, Ewert R, Halank M, Wensel R, Orzechowski HD, Schultheiss HP, Hoeffken G. Source: Chest. 2001 November; 120(5): 1562-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713135

•

Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension. Author(s): Kaneko FT, Arroliga AC, Dweik RA, Comhair SA, Laskowski D, Oppedisano R, Thomassen MJ, Erzurum SC. Source: American Journal of Respiratory and Critical Care Medicine. 1998 September; 158(3): 917-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9731026

Studies

31

•

Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension. Author(s): Kerstein D, Levy PS, Hsu DT, Hordof AJ, Gersony WM, Barst RJ. Source: Circulation. 1995 April 1; 91(7): 2028-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7534664

•

BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Author(s): Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA 3rd, Newman J, Williams D, Galie N, Manes A, McNeil K, Yacoub M, Mikhail G, Rogers P, Corris P, Humbert M, Donnai D, Martensson G, Tranebjaerg L, Loyd JE, Trembath RC, Nichols WC. Source: American Journal of Human Genetics. 2001 January; 68(1): 92-102. Epub 2000 December 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115378

•

Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. Author(s): De Caestecker M, Meyrick B. Source: Respiratory Research. 2001; 2(4): 193-7. Epub 2001 June 11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11686884

•

Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Author(s): Hoeper MM, Taha N, Bekjarova A, Gatzke R, Spiekerkoetter E. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 August; 22(2): 330-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952269

•

Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. A systematic review of the evidence. Author(s): McCann UD, Seiden LS, Rubin LJ, Ricaurte GA. Source: Jama : the Journal of the American Medical Association. 1997 August 27; 278(8): 666-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272900

•

Cellular and molecular mechanisms responsible for the pathogenesis of primary pulmonary hypertension. Author(s): Rubin LJ. Source: Pediatr Pulmonol Suppl. 1999; 18: 194-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10093141

32

Primary Pulmonary Hypertension

•

Central retinal vein occlusion associated with primary pulmonary hypertension. Author(s): Bhan A, Rennie IG, Higenbottam TW. Source: Retina (Philadelphia, Pa.). 2001; 21(1): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11217943

•

Characteristics of pulmonary artery pressure waveform for differential diagnosis of chronic pulmonary thromboembolism and primary pulmonary hypertension. Author(s): Nakayama Y, Nakanishi N, Sugimachi M, Takaki H, Kyotani S, Satoh T, Okano Y, Kunieda T, Sunagawa K. Source: Journal of the American College of Cardiology. 1997 May; 29(6): 1311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9137229

•

Characteristics of surviving and nonsurviving patients with primary pulmonary hypertension. Author(s): Rich S, Levy PS. Source: The American Journal of Medicine. 1984 April; 76(4): 573-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6711571

•

Characterization of von Willebrand factor in primary pulmonary hypertension. Author(s): Collados MT, Sandoval J, Lopez S, Masso FA, Paez A, Borbolla JR, Montano LF. Source: Heart and Vessels. 1999; 14(5): 246-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10830921

•

Chemokine macrophage inflammatory protein-1alpha mRNA expression in lung biopsy specimens of primary pulmonary hypertension. Author(s): Fartoukh M, Emilie D, Le Gall C, Monti G, Simonneau G, Humbert M. Source: Chest. 1998 July; 114(1 Suppl): 50S-51S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676626

•

Circulating monocytes from patients with primary pulmonary hypertension are hyporesponsive. Author(s): Raychaudhuri B, Bonfield TL, Malur A, Hague K, Kavuru MS, Arroliga AC, Thomassen MJ. Source: Clinical Immunology (Orlando, Fla.). 2002 August; 104(2): 191-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165280

•

Circulatory failure after anesthesia induction in a patient with severe primary pulmonary hypertension. Author(s): Hohn L, Schweizer A, Morel DR, Spiliopoulos A, Licker M. Source: Anesthesiology. 1999 December; 91(6): 1943-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598638

Studies

33

•

Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Author(s): Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, Nakanishi N, Miyatake K. Source: American Journal of Respiratory and Critical Care Medicine. 2000 February; 161(2 Pt 1): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10673190

•

Clinical insights into the pathogenesis of primary pulmonary hypertension. Author(s): Rich S. Source: Chest. 1998 September; 114(3 Suppl): 237S-241S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741575

•

Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension. Author(s): Raffy O, Azarian R, Brenot F, Parent F, Sitbon O, Petitpretz P, Herve P, Duroux P, Dinh-Xuan AT, Simonneau G. Source: Circulation. 1996 February 1; 93(3): 484-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8565165

•

Combined systolic time intervals and M-mode echocardiography in the evaluation of central hemodynamics in primary pulmonary hypertension. Author(s): Leier CV, Sahar D, Hermiller JB, Magorien RD, Unverferth DV. Source: Respiration; International Review of Thoracic Diseases. 1984; 45(4): 422-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6473924

•

Comparison of bronchopulmonary collaterals and collateral blood flow in patients with chronic thromboembolic and primary pulmonary hypertension. Author(s): Endrys J, Hayat N, Cherian G. Source: Heart (British Cardiac Society). 1997 August; 78(2): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9326993

•

Comparison of survival in patients with pulmonary hypertension associated with fenfluramine to patients with primary pulmonary hypertension. Author(s): Rich S, Shillington A, McLaughlin V. Source: The American Journal of Cardiology. 2003 December 1; 92(11): 1366-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636926

34

Primary Pulmonary Hypertension

•

Concurrent pulmonary arterial dissection and saccular aneurysm associated with primary pulmonary hypertension. Author(s): Masuda S, Ishii T, Asuwa N, Ishikawa Y, Kiguchi H, Uchiyama T. Source: Archives of Pathology & Laboratory Medicine. 1996 March; 120(3): 309-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8629914

•

Continuous infusion of epoprostenol improves the net balance between pulmonary endothelin-1 clearance and release in primary pulmonary hypertension. Author(s): Langleben D, Barst RJ, Badesch D, Groves BM, Tapson VF, Murali S, Bourge RC, Ettinger N, Shalit E, Clayton LM, Jobsis MM, Blackburn SD, Crow JW, Stewart DJ, Long W. Source: Circulation. 1999 June 29; 99(25): 3266-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385501

•

Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Author(s): Friedman R, Mears JG, Barst RJ. Source: Circulation. 1997 November 4; 96(9): 2782-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9386137

•

Continuous intravenous prostacyclin for advanced primary pulmonary hypertension. Author(s): Archer-Chicko C. Source: Dimensions of Critical Care Nursing : Dccn. 2000 March-April; 19(2): 14-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10876492

•

Current management of primary pulmonary hypertension. Author(s): De Backer TL, Smedema JP, Carlier SG. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2001; 15(12): 801-17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11784212

•

Current management of primary pulmonary hypertension. Author(s): Klings ES, Farber HW. Source: Drugs. 2001; 61(13): 1945-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11708765

•

Death in a patient with primary pulmonary hypertension after 20 mg of nifedipine. Author(s): Partanen J, Nieminen MS, Luomanmaki K. Source: The New England Journal of Medicine. 1993 September 9; 329(11): 812; Author Reply 812-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8350908

Studies

35

•

Death of a young woman suffering from primary pulmonary hypertension during inhaled nitric oxide therapy. Author(s): Partanen J, Nieminen MS. Source: Archives of Internal Medicine. 1995 April 24; 155(8): 875-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7717799

•

Decarto technique in long-term observation of patients treated for primary pulmonary hypertension. Author(s): Titomir LI, Sakhnova TA, Chazova IE, Barinova NE, Kozhemyakina ES. Source: Bratisl Lek Listy. 1996 September; 97(9): 536-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8948149

•

Decrease in pulmonary artery pressure with slow release nifedipine in Saudi patients with primary pulmonary hypertension. Author(s): Ribeiro PA, Sivanandan V, Shaikh A, Chalak W, Zaman L, Duran CM. Source: Rev Port Cardiol. 1991 May; 10(5): 413-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1910877

•

Detection of familial primary pulmonary hypertension by genetic testing. Author(s): Morse JH, Barst RJ. Source: The New England Journal of Medicine. 1997 July 17; 337(3): 202-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9221353

•

Detrimental effects of verapamil in patients with primary pulmonary hypertension. Author(s): Packer M, Medina N, Yushak M, Wiener I. Source: British Heart Journal. 1984 July; 52(1): 106-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6743418

•

Development of nonspecific interstitial pneumonitis associated with long-term treatment of primary pulmonary hypertension with prostacyclin. Author(s): Kesten S, Dainauskas J, McLaughlin V, Rich S. Source: Chest. 1999 August; 116(2): 566-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453891

•

Development of pulmonary aneurysm in primary pulmonary hypertension: a case report. Author(s): Nienaber CA, Spielmann RP, Montz R, Bleifeld W, Mathey DG. Source: Angiology. 1986 April; 37(4): 319-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3717697

36

Primary Pulmonary Hypertension

•

Diagnosing and treating primary pulmonary hypertension. Author(s): Frazier SK. Source: The Nurse Practitioner. 1999 September; 24(9): 18, 21-2, 25-6 Passim; Quiz 42-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10507069

•

Diagnosis and management of primary pulmonary hypertension. Author(s): Krishnan U. Source: Indian J Pediatr. 2000 March; 67(3 Suppl): S41-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11129920

•

Diagnosis and management of primary pulmonary hypertension. Author(s): Krishnan U. Source: Indian J Pediatr. 2000 July; 67(7): 523-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10957838

•

Dieulafoy's vascular malformation and primary pulmonary hypertension in a 10-yearold girl. Author(s): Robson ME, McLennan J. Source: Histopathology. 1994 September; 25(3): 279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7821897

•

Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension. Author(s): Boger RH, Mugge A, Bode-Boger SM, Heinzel D, Hoper MM, Frolich JC. Source: Int J Clin Pharmacol Ther. 1996 August; 34(8): 323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8864793

•

Dilation and evacuation during the second trimester of pregnancy in a woman with primary pulmonary hypertension. A case report. Author(s): Bowers C, Devine PA, Chervenak FA. Source: J Reprod Med. 1988 September; 33(9): 787-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3172087

•

Direct quantitation of right and left ventricular volumes with nuclear magnetic resonance imaging in patients with primary pulmonary hypertension. Author(s): Boxt LM, Katz J, Kolb T, Czegledy FP, Barst RJ. Source: Journal of the American College of Cardiology. 1992 June; 19(7): 1508-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1593046

Studies

37

•

Disturbances of left-ventricular function in primary pulmonary hypertension. Author(s): Dubiel JP, Pyzik Z, Kolasinska-Kloch W. Source: Acta Med Pol. 1984; 25(1-4): 73-85. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6535385

•

Do patients with primary pulmonary hypertension develop extensive central thrombi? Author(s): Moser KM, Fedullo PF, Finkbeiner WE, Golden J. Source: Circulation. 1995 February 1; 91(3): 741-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7828302

•

Doppler echocardiographic assessment of impaired left ventricular filling in patients with right ventricular pressure overload due to primary pulmonary hypertension. Author(s): Louie EK, Rich S, Brundage BH. Source: Journal of the American College of Cardiology. 1986 December; 8(6): 1298-306. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3782636

•

Double mitral valve orifice and primary pulmonary hypertension. Author(s): Mendelsohn ME, Cole P, Sutton MS. Source: International Journal of Cardiology. 1989 February; 22(2): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2914747

•

Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Author(s): Yuan JX, Aldinger AM, Juhaszova M, Wang J, Conte JV Jr, Gaine SP, Orens JB, Rubin LJ. Source: Circulation. 1998 October 6; 98(14): 1400-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9760294

•

Echocardiographic features of primary pulmonary hypertension. Author(s): Bossone E, Duong-Wagner TH, Paciocco G, Oral H, Ricciardi M, Bach DS, Rubenfire M, Armstrong WF. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 1999 August; 12(8): 655-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10441222

•

Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. Author(s): Raymond RJ, Hinderliter AL, Willis PW, Ralph D, Caldwell EJ, Williams W, Ettinger NA, Hill NS, Summer WR, de Boisblanc B, Schwartz T, Koch G, Clayton LM, Jobsis MM, Crow JW, Long W. Source: Journal of the American College of Cardiology. 2002 April 3; 39(7): 1214-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923049

38

Primary Pulmonary Hypertension

•

Echocardiographic predictors of an adverse response to a nifedipine trial in primary pulmonary hypertension: diminished left ventricular size and leftward ventricular septal bowing. Author(s): Ricciardi MJ, Bossone E, Bach DS, Armstrong WF, Rubenfire M. Source: Chest. 1999 November; 116(5): 1218-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10559078

•

Effect of chronic infusion of epoprostenol on echocardiographic right ventricular myocardial performance index and its relation to clinical outcome in patients with primary pulmonary hypertension. Author(s): Sebbag I, Rudski LG, Therrien J, Hirsch A, Langleben D. Source: The American Journal of Cardiology. 2001 November 1; 88(9): 1060-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704014

•

Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. Author(s): Nagaya N, Uematsu M, Okano Y, Satoh T, Kyotani S, Sakamaki F, Nakanishi N, Miyatake K, Kunieda T. Source: Journal of the American College of Cardiology. 1999 October; 34(4): 1188-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10520811

•

Effective immunosuppressive therapy in a patient with primary pulmonary hypertension. Author(s): Bellotto F, Chiavacci P, Laveder F, Angelini A, Thiene G, Marcolongo R. Source: Thorax. 1999 April; 54(4): 372-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10092701

•

Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Author(s): Wensel R, Opitz CF, Ewert R, Bruch L, Kleber FX. Source: Circulation. 2000 May 23; 101(20): 2388-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10821815

•

Effects of long-term infusion of prostacyclin on exercise performance in patients with primary pulmonary hypertension. Author(s): Wax D, Garofano R, Barst RJ. Source: Chest. 1999 October; 116(4): 914-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10531153

Studies

39

•

Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension. Author(s): Langleben D, Christman BW, Barst RJ, Dias VC, Galie N, Higenbottam TW, Kneussl M, Korducki L, Naeije R, Riedel A, Simonneau G, Hirsch AM, Rich S, Robbins IM, Oudiz R, McGoon MD, Badesch DB, Levy RD, Mehta S, Seeger W, Soler M. Source: American Heart Journal. 2002 May; 143(5): E4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040360

•

Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension. Author(s): McLaughlin VV, Gaine SP, Barst RJ, Oudiz RJ, Bourge RC, Frost A, Robbins IM, Tapson VF, McGoon MD, Badesch DB, Sigman J, Roscigno R, Blackburn SD, Arneson C, Rubin LJ, Rich S; Treprostinil Study Group. Source: Journal of Cardiovascular Pharmacology. 2003 February; 41(2): 293-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548091

•

Endothelin-1 and functional tissue factor: a possible relationship with severity in primary pulmonary hypertension. Author(s): Collados MT, Velazquez B, Borbolla JR, Sandoval J, Masso F, Montano LF, Guarner V. Source: Heart and Vessels. 2003 March; 18(1): 12-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644876

•

Epoprostenol in primary pulmonary hypertension. Author(s): Herner SJ, Mauro LS. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 340-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10200860

•

Epoprostenol therapy for primary pulmonary hypertension after rejection of a single donor lung. Author(s): Roeleveld RJ, Vonk Noordegraaf A, van der Bij W, Postmus PE, Boonstra A. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 January; 21(1): 192-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12570128

•

Epoprostenol therapy for primary pulmonary hypertension. Author(s): Cheever KH, Kitzes B, Genthner D. Source: Critical Care Nurse. 1999 August; 19(4): 20-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10614244

40

Primary Pulmonary Hypertension

•

Esophageal variceal ligation for esophageal variceal hemorrhage in a patient with portal and primary pulmonary hypertension complicating myelofibrosis. Author(s): Lee WC, Lin HC, Tsay SH, Yang YY, Hou MC, Lee FY, Chang FY, Lee SD. Source: Digestive Diseases and Sciences. 2001 April; 46(4): 915-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11330433

•

Etiology and pathogenesis of primary pulmonary hypertension: a perspective. Author(s): Fishman AP. Source: Chest. 1998 September; 114(3 Suppl): 242S-247S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741576

•

Exercise pathophysiology in patients with primary pulmonary hypertension. Author(s): Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Source: Circulation. 2001 July 24; 104(4): 429-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11468205

•

Exercise testing in children with primary pulmonary hypertension. Author(s): Garofano RP, Barst RJ. Source: Pediatric Cardiology. 1999 January-February; 20(1): 61-4; Discussion 65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9861081

•

Expression of human herpesvirus 8 in primary pulmonary hypertension. Author(s): Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, Geraci MW, Brown KK, Routes JM, Tuder RM, Voelkel NF. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1113-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679525

•

Extracorporeal membrane oxygenation support for single-lung transplantation in patients with primary pulmonary hypertension. Author(s): Ko WJ, Chen YS, Luh SP, Lee YC, Chu SH. Source: Transplantation Proceedings. 1999 February-March; 31(1-2): 166-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10083060

•

Factor V Leiden is not common in patients diagnosed with primary pulmonary hypertension. Author(s): Elliott CG, Leppert MF, Alexander GJ, Ward K, Nelson L, Pietra GG. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 November; 12(5): 1177-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9864017

Studies

41

•

Factors that influence the outcome of primary pulmonary hypertension. Author(s): Rozkovec A, Montanes P, Oakley CM. Source: British Heart Journal. 1986 May; 55(5): 449-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3707785

•

Familial association of primary pulmonary hypertension and a new low-oxygen affinity beta-chain hemoglobinopathy, Hb Washtenaw. Author(s): Wille RT, Krishnan K, Cooney KA, Bach DS, Martinez F. Source: Chest. 1996 March; 109(3): 848-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8617104

•

Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Author(s): Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, Hodge SE, Knowles JA. Source: American Journal of Human Genetics. 2000 September; 67(3): 737-44. Epub 2000 July 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10903931

•

Familial primary pulmonary hypertension and associated ocular findings. Author(s): Saran BR, Brucker AJ, Bandello F, Verougstraete C. Source: Retina (Philadelphia, Pa.). 2001; 21(1): 34-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11217927

•

Familial primary pulmonary hypertension locus mapped to chromosome 2q31-q32. Author(s): Morse JH, Jones AC, Barst RJ, Hodge SE, Wilhelmsen KC, Nygaard TG. Source: Chest. 1998 July; 114(1 Suppl): 57S-58S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676630

•

Familial primary pulmonary hypertension. Author(s): Shanmugasundaram S. Source: Indian Heart J. 2002 March-April; 54(2): 193-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12086385

•

Familial primary pulmonary hypertension: clinical patterns. Author(s): Loyd JE, Primm RK, Newman JH. Source: Am Rev Respir Dis. 1984 January; 129(1): 194-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6703480

42

Primary Pulmonary Hypertension

•

Familial primary pulmonary hypertension--report of two siblings. Author(s): Kodama K, Hamada M, Shigematsu Y, Suzuki M, Hiwada K, Hayashi Y, Hashimoto H, Hashimoto H, Sugita A. Source: Jpn J Med. 1991 May-June; 30(3): 273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1833576

•

Familial pulmonary capillary hemangiomatosis resulting in primary pulmonary hypertension. Author(s): Langleben D, Heneghan JM, Batten AP, Wang NS, Fitch N, Schlesinger RD, Guerraty A, Rouleau JL. Source: Annals of Internal Medicine. 1988 July 15; 109(2): 106-9. Erratum In: Ann Intern Med 1988 September 1; 109(5): 439. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3382104

•

Familial pulmonary hypertension in association with an abnormal hemoglobin. Insights into the pathogenesis of primary pulmonary hypertension. Author(s): Rich S, Hart K. Source: Chest. 1991 May; 99(5): 1208-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1708327

•

Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome. Author(s): Korniszewski L, Kurzyna M, Stolarski B, Torbicki A, Smerdel A, Ploski R. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 October; 22(4): 709-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582926

•

Felodipine in primary pulmonary hypertension. Report of two cases. Author(s): Arnman K, Ryden L, Smedgard P, Thorhallsson E. Source: Acta Med Scand. 1984; 215(3): 275-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6731040

•

Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension. Author(s): Eisenberg PR, Lucore C, Kaufman L, Sobel BE, Jaffe AS, Rich S. Source: Circulation. 1990 September; 82(3): 841-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2394005

Studies

43

•

Fine mapping of PPH1, a gene for familial primary pulmonary hypertension, to a 3cM region on chromosome 2q33. Author(s): Deng Z, Haghighi F, Helleby L, Vanterpool K, Horn EM, Barst RJ, Hodge SE, Morse JH, Knowles JA. Source: American Journal of Respiratory and Critical Care Medicine. 2000 March; 161(3 Pt 1): 1055-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10712363

•

Fine specificity of anti-fibrillin-1 autoantibodies in primary pulmonary hypertension syndrome. Author(s): Morse JH, Antohi S, Kasturi K, Saito S, Fotino M, Humbert M, Simonneau G, Basst RJ, Bona CA. Source: Scandinavian Journal of Immunology. 2000 June; 51(6): 607-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10849372

•

Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension. Author(s): Hinderliter AL, Willis PW 4th, Long W, Clarke WR, Ralph D, Caldwell EJ, Williams W, Ettinger NA, Hill NS, Summer WR, de Biosblanc B, Koch G, Li S, Clayton LM, Jobsis MM, Crow JW. Source: The American Journal of Cardiology. 1999 August 15; 84(4): 481-4, A10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468096

•

Frequency and severity of tricuspid regurgitation determined by Doppler echocardiography in primary pulmonary hypertension. Author(s): Hinderliter AL, Willis PW 4th, Long WA, Clarke WR, Ralph D, Caldwell EJ, Williams W, Ettinger NA, Hill NS, Summer WR, de Boisblanc B, Koch G, Li S, Clayton LM, Jobsis MM, Crow JW; PPH Study Group. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 1033-7, A9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686360

•

Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Author(s): Rudarakanchana N, Flanagan JA, Chen H, Upton PD, Machado R, Patel D, Trembath RC, Morrell NW. Source: Human Molecular Genetics. 2002 June 15; 11(13): 1517-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12045205

•

Functional heterogeneity of bone morphogenetic protein receptor-II mutants found in patients with primary pulmonary hypertension. Author(s): Nishihara A, Watabe T, Imamura T, Miyazono K. Source: Molecular Biology of the Cell. 2002 September; 13(9): 3055-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221115

44

Primary Pulmonary Hypertension

•

Gas exchange detection of exercise-induced right-to-left shunt in patients with primary pulmonary hypertension. Author(s): Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Source: Circulation. 2002 January 1; 105(1): 54-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11772876

•

Gas exchange responses to continuous incremental cycle ergometry exercise in primary pulmonary hypertension in humans. Author(s): Riley MS, Porszasz J, Engelen MP, Brundage BH, Wasserman K. Source: European Journal of Applied Physiology. 2000 September; 83(1): 63-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11072775

•

Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis. Author(s): Geraci MW, Moore M, Gesell T, Yeager ME, Alger L, Golpon H, Gao B, Loyd JE, Tuder RM, Voelkel NF. Source: Circulation Research. 2001 March 30; 88(6): 555-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11282888

•

Gene for familial primary pulmonary hypertension identified. Author(s): SoRelle R. Source: Circulation. 2000 August 8; 102(6): E9010-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950623

•

Gene for primary pulmonary hypertension identified. Author(s): McCarthy M. Source: Lancet. 2000 August 5; 356(9228): 489. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10981899

•

Gene mutation linked to primary pulmonary hypertension. Author(s): Cockey CD. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2000 October-November; 4(5): 17-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11898153

•

Genetic anticipation and abnormal gender ratio at birth in familial primary pulmonary hypertension. Author(s): Loyd JE, Butler MG, Foroud TM, Conneally PM, Phillips JA 3rd, Newman JH. Source: American Journal of Respiratory and Critical Care Medicine. 1995 July; 152(1): 93-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7599869

Studies

45

•

Genetic clues to the cause of primary pulmonary hypertension. Author(s): Loscalzo J. Source: The New England Journal of Medicine. 2001 August 2; 345(5): 367-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484696

•

Genetics and immunogenetic aspects of primary pulmonary hypertension. Author(s): Barst RJ, Loyd JE. Source: Chest. 1998 September; 114(3 Suppl): 231S-236S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741574

•

Genetics of primary pulmonary hypertension. Author(s): Thomas AQ, Gaddipati R, Newman JH, Loyd JE. Source: Clinics in Chest Medicine. 2001 September; 22(3): 477-91, Ix. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590842

•

Graded balloon dilation atrial septostomy in severe primary pulmonary hypertension. A therapeutic alternative for patients nonresponsive to vasodilator treatment. Author(s): Sandoval J, Gaspar J, Pulido T, Bautista E, Martinez-Guerra ML, Zeballos M, Palomar A, Gomez A. Source: Journal of the American College of Cardiology. 1998 August; 32(2): 297-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9708453

•

Heart-lung transplantation for primary pulmonary hypertension. Author(s): Whyte RI, Robbins RC, Altinger J, Barlow CW, Doyle R, Theodore J, Reitz BA. Source: The Annals of Thoracic Surgery. 1999 April; 67(4): 937-41; Discussion 941-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10320232

•

Hemodynamic correlates of exercise function in patients with primary pulmonary hypertension. Author(s): Rhodes J, Barst RJ, Garofano RP, Thoele DG, Gersony WM. Source: Journal of the American College of Cardiology. 1991 December; 18(7): 1738-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1960322

•

Hemodynamic effects of nifedipine at rest and during exercise in primary pulmonary hypertension. Author(s): Olivari MT, Levine TB, Weir EK, Cohn JN. Source: Chest. 1984 July; 86(1): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6734275

46

Primary Pulmonary Hypertension

•

Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension. Author(s): Leuchte HH, Schwaiblmair M, Baumgartner RA, Neurohr CF, Kolbe T, Behr J. Source: Chest. 2004 February; 125(2): 580-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769741

•

Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Author(s): Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC. Source: Nature Genetics. 2000 September; 26(1): 81-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10973254

•

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

•

High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium. Author(s): Delcroix M, Kurz X, Walckiers D, Demedts M, Naeije R. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 August; 12(2): 271-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9727773

•

High plasma serotonin levels in primary pulmonary hypertension. Effect of long-term epoprostenol (prostacyclin) therapy. Author(s): Kereveur A, Callebert J, Humbert M, Herve P, Simonneau G, Launay JM, Drouet L. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 October; 20(10): 2233-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11031209

•

High prevalence of hypothyroidism in patients with primary pulmonary hypertension. Author(s): Curnock AL, Dweik RA, Higgins BH, Saadi HF, Arroliga AC. Source: The American Journal of the Medical Sciences. 1999 November; 318(5): 289-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10555089

Studies

47

•

High-altitude pulmonary edema with primary pulmonary hypertension. Author(s): Naeije R, De Backer D, Vachiery JL, De Vuyst P. Source: Chest. 1996 July; 110(1): 286-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8681646

•

Histopathologic findings of lung vessels in five children with primary pulmonary hypertension. Author(s): Sato T, Akiba T, Suzuki H, Nakasato M, Sato S, Yoshikawa M, Yamaki S. Source: The Tohoku Journal of Experimental Medicine. 1994 January; 172(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8036624

•

HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Author(s): Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, Hirschel B, Luthy R. Source: American Journal of Respiratory and Critical Care Medicine. 1997 March; 155(3): 990-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9117037

•

Hormone replacement therapy: a possible risk factor in carriers of familial primary pulmonary hypertension. Author(s): Morse JH, Horn EM, Barst RJ. Source: Chest. 1999 September; 116(3): 847. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10492306

•

How to manage primary pulmonary hypertension. Giving hope to patients with a life-threatening illness. Author(s): Ricciardi MJ, Rubenfire M. Source: Postgraduate Medicine. 1999 March; 105(3): 45-8, 51-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10086033

•

HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema. Author(s): Golpon HA, Geraci MW, Moore MD, Miller HL, Miller GJ, Tuder RM, Voelkel NF. Source: American Journal of Pathology. 2001 March; 158(3): 955-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11238043

•

Human immunodeficiency virus and primary pulmonary hypertension. Author(s): Arunabh, Edasery B. Source: The Western Journal of Medicine. 1993 December; 159(6): 708-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8128697

48

Primary Pulmonary Hypertension

•

Hyperplasia of pulmonary artery smooth muscle cells is causally related to overexpression of the serotonin transporter in primary pulmonary hypertension. Author(s): Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simonneau G, Dartevelle P, Hamon M, Adnot S. Source: Chest. 2002 March; 121(3 Suppl): 97S-98S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893722

•

Hypothyroidism and primary pulmonary hypertension. Author(s): Kashyap AS, Kashyap S. Source: Circulation. 2001 November 13; 104(20): E103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11705834

•

Hypothyroidism and primary pulmonary hypertension. Author(s): Fisher J. Source: Annals of Internal Medicine. 1994 January 15; 120(2): 167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8256982

•

Hypothyroidism and primary pulmonary hypertension: an autoimmune pathogenetic link? Author(s): Badesch DB, Wynne KM, Bonvallet S, Voelkel NF, Ridgway C, Groves BM. Source: Annals of Internal Medicine. 1993 July 1; 119(1): 44-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8498763

•

Images in clinical medicine. Dilatation of the pulmonary arteries in primary pulmonary hypertension. Author(s): Lang IM, Kneussl MP. Source: The New England Journal of Medicine. 1996 February 1; 334(5): 302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8532026

•

Imaging in primary pulmonary hypertension. Author(s): Chugh IM, Agarwal AK, Sharma P, Chanana BB, Shah A. Source: Indian J Chest Dis Allied Sci. 1998 July-September; 40(3): 195-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9919839

•

Impaired left ventricular filling due to right ventricular pressure overload in primary pulmonary hypertension: noninvasive monitoring using MRI. Author(s): Marcus JT, Vonk Noordegraaf A, Roeleveld RJ, Postmus PE, Heethaar RM, Van Rossum AC, Boonstra A. Source: Chest. 2001 June; 119(6): 1761-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11399703

Studies

49

•

Impaired release of ATP from red blood cells of humans with primary pulmonary hypertension. Author(s): Sprague RS, Stephenson AH, Ellsworth ML, Keller C, Lonigro AJ. Source: Experimental Biology and Medicine (Maywood, N.J.). 2001 May; 226(5): 434-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11393171

•

Impairment of endothelium-dependent pulmonary vasodilation in patients with primary pulmonary hypertension. Author(s): Brett SJ, Simon J, Gibbs R, Pepper JR, Evans TW. Source: Thorax. 1996 January; 51(1): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8658378

•

Increased levels of prostaglandin D(2) suggest macrophage activation in patients with primary pulmonary hypertension. Author(s): Robbins IM, Barst RJ, Rubin LJ, Gaine SP, Price PV, Morrow JD, Christman BW. Source: Chest. 2001 November; 120(5): 1639-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713147

•

Inhaled nitric oxide and heparin for infantile primary pulmonary hypertension. Author(s): Atz AM, Wessel DL. Source: Lancet. 1998 June 6; 351(9117): 1701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9734889

•

Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Author(s): Sitbon O, Humbert M, Jagot JL, Taravella O, Fartoukh M, Parent F, Herve P, Simonneau G. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 August; 12(2): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9727772

•

Inhaled nitric oxide for primary pulmonary hypertension in pregnancy. Author(s): Lam GK, Stafford RE, Thorp J, Moise KJ Jr, Cairns BA. Source: Obstetrics and Gynecology. 2001 November; 98(5 Pt 2): 895-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704193

•

Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective agent for predicting response to nifedipine. Author(s): Ricciardi MJ, Knight BP, Martinez FJ, Rubenfire M. Source: Journal of the American College of Cardiology. 1998 October; 32(4): 1068-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9768734

50

Primary Pulmonary Hypertension

•

Inhaled nitric oxide is unlikely to have contributed to the death of a young woman suffering from primary pulmonary hypertension. Author(s): Morris GN. Source: Archives of Internal Medicine. 1996 March 11; 156(5): 588. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8604968

•

Initial steps toward consensus in the management of primary pulmonary hypertension. Author(s): Koniaris L. Source: Chest. 1998 November; 114(5): 1234-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9823992

•

Insights into the genetic and molecular basis of primary pulmonary hypertension. Author(s): Trembath RC, Harrison R. Source: Pediatric Research. 2003 June; 53(6): 883-8. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621102

•

Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium. Author(s): Castro PF, Bourge RC, McGiffin DC, Benza RL, Fan P, Pinkard NB, McGoon MD. Source: Chest. 1998 July; 114(1): 334-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9674493

•

Intratracheal prostacyclin for resuscitation in primary pulmonary hypertension. Author(s): Haas NA, Schulze-Neick I, Lange PE. Source: Lancet. 1995 September 2; 346(8975): 643. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7651035

•

Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertension. Author(s): Nakamoto A, Yoshitake J, Hase T, Harasawa H, Okamoto S, Fuse D, Kawasaki R, Kuga H, Kishiro I, Machida S, Oshiro H, Totsuka M, Kaneko N. Source: Respirology (Carlton, Vic.). 2000 March; 5(1): 71-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728735

•

Intravascular ultrasound of the elastic pulmonary arteries: a new approach for the evaluation of primary pulmonary hypertension. Author(s): Rodes-Cabau J, Domingo E, Roman A, Majo J, Lara B, Padilla F, Anivarro I, Angel J, Tardif JC, Soler-Soler J. Source: Heart (British Cardiac Society). 2003 March; 89(3): 311-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591838

Studies

51

•

Intravenous epoprostenol for primary pulmonary hypertension. Author(s): Schulze-Neick I, Lange PE, Haas NA. Source: The New England Journal of Medicine. 1996 May 30; 334(22): 1477; Author Reply 1477-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8618596

•

Intravenous epoprostenol for primary pulmonary hypertension. Author(s): Higenbottam T. Source: The New England Journal of Medicine. 1996 May 30; 334(22): 1477; Author Reply 1477-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8618595

•

Intravenous epoprostenol: a new therapy for primary pulmonary hypertension. Author(s): Sabo JA, Nord CP. Source: Critical Care Nurse. 2000 December; 20(6): 31-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11878257

•

Lack of association between angiotensin converting enzyme (ACE) genotype, serum ACE activity, and haemodynamics in patients with primary pulmonary hypertension. Author(s): Hoeper MM, Tacacs A, Stellmacher U, Lichtinghagen R. Source: Heart (British Cardiac Society). 2003 April; 89(4): 445-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639879

•

Lack of beneficial effects of L-arginine infusion in primary pulmonary hypertension. Author(s): Surdacki A, Zmudka K, Bieron K, Kostka-Trabka E, Dubiel JS, Gryglewski RJ. Source: Wiener Klinische Wochenschrift. 1994; 106(16): 521-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7975663

•

Left main coronary artery compression during primary pulmonary hypertension. Author(s): Patrat JF, Jondeau G, Dubourg O, Lacombe P, Rigaud M, Bourdarias JP, Gandjbakhch I. Source: Chest. 1997 September; 112(3): 842-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9315824

•

Linkage analysis in a large family with primary pulmonary hypertension: genetic heterogeneity and a second primary pulmonary hypertension locus on 2q31-32. Author(s): Janssen B, Rindermann M, Barth U, Miltenberger-Miltenyi G, Mereles D, Abushi A, Seeger W, Kubler W, Bartram CR, Grunig E. Source: Chest. 2002 March; 121(3 Suppl): 54S-56S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893685

52

Primary Pulmonary Hypertension

•

Linking a serotonin transporter polymorphism to vascular smooth muscle proliferation in patients with primary pulmonary hypertension. Author(s): Rabinovitch M. Source: The Journal of Clinical Investigation. 2001 October; 108(8): 1109-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11602617

•

Lipid mediator dysregulation in primary pulmonary hypertension. Author(s): Christman BW. Source: Chest. 1998 September; 114(3 Suppl): 205S-207S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741570

•

Living-donor single-lobe lung transplantation for primary pulmonary hypertension in a child. Author(s): Date H, Sano Y, Aoe M, Matsubara H, Kusano K, Goto K, Tedoriya T, Shimizu N. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 June; 123(6): 1211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063472

•

Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32. Author(s): Nichols WC, Koller DL, Slovis B, Foroud T, Terry VH, Arnold ND, Siemieniak DR, Wheeler L, Phillips JA 3rd, Newman JH, Conneally PM, Ginsburg D, Loyd JE. Source: Nature Genetics. 1997 March; 15(3): 277-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9054941

•

Long-term beneficial effect of nifedipine in primary pulmonary hypertension. Author(s): Lunde P, Rasmussen K. Source: American Heart Journal. 1984 August; 108(2): 415-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6464979

•

Long-term continuous intravenous infusion of prostacyclin for severe primary pulmonary hypertension. Author(s): Okano Y, Senju S, Tsutsui Y, Kyotani S, Ishibashi M, Yoshida M, Kunieda T. Source: Intern Med. 1997 November; 36(11): 794-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9392352

•

Long-term favourable effect of nifedipine in primary pulmonary hypertension. Report of a case with hemodynamic evaluation after 3 and after 16 months and with clinical follow-up during 36 months. Author(s): Musante R, Di Donato M. Source: G Ital Cardiol. 1985 November; 15(11): 1110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3830769

Studies

53

•

Long-term inhalation of nitric oxide for a patient with primary pulmonary hypertension. Author(s): Koh E, Niimura J, Nakamura T, Yamakage H, Takahashi H. Source: Japanese Circulation Journal. 1998 December; 62(12): 940-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890209

•

Long-term prostacyclin reduces pulmonary vascular resistance in severe primary pulmonary hypertension. Author(s): Barst RJ. Source: Clin Exp Rheumatol. 1998 May-June; 16(3): 253-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631745

•

Long-term survival in primary pulmonary hypertension. Author(s): Tahir MZ. Source: Hosp Pract (Off Ed). 1992 November 15; 27(11): 219-22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1429942

•

Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. Author(s): Hoeper MM, Schwarze M, Ehlerding S, Adler-Schuermeyer A, Spiekerkoetter E, Niedermeyer J, Hamm M, Fabel H. Source: The New England Journal of Medicine. 2000 June 22; 342(25): 1866-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10861321

•

Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin). Author(s): Higenbottam T, Wheeldon D, Wells F, Wallwork J. Source: Lancet. 1984 May 12; 1(8385): 1046-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6143976

•

Low or absent peptidase expression in plexiform lesions of primary pulmonary hypertension. Author(s): Cohen AJ, Cool C, Gorg S, Gilman LB, Tuder RM, Miller YE, Voelkel NF. Source: Chest. 1998 July; 114(1 Suppl): 30S-31S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676613

•

Lung scintigraphy in pulmonary capillary hemangiomatosis. A rare disorder causing primary pulmonary hypertension. Author(s): Rush C, Langleben D, Schlesinger RD, Stern J, Wang NS, Lamoureux E. Source: Clinical Nuclear Medicine. 1991 December; 16(12): 913-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1769171

54

Primary Pulmonary Hypertension

•

Lung transplantation for primary pulmonary hypertension and giant pulmonary artery aneurysm. Author(s): Wekerle T, Klepetko W, Taghavi S, Birsan T. Source: The Annals of Thoracic Surgery. 1998 March; 65(3): 825-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9527223

•

Lung transplantation for primary pulmonary hypertension. Author(s): Trulock EP. Source: Clinics in Chest Medicine. 2001 September; 22(3): 583-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590850

•

Magnitude and implications of spontaneous hemodynamic variability in primary pulmonary hypertension. Author(s): Rich S, D'Alonzo GE, Dantzker DR, Levy PS. Source: The American Journal of Cardiology. 1985 January 1; 55(1): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3966375

•

Malignant infantile osteopetrosis and primary pulmonary hypertension: a new combination? Author(s): Kasow KA, Bonfim C, Asch J, Margolis DA, Jenkins J, Tamburro RF, Handgretinger R, Horwitz EM. Source: Pediatric Blood & Cancer. 2004 February; 42(2): 190-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752886

•

Management of primary pulmonary hypertension. Author(s): Oakley CM. Source: British Heart Journal. 1985 January; 53(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3966945

•

Managing patients with primary pulmonary hypertension: prostacyclin therapy. Author(s): Albert NM, Hague K. Source: American Journal of Critical Care : an Official Publication, American Association of Critical-Care Nurses. 1997 July; 6(4): 274-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9215424

•

Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31-q32. Author(s): Morse JH, Jones AC, Barst RJ, Hodge SE, Wilhelmsen KC, Nygaard TG. Source: Circulation. 1997 June 17; 95(12): 2603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9193425

Studies

55

•

Maternal primary pulmonary hypertension associated with pregnancy. Author(s): Martinez JM, Comas C, Sala X, Gratacos E, Torres PJ, Fortuny A. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1994 April; 54(2): 143-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8070600

•

Mechanics of breathing in patients with primary pulmonary hypertension. Author(s): Yernault JC, De Troyer A. Source: Am Rev Respir Dis. 1979 February; 119(2): 320-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=434604

•

Medical management of primary pulmonary hypertension. Author(s): McLaughlin VV. Source: Expert Opinion on Pharmacotherapy. 2002 February; 3(2): 159-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11829729

•

Medical management of primary pulmonary hypertension. Author(s): Kneussl MP, Lang IM, Brenot FP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1996 November; 9(11): 2401-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8947091

•

Medical treatment of primary pulmonary hypertension: a bridge to transplantation? Author(s): Rich S. Source: The American Journal of Cardiology. 1995 January 19; 75(3): 63A-66A. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7840057

•

Microangiopathic hemolytic anemia and thrombocytopenia in primary pulmonary hypertension. Author(s): Stuard ID, Heusinkveld RS, Moss AJ. Source: The New England Journal of Medicine. 1972 October 26; 287(17): 869-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5071968

•

Microarteriographic studies of primary pulmonary hypertension. A quantitative approach in two patients. Author(s): Reeves JT, Noonan JA. Source: Arch Pathol. 1973 January; 95(1): 50-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4682030

56

Primary Pulmonary Hypertension

•

Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension. Author(s): Yeager ME, Halley GR, Golpon HA, Voelkel NF, Tuder RM. Source: Circulation Research. 2001 January 19; 88(1): E2-E11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11139485

•

Midsystolic closure of the aortic valve in primary pulmonary hypertension. Author(s): Doi YL, Bishop RL, Sugiura T, Spodick DH. Source: Chest. 1981 June; 79(6): 710-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7194770

•

Misleading capnography in primary pulmonary hypertension. Author(s): Yogasakaran BS. Source: Journal of Cardiothoracic and Vascular Anesthesia. 1992 June; 6(3): 385-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611009

•

Mixed expired nitric oxide in primary pulmonary hypertension in relation to lung diffusion capacity. Author(s): Cremona G, Higenbottam T, Borland C, Mist B. Source: Qjm : Monthly Journal of the Association of Physicians. 1994 September; 87(9): 547-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7953503

•

Moderate primary pulmonary hypertension in patients undergoing liver transplantation. Author(s): Taura P, Garcia-Valdecasas JC, Beltran J, Izquierdo E, Navasa M, Sala-Blanch J, Mas A, Balust J, Grande L, Visa J. Source: Anesthesia and Analgesia. 1996 October; 83(4): 675-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8831302

•

Mortality from primary pulmonary hypertension in the United States, 1979-1996. Author(s): Lilienfeld DE, Rubin LJ. Source: Chest. 2000 March; 117(3): 796-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10713009

•

Moya-Moya syndrome and primary pulmonary hypertension in childhood. Author(s): Kapusta L, Daniels O, Renier WO. Source: Neuropediatrics. 1990 August; 21(3): 162-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2234323

Studies

57

•

Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred. Author(s): Newman JH, Wheeler L, Lane KB, Loyd E, Gaddipati R, Phillips JA 3rd, Loyd JE. Source: The New England Journal of Medicine. 2001 August 2; 345(5): 319-24. Erratum In: N Engl J Med 2001 November 15; 345(20): 1506. N Engl J Med 2002 April 18; 346(16): 1258. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484688

•

Natural history of pulmonary hemodynamics in primary pulmonary hypertension. Author(s): Kanemoto N. Source: American Heart Journal. 1987 August; 114(2): 407-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3604899

•

New concepts in the treatment of primary pulmonary hypertension. Author(s): Rubin LJ. Source: Md Med J. 1991 March; 40(3): 209-11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2008166

•

New insights into the pathogenesis and treatment of primary pulmonary hypertension. Author(s): Rudarakanchana N, Trembath RC, Morrell NW. Source: Thorax. 2001 November; 56(11): 888-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11641516

•

New therapies for primary pulmonary hypertension. Author(s): Butt AY, Higenbottam T. Source: Chest. 1994 February; 105(2 Suppl): 21S-25S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8110298

•

Nifedipine and primary pulmonary hypertension. Author(s): Vacek JL. Source: Annals of Internal Medicine. 1984 March; 100(3): 458-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6696367

•

Nifedipine in primary pulmonary hypertension. Author(s): Tobey MA. Source: Journal of the American College of Cardiology. 1984 June; 3(6): 1581-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6715717

58

Primary Pulmonary Hypertension

•

Nifedipine in the treatment of primary pulmonary hypertension. Author(s): Wise JR Jr. Source: American Heart Journal. 1983 April; 105(4): 693-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6220593

•

Nitric oxide and prostacyclin treatment of an infant with primary pulmonary hypertension. Author(s): Ivy DD, Wiggins JW, Badesch DB, Kinsella JP, Kelminson LL, Abman SH. Source: The American Journal of Cardiology. 1994 August 15; 74(4): 414-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059714

•

Nocturnal hypoxemia is common in primary pulmonary hypertension. Author(s): Rafanan AL, Golish JA, Dinner DS, Hague LK, Arroliga AC. Source: Chest. 2001 September; 120(3): 894-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555526

•

Nocturnal periodic breathing in primary pulmonary hypertension. Author(s): Schulz R, Baseler G, Ghofrani HA, Grimminger F, Olschewski H, Seeger W. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 April; 19(4): 658-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11998995

•

Nodular regenerative hyperplasia of the liver associated with primary pulmonary hypertension. Author(s): Yutani C, Imakita M, Ishibashi-Ueda H, Okubo S, Naito M, Kunieda T. Source: Human Pathology. 1988 June; 19(6): 726-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3378792

•

Noninvasive differential diagnosis between chronic pulmonary thromboembolism and primary pulmonary hypertension by means of Doppler ultrasound measurement. Author(s): Nakayama Y, Sugimachi M, Nakanishi N, Takaki H, Okano Y, Satoh T, Miyatake K, Sunagawa K. Source: Journal of the American College of Cardiology. 1998 May; 31(6): 1367-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9581735

•

Noninvasive evaluation of acute effects of oral diltiazem in primary pulmonary hypertension--a preliminary study. Author(s): Misra M, Bajaj V, Kumar N, Puri VK. Source: Indian Heart J. 1986 March-April; 38(2): 114-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3557502

Studies

59

•

Novel nonsense mutation of the BMPR-II gene in a Japanese patient with familial primary pulmonary hypertension. Author(s): Uehara R, Suzuki H, Kurokawa N, Urashima T, Fujiwara M, Matoba M, Eto Y. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 August; 44(4): 433-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139571

•

Obstetric anaesthesia in patients with primary pulmonary hypertension. Author(s): Weeks SK, Smith JB. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1991 October; 38(7): 814-6. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1742813

•

One-year continuous inhaled nitric oxide for primary pulmonary hypertension. Author(s): Perez-Penate G, Julia-Serda G, Pulido-Duque JM, Gorriz-Gomez E, CabreraNavarro P. Source: Chest. 2001 March; 119(3): 970-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11243987

•

Ophthalmologic complications in primary pulmonary hypertension. Author(s): Van Camp G, Renard M, Verougstraete C, Bernard R. Source: Chest. 1990 December; 98(6): 1543-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2245717

•

Oral hydralazine therapy for primary pulmonary hypertension. Author(s): Rubin LJ, Peter RH. Source: The New England Journal of Medicine. 1980 January 10; 302(2): 69-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7350435

•

Orally active prostacyclin analogue in primary pulmonary hypertension. Author(s): Okano Y, Yoshioka T, Shimouchi A, Satoh T, Kunieda T. Source: Lancet. 1997 May 10; 349(9062): 1365. Erratum In: Lancet 1997 November 8; 350(9088): 1406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9149701

•

Orthotopic liver transplantation in a patient with primary pulmonary hypertension. Author(s): Liu G, Knudsen KE, Secher NH. Source: Anaesthesia and Intensive Care. 1996 December; 24(6): 714-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8971323

60

Primary Pulmonary Hypertension

•

Ortner's syndrome associated with primary pulmonary hypertension. Author(s): Kagal AE, Shenoy PN, Nair KG. Source: Journal of Postgraduate Medicine. 1975 April; 21(2): 91-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=126321

•

Overdosing with prostacyclin in primary pulmonary hypertension. Author(s): Wasserman K, Oudiz R. Source: Journal of the American College of Cardiology. 2000 June; 35(7): 1995-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10841256

•

Oxidative stress in patients with primary pulmonary hypertension. Author(s): Irodova NL, Lankin VZ, Konovalova GK, Kochetov AG, Chazova IE. Source: Bulletin of Experimental Biology and Medicine. 2002 June; 133(6): 580-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12447471

•

Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. Author(s): Paciocco G, Martinez FJ, Bossone E, Pielsticker E, Gillespie B, Rubenfire M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 April; 17(4): 647-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401059

•

Peripheral airway obstruction in primary pulmonary hypertension. Author(s): Meyer FJ, Ewert R, Hoeper MM, Olschewski H, Behr J, Winkler J, Wilkens H, Breuer C, Kubler W, Borst MM; German PPH Study Group. Source: Thorax. 2002 June; 57(6): 473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037220

•

Plasminogen activation by blood monocytes and alveolar macrophages in primary pulmonary hypertension. Author(s): Martin I, Humbert M, Marfaing-Koka A, Capron F, Wolf M, Meyer D, Simonneau G, Angles-Cano E. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 July; 13(5): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12138369

•

Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation. Author(s): Abramowicz MJ, Van Haecke P, Demedts M, Delcroix M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 September; 22(3): 560-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516151

Studies

61

•

Primary pulmonary hypertension and coronary artery bypass surgery. Author(s): Kuralay E, Demirkilic U, Oz BS, Cingoz F, Tatar H. Source: Journal of Cardiac Surgery. 2002 January-February; 17(1): 79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12027132

•

Primary pulmonary hypertension in pregnancy. Author(s): Vonk Noordegraaf A, Roeleveld RJ. Source: British Journal of Anaesthesia. 2002 January; 88(1): 151; Author Reply 151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11881877

•

Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Author(s): Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Source: Circulation. 2002 April 9; 105(14): 1672-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940546

•

Primary pulmonary hypertension is predominantly a hereditary disease. Author(s): Grunig E, Mereles D, Arnold K, Benz A, Olschewski H, MiltenbergerMiltenyi G, Borst MM, Abushi A, Seeger W, Winkler J, Hoper MM, Bartram CR, Kubler W, Janssen B. Source: Chest. 2002 March; 121(3 Suppl): 81S-82S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893705

•

Primary pulmonary hypertension may be a heterogeneous disease with a second locus on chromosome 2q31. Author(s): Rindermann M, Grunig E, von Hippel A, Koehler R, Miltenberger-Miltenyi G, Mereles D, Arnold K, Pauciulo M, Nichols W, Olschewski H, Hoeper MM, Winkler J, Katus HA, Kubler W, Bartram CR, Janssen B. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2237-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821254

•

Primary pulmonary hypertension treated with short-term epoprostenol infusion. Author(s): Shiota Y, Mikawa Y, Arikita H, Nakashima T, Horita N, Hiyama J, Ono T, Yamakido M. Source: Intern Med. 2003 September; 42(9): 824-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14518669

62

Primary Pulmonary Hypertension

•

Primary pulmonary hypertension, Castleman's disease and human herpesvirus-8. Author(s): Bull TM, Cool CD, Serls AE, Rai PR, Parr J, Neid JM, Geraci MW, Campbell TB, Voelkel NF, Badesch DB. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 September; 22(3): 403-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516126

•

Primary pulmonary hypertension. Author(s): Steenhuis LH. Source: The Netherlands Journal of Medicine. 2002 April; 60(3): 133-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164370

•

Primary pulmonary hypertension. Author(s): Rashid A, Lehrman S, Romano P, Frishman W, Dobkin J, Reichel J. Source: Heart Disease. 2000 November-December; 2(6): 422-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728293

•

Primary pulmonary hypertension. Author(s): Runo JR, Loyd JE. Source: Lancet. 2003 May 3; 361(9368): 1533-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737878

•

Primary pulmonary hypertension: a review for advanced practice nurses. Author(s): Adiutori DM. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2000 October; 9(5): 255-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904905

•

Primary pulmonary hypertension: an overview of epidemiology and pathogenesis. Author(s): Ghamra ZW, Dweik RA. Source: Cleve Clin J Med. 2003 April; 70 Suppl 1: S2-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716137

•

Prognosis in patients with primary pulmonary hypertension awaiting lung transplantation. Author(s): Ewert R, Wensel R, Opitz C, Habedank D, Lodziewski S, Hummel M, Knosalla C, Kapell S, Dandel M, Hetzer R; Berlin Pulmonary Hypertension Group. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3574-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750520

Studies

63

•

Progress in, and future prospects for, the treatment of primary pulmonary hypertension. Author(s): Wilkins MR, Wharton J. Source: Heart (British Cardiac Society). 2001 December; 86(6): 603-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711446

•

Proximal pulmonary arterial and intrapulmonary radiologic features of Eisenmenger syndrome and primary pulmonary hypertension. Author(s): Perloff JK, Hart EM, Greaves SM, Miner PD, Child JS. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 182-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860221

•

Pulmonary arterial hypertension--the primary pulmonary hypertension syndromes. Author(s): Hey JC, Scharf SM. Source: Isr Med Assoc J. 2003 April; 5(4): 298-303. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509142

•

Pulmonary artery pressure-flow relations after prostacyclin in primary pulmonary hypertension. Author(s): Castelain V, Chemla D, Humbert M, Sitbon O, Simonneau G, Lecarpentier Y, Herve P. Source: American Journal of Respiratory and Critical Care Medicine. 2002 February 1; 165(3): 338-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11818317

•

Quantification of hemodynamics in primary pulmonary hypertension with magnetic resonance imaging. Author(s): Tardivon AA, Mousseaux E, Brenot F, Bittoun J, Jolivet O, Bourroul E, Duroux P. Source: American Journal of Respiratory and Critical Care Medicine. 1994 October; 150(4): 1075-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7921439

•

Quantitative analysis of lung perfusion in patients with primary pulmonary hypertension. Author(s): Fukuchi K, Hayashida K, Nakanishi N, Inubushi M, Kyotani S, Nagaya N, Ishida Y. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 June; 43(6): 757-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12050319

64

Primary Pulmonary Hypertension

•

Rapid regression of primary pulmonary hypertension. Author(s): McMahon CJ, Kadkin J, Nihill MR. Source: Heart (British Cardiac Society). 2001 July; 86(1): E1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11410578

•

Recovery from circulatory shock in severe primary pulmonary hypertension (PPH) with aerosolization of iloprost. Author(s): Olschewski H, Ghofrani HA, Walmrath D, Temmesfeld-Wollbruck B, Grimminger F, Seeger W. Source: Intensive Care Medicine. 1998 June; 24(6): 631-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9681789

•

Recovery of cardiac function after living-donor lung transplantation in a patient with primary pulmonary hypertension. Author(s): Kusano KF, Date H, Fujio H, Miyaji K, Matsubara H, Nagahiro I, Satoh T, Shimizu N, Ohe T. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 March; 66(3): 294-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11922281

•

Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. Author(s): McLaughlin VV, Genthner DE, Panella MM, Rich S. Source: The New England Journal of Medicine. 1998 January 29; 338(5): 273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9445406

•

Regional alterations in lung ventilation in end-stage primary pulmonary hypertension: correlation between CT and scintigraphy. Author(s): Engeler CE, Kuni CC, Tashjian JH, Engeler CM, du Cret RP. Source: Ajr. American Journal of Roentgenology. 1995 April; 164(4): 831-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7726033

•

Regression of primary pulmonary hypertension. Author(s): Arcangeli C, Pucci P, Montereggi A, Dolara A. Source: Chest. 1990 December; 98(6): 1547. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2245722

•

Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension. Author(s): Uren NG, Ludman PF, Crake T, Oakley CM. Source: Journal of the American College of Cardiology. 1992 March 15; 19(4): 835-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1372015

Studies

65

•

Responses to constant work rate bicycle ergometry exercise in primary pulmonary hypertension: the effect of inhaled nitric oxide. Author(s): Riley MS, Porszasz J, Engelen MP, Shapiro SM, Brundage BH, Wasserman K. Source: Journal of the American College of Cardiology. 2000 August; 36(2): 547-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933371

•

Reversal of nocturnal periodic breathing in primary pulmonary hypertension after lung transplantation. Author(s): Schulz R, Fegbeutel C, Olschewski H, Rose F, Schafers HJ, Seeger W. Source: Chest. 2004 January; 125(1): 344-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718466

•

Right ventricular phenotypic characteristics in subjects with primary pulmonary hypertension or idiopathic dilated cardiomyopathy. Author(s): Quaife RA, Lynch D, Badesch DB, Voelkel NF, Lowes BD, Robertson AD, Bristow MR. Source: Journal of Cardiac Failure. 1999 March; 5(1): 46-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10194660

•

Risk and benefit of lung biopsy in primary pulmonary hypertension. Author(s): Kay JM. Source: Circulation. 1990 June; 81(6): 2029-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2344692

•

Role of hemodynamics in pulmonary vascular remodeling: implications for primary pulmonary hypertension. Author(s): Botney MD. Source: American Journal of Respiratory and Critical Care Medicine. 1999 February; 159(2): 361-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9927344

•

Role of human immunodeficiency virus in primary pulmonary hypertension--case reports. Author(s): Pellicelli AM, Palmieri F, D'Ambrosio C, Rianda A, Boumis E, Girardi E, Antonucci G, D'Amato C, Borgia MC. Source: Angiology. 1998 December; 49(12): 1005-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9855375

•

Role of pharmacologic tests in the treatment of primary pulmonary hypertension. Author(s): Galie N, Ussia G, Passarelli P, Parlangeli R, Branzi A, Magnani B. Source: The American Journal of Cardiology. 1995 January 19; 75(3): 55A-62A. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7840056

66

Primary Pulmonary Hypertension

•

Role of prostacyclin in the treatment of primary pulmonary hypertension. Author(s): Cremona G, Higenbottam T. Source: The American Journal of Cardiology. 1995 January 19; 75(3): 67A-71A. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7840058

•

Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. Author(s): Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simonneau G, Dartevelle P, Hamon M, Adnot S. Source: The Journal of Clinical Investigation. 2001 October; 108(8): 1141-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11602621

•

Sildenafil for primary pulmonary hypertension: short and long-term symptomatic benefit. Author(s): Jackson G, Chambers J. Source: Int J Clin Pract. 2002 June; 56(5): 397-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137450

•

Sildenafil improves right-ventricular parameters and quality of life in primary pulmonary hypertension. Author(s): Zimmermann AT, Calvert AF, Veitch EM. Source: Internal Medicine Journal. 2002 August; 32(8): 424-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12162403

•

Sildenafil in primary pulmonary hypertension. Author(s): Prasad S, Wilkinson J, Gatzoulis MA. Source: The New England Journal of Medicine. 2000 November 2; 343(18): 1342. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11183578

•

Sildenafil in primary pulmonary hypertension--is there a subset of patients who respond favourably? Author(s): Sayin T, Zenci M. Source: The Canadian Journal of Cardiology. 2002 June; 18(6): 676-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12107425

•

Sildenafil treatment of primary pulmonary hypertension. Author(s): Laupland KB, Helmersen D, Zygun DA, Viner SM. Source: Can Respir J. 2003 January-February; 10(1): 48-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624621

Studies

67

•

Specific bone morphogenic protein receptor II mutations found in primary pulmonary hypertension cause different biochemical phenotypes in vitro. Author(s): Thomas AQ, Carneal J, Markin C, Lane KB, Phillips JA 3rd, Loyd JE, Gaddipati R. Source: Chest. 2002 March; 121(3 Suppl): 83S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893707

•

Spontaneous bacterial peritonitis due to Listeria monocytogenes in a patient with primary pulmonary hypertension. Author(s): Rohde H, Horstkotte MA, Sobottka I, Klose H, Mack D. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 April; 21(4): 323-5. Epub 2002 April 13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072948

•

Stenting to reverse left ventricular ischemia due to left main coronary artery compression in primary pulmonary hypertension. Author(s): Rich S, McLaughlin VV, O'Neill W. Source: Chest. 2001 October; 120(4): 1412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591592

•

Survival and prognostic factors in patients with primary pulmonary hypertension. Author(s): Chun KJ, Kim SH, An BJ, Kim SH, Ha JK, Hong TJ, Shin YW. Source: Korean J Intern Med. 2001 June; 16(2): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590905

•

The age-adjusted mortality rate from primary pulmonary hypertension, in age range 20 to 54 years, did not increase during the years of peak “phen/fen” use. Author(s): Rothman RB. Source: Chest. 2000 November; 118(5): 1516-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11083718

•

The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. Author(s): Rich S, McLaughlin VV. Source: Journal of the American College of Cardiology. 1999 October; 34(4): 1184-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10520810

•

The enigma of primary pulmonary hypertension. Author(s): Krohn BG. Source: Journal of the American College of Cardiology. 2001 April; 37(5): 1476-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300467

68

Primary Pulmonary Hypertension

•

The prognostic role of the ECG in primary pulmonary hypertension. Author(s): Bossone E, Paciocco G, Iarussi D, Agretto A, Iacono A, Gillespie BW, Rubenfire M. Source: Chest. 2002 February; 121(2): 513-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834666

•

Therapy for primary pulmonary hypertension. Author(s): McCormack D. Source: Can Respir J. 2003 April; 10(3): 169-70. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12712230

•

Thyroid disease and primary pulmonary hypertension. Author(s): Kashyap AS, Kashyap S. Source: Jama : the Journal of the American Medical Association. 2001 June 13; 285(22): 2853-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401596

•

Treatment of primary pulmonary hypertension -- the next generation. Author(s): Newman JH. Source: The New England Journal of Medicine. 2002 March 21; 346(12): 933-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907295

•

Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension. Author(s): Ziesche R, Petkov V, Wittmann K, Kopatschka J, Stiebellehner L, Schenk P, Germann P, Roder G, Ullrich R, Block LH. Source: Heart (British Cardiac Society). 2000 April; 83(4): 406-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10722538

•

Twin pregnancy in a woman on long-term epoprostenol therapy for primary pulmonary hypertension. A case report. Author(s): Badalian SS, Silverman RK, Aubry RH, Longo J. Source: J Reprod Med. 2000 February; 45(2): 149-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710749

•

Two cases of primary pulmonary hypertension diagnosed during pregnancy. Author(s): Takeuchi K, Yokota H, Moriyama T, Ideta K, Maruo T. Source: Journal of Perinatal Medicine. 1998; 26(3): 248-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773389

Studies

69

•

Understanding primary pulmonary hypertension. Author(s): Berkowitz DS, Coyne NG. Source: Critical Care Nursing Quarterly. 2003 January-March; 26(1): 28-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12669944

•

Understanding right and left ventricular systolic function and interactions at rest and with exercise in primary pulmonary hypertension. Author(s): Nootens M, Wolfkiel CJ, Chomka EV, Rich S. Source: The American Journal of Cardiology. 1995 February 15; 75(5): 374-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7856531

•

Unpredictable response to vasodilator therapy in primary pulmonary hypertension. Author(s): Schmiedt MI, Shettigar UR, Siddique M, Barbier G, Bialow M, Carranza S. Source: Int J Clin Pharmacol Ther. 1998 August; 36(8): 435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9726697

•

Urinary cGMP concentrations in severe primary pulmonary hypertension. Author(s): Bogdan M, Humbert M, Francoual J, Claise C, Duroux P, Simonneau G, Lindenbaum A. Source: Thorax. 1998 December; 53(12): 1059-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10195079

•

Use of epoprostenol (Flolan) in the management of primary pulmonary hypertension. Author(s): Kayser SR. Source: Progress in Cardiovascular Nursing. 1998 Summer; 13(3): 39-41, 45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9950022

•

Use of inhaled nitric oxide for emergency Cesarean section in a woman with unexpected primary pulmonary hypertension. Author(s): Decoene C, Bourzoufi K, Moreau D, Narducci F, Crepin F, Krivosic-Horber R. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2001 June; 48(6): 584-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11444454

•

Use of stellate ganglion blocks for chronic chest pain associated with primary pulmonary hypertension. Author(s): Parris WC, Lin S, Frist W Jr. Source: Anesthesia and Analgesia. 1988 October; 67(10): 993-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3421503

70

Primary Pulmonary Hypertension

•

Usefulness of atrial septostomy as a treatment for primary pulmonary hypertension and guidelines for its application. Author(s): Rich S, Dodin E, McLaughlin VV. Source: The American Journal of Cardiology. 1997 August 1; 80(3): 369-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9264443

•

Uveal effusion and angle-closure glaucoma in primary pulmonary hypertension. Author(s): Krohn J, Bjune C. Source: American Journal of Ophthalmology. 2003 May; 135(5): 705-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719080

•

Uveal effusion syndrome associated with primary pulmonary hypertension and vomiting. Author(s): Akduman L, Del Priore LV, Kaplan HJ, Meredith T. Source: American Journal of Ophthalmology. 1996 May; 121(5): 578-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8610808

•

Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Author(s): Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon MD, Seward JB. Source: The American Journal of Cardiology. 1998 May 1; 81(9): 1157-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9605059

•

Vascular smooth muscle cell phenotypes in primary pulmonary hypertension. Author(s): Mitani Y, Ueda M, Komatsu R, Maruyama K, Nagai R, Matsumura M, Sakurai M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 February; 17(2): 316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11334137

•

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. Author(s): Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, Block LH. Source: The Journal of Clinical Investigation. 2003 May; 111(9): 1339-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727925

•

Vasodilator therapy for primary pulmonary hypertension in children. Author(s): Barst RJ, Maislin G, Fishman AP. Source: Circulation. 1999 March 9; 99(9): 1197-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10069788

Studies

71

•

Vasodilator treatment of primary pulmonary hypertension. Author(s): Cotter L. Source: Advances in Experimental Medicine and Biology. 1984; 164: 359-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6695579

•

Vasodilators and primary pulmonary hypertension. Variability of long-term response. Author(s): Dantzker DR, D'Alonzo GE, Gianotti L, Fuentes F, Nickeson D, Emerson M. Source: Chest. 1989 June; 95(6): 1185-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2721250

•

Vasodilators in primary pulmonary hypertension: an old dilemma revisited. Author(s): Mangieri E, Puddu E, Martuscelli E, Lanti M, Danesi A, Nigri A, Reale A. Source: Cardiologia. 1987 February; 32(2): 131-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3594494

•

Vasodilators in the treatment of primary pulmonary hypertension. Author(s): Weir EK, Schremmer B. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 August; 12(2): 263-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9727771

•

Ventilation-perfusion inequalities during graft rejection in patients undergoing single lung transplantation for primary pulmonary hypertension. Author(s): Levine SM, Jenkinson SG, Bryan CL, Anzueto A, Zamora CA, Gibbons WJ, Calhoon JH, Trinkle JK. Source: Chest. 1992 February; 101(2): 401-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1735262

•

Ventilation-perfusion inequalities in a patient with obliterative bronchiolitis after single-lung transplantation for primary pulmonary hypertension. Author(s): Mannes GP, de Boer WJ, Meuzelaar JJ, Meinesz AF. Source: Chest. 1993 April; 103(4): 1311. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8131508

73

CHAPTER 2. NUTRITION AND PRIMARY PULMONARY HYPERTENSION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and primary pulmonary hypertension.

Finding Nutrition Studies on Primary Pulmonary Hypertension The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “primary pulmonary hypertension” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

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

74

Primary Pulmonary Hypertension

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

Acute hemodynamic response to vasodilators in primary pulmonary hypertension. Author(s): Dept. of Cardiology, KEM Hospital, Parel, Mumbai. Source: Kulkarni, H Srinivas, A Vora, A Kerkar, P Dalvi, B J-Postgrad-Med. 1996 JanMarch; 42(1): 7-11 0022-3859

•

Aerosolised iloprost improves pulmonary haemodynamics in patients with primary pulmonary hypertension receiving continuous epoprostenol treatment. Author(s): University of Vienna Medical School, Department of Internal Medicine, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. Source: Petkov, V Ziesche, R Mosgoeller, W Schenk, P Vonbank, K Stiebellehner, L Raderer, M Brunner, C Kneussl, M Block, L H Thorax. 2001 September; 56(9): 734-6 00406376

•

Anaesthetic management for laparoscopic sterilisation and termination of pregnancy in a patient with severe primary pulmonary hypertension. Author(s): Department of Anaesthesia, Alfred Hospital, Melbourne, Victoria. Source: Myles, P S Anaesth-Intensive-Care. 1994 August; 22(4): 465-9 0310-057X

•

Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension: response to iloprost inhalation. Author(s): Department of Internal Medicine II, Justus-Liebig-University, Giessen, Germany. Source: Wiedemann, R Ghofrani, H A Weissmann, N Schermuly, R Quanz, K Grimminger, F Seeger, W Olschewski, H J-Am-Coll-Cardiol. 2001 October; 38(4): 1130-6 0735-1097

•

Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Author(s): Medizinische Klinik und Poliklinik, Innere Medizin V, Innere Medizin III, Homburg/Saar, Germany. [email protected] Source: Wilkens, H Guth, A Konig, J Forestier, N Cremers, B Hennen, B Bohm, M Sybrecht, G W Circulation. 2001 September 11; 104(11): 1218-22 1524-4539

•

Effects of a combination therapy of anticoagulant and vasodilator on the long-term prognosis of primary pulmonary hypertension. Author(s): First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. Source: Ogata, M Ohe, M Shirato, K Takishima, T Jpn-Circ-J. 1993 January; 57(1): 63-9 0047-1828

•

Long term inhalation of iloprost in a child with primary pulmonary hypertension: an alternative to continuous infusion. Author(s): Cardiology Unit, Hopital des Enfants, Department of Paediatrics, University Hospital of Geneva, 1211 Geneve 14, Switzerland. [email protected] Source: Beghetti, M Berner, M Rimensberger, P C Heart. 2001 September; 86(3): E10 1468-201X

•

Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. Author(s): Service de Pneumologie et Reanimation, UPRES EA 2705 on Pulmonary Vascular Diseases, Hopital Antoine Beclere, Universite Paris-Sud, Clamart, France. [email protected]

Nutrition

75

Source: Sitbon, O Humbert, M Nunes, H Parent, F Garcia, G Herve, P Rainisio, M Simonneau, G J-Am-Coll-Cardiol. 2002 August 21; 40(4): 780-8 0735-1097 •

Plasma brain natriuretic peptide as a parameter to assess efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) to treat severe primary pulmonary hypertension: a case report. Author(s): Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Japan. Source: Wakaumi, M Shiga, T Nozaki, K Fujiu, K Shimaya, K Ishizuka, N Matsuda, N Kasanuki, H Heart-Vessels. 2000; 15(3): 144-6 0910-8327

•

Primary pulmonary hypertension. World Health Organization. Source: Fauzi, A R Med-J-Malaysia. 2000 December; 55(4): 529-37; quiz 538 0300-5283

•

Prostacyclin in primary pulmonary hypertension. Author(s): Institute of Cardiology, University of Bologna, Italy. Source: Magnani, B Galie, N Eur-Heart-J. 1996 January; 17(1): 18-24 0195-668X

•

Prostacycline (Flolan). Intravenous nursing responsibilities in the care of the patient with primary pulmonary hypertension. Author(s): Intravenous Nurses Society, Cambridge, MA, USA. Source: Benvenuto, D B J-Intraven-Nurs. 1999 Sep-October; 22(5): 267-72 0896-5846

•

Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature. Author(s): Service of Internal Medicine, Hospital Mutua de Terrassa, University of Barcelona, Catalonia, Spain. [email protected] Source: Almagro, P Julia, J Sanjaume, M Gonzalez, G Casalots, J Heredia, J L Martinez, J Garau, J Medicine-(Baltimore). 2002 November; 81(6): 417-24 0025-7974

•

Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Author(s): Department of Paediatric Cardiology, Royal Brompton & Harefield NHS Trust, Sydney Street, London SW3 6NP, UK. Source: Abrams, D Schulze Neick, I Magee, A G Heart. 2000 August; 84(2): E4 1468-201X

•

Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Author(s): Rush-Presbyterian-St Luke's Medical Center, Department of Medicine, Section of Cardiology, Chicago, Ill 60612, USA. [email protected] Source: McLaughlin, V V Shillington, A Rich, S Circulation. 2002 September 17; 106(12): 1477-82 1524-4539

•

The influence of continuous intravenous prostacyclin therapy for primary pulmonary hypertension on the timing and outcome of transplantation. Author(s): Department of Surgery, The University of Maryland School of Medicine, Baltimore 21201, USA. Source: Conte, J V Gaine, S P Orens, J B Harris, T Rubin, L J J-Heart-Lung-Transplant. 1998 July; 17(7): 679-85 1053-2498

76

Primary Pulmonary Hypertension

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.healthnotes.com/

•

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

•

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

•

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

•

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

77

CHAPTER 3. CLINICAL TRIALS AND PRIMARY PULMONARY HYPERTENSION Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning primary pulmonary hypertension.

Recent Trials on Primary Pulmonary Hypertension The following is a list of recent trials dedicated to primary pulmonary hypertension.8 Further information on a trial is available at the Web site indicated. •

Phase III Randomized Study of UT-15 in Patients with Primary Pulmonary Hypertension Condition(s): Pulmonary Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; United Therapeutics Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of UT-15 in patients with severe symptomatic primary pulmonary hypertension. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004497

•

Phase IV Study of Chronic Infusional Epoprostenol for Severe Primary Pulmonary Hypertension Condition(s): Hypertension, Pulmonary Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Baylor College of Medicine

8

These are listed at www.ClinicalTrials.gov.

78

Primary Pulmonary Hypertension

Purpose - Excerpt: Objectives: I. Provide epoprostenol (Flolan, prostaglandin I2) by chronic infusion to patients with severe primary pulmonary hypertension for whom no alternative therapy is available. II. Obtain additional safety information on continuous infusion epoprostenol. III. Obtain additional information on economic resource health consumption. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004754

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “primary pulmonary hypertension” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Clinical Trials 79

•

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

•

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

•

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

•

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

•

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

•

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

81

CHAPTER 4. PATENTS HYPERTENSION

ON

PRIMARY

PULMONARY

Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “primary pulmonary hypertension” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on primary pulmonary hypertension, we have not necessarily excluded non-medical patents in this bibliography.

Patent Applications on Primary Pulmonary Hypertension As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to primary pulmonary hypertension: 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 10 This has been a common practice outside the United States prior to December 2000.

82

•

Primary Pulmonary Hypertension

Carbon monoxide as a biomarker and therapeutic agent Inventor(s): Choi, Augustine M.; (Guilford, CT), Lee, Patty J.; (Guilford, CT), Leo, Otterbein E.; (Hamden, CT) Correspondence: Janis K. Fraser, PH.D., J.D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020155166 Date filed: January 15, 2002 Abstract: The present invention relates to the use of carbon monoxide (CO) as a biomarker and therapeutic agent of heart, lung, liver, spleen, brain, skin and kidney diseases and other conditions and disease states including, for example, asthma, emphysema, bronchitis, adult respiratory distress syndrome, sepsis, cystic fibrosis, pneumonia, interstitial lung diseases, idiopathic pulmonary diseases, other lung diseases including primary pulmonary hypertension, secondary pulmonary hypertension, cancers, including lung, larynx and throat cancer, arthritis, wound healing, Parkinson's disease, Alzheimer's disease, peripheral vascular disease and pulmonary vascular thrombotic diseases such as pulmonary embolism. CO may be used to provide anti-inflammatory relief in patients suffering from oxidative stress and other conditions especially including sepsis and septic shock. In addition, carbon monoxide may be used as a biomarker or therapeutic agent for reducing respiratory distress in lung transplant patients and to reduce or inhibit oxidative stress and inflammation in transplant patients. Excerpt(s): This application claims priority from provisional application No. 60/127,616, filed Apr. 1, 1999. Heme oxygenase (HO) catalyzes the first and rate limiting step in the degradation of heme to yield equimolar quantities of biliverdin IXa, carbon monoxide (CO), and iron (Choi, et al., Am. J. Respir. Cell Mol. Biol. 15: 9-19; and Maines, Annu. Rev. Pharmacol. Toxicol. 37: 517-554). Three isoforms of HO exist; HO-1 is highly inducible while HO-2 and HO-3 are constitutively expressed (Choi, et al., supra, Maines, supra and McCoubrey, et al., E. J. Bioch. 247: 725-732). Although heme is the major substrate of HO-1, a variety of non-heme agents including heavy metals, cytokines, hormones, endotoxin and heat shock are also strong inducers of HO-1 expression (Choi, et al., supra, Maines, supra and Tenhunen, et al., J. Lab. Clin. Med. 75: 410-421). This diversity of HO-1 inducers has provided further support for the speculation that HO-1, besides its role in heme degradation, may also play a vital function in maintaining cellular homeostasis. Furthermore, HO-1 is highly induced by a variety of agents causing oxidative stress including hydrogen peroxide, glutathione depletors, UV irradiation, endotoxin and hyperoxia (Choi, et al., supra, Maines, supra and Keyse, et al., Proc. Natl. Acad. Sci. USA. 86: 99-103). One interpretation of this finding is that HO-1 can serve as a key biological molecule in the adaptation and/or defense against oxidative stress (Choi, et al., supra, Lee, et al., Proc Natl Acad Sci USA 93: 10393-10398; Otterbein, et al., Am. J. J. Respir. Cell Mol. Biol. 13: 595-601; Poss, et al., Proc. Natl. Acad. Sci. USA. 94: 10925-10930; Vile, et al., Proc. Natl. Acad. Sci. 91: 2607-2610; Abraham, et al., Proc. Natl. Acad. Sci. USA. 92: 6798-6802; and Vile and Tyrrell, J. Biol. Chem. 268: 14678-14681. Our laboratory and others have shown that induction of endogenous HO-1 provides protection both in vivo and in vitro against oxidative stress associated with hyperoxia and lipopolysaccharide-induced tissue injury (Lee, et al., supra, Otterbein, et al., supra and Taylor, et al., Am. J Physiol. 18: L582-L591). We have also shown that exogenous administration of HO-1 via gene transfer can provide protection against oxidant tissue injury and elicit tolerance to hyperoxic stress (Otterbein, et al., Am. J. Resp. Crit. Care Med. 157: A565 (Abstr)).

Patents 83

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of diagnosing pulmonary hypertension Inventor(s): Foroud, Tatiana; (Indianapolis, IN), Lane, Kirk B.; (Brentwood, TN), Loyd, James E.; (Nashville, TN), Machado, Rajiv D.; (Leicester, GB), Nichols, William C.; (Loveland, OH), Pauciulo, Michael W.; (Blue Ash, OH), Phillips, John A. III; (Brentwood, TN), Thomson, Jennifer R.; (Leeds, GB), Trembath, Richard C.; (Rutland, GB) Correspondence: Needle & Rosenberg, P.C.; The Candler Building, Suite 1200; 127 Peachtree Street, N.E.; Atlanta; GA; 30303-1811; US Patent Application Number: 20020102576 Date filed: July 17, 2001 Abstract: This invention relates generally to a method of identifying an individual having an increased susceptibility to developing Familial Primary Pulmonary Hypertension (FPPH), as well as to a method for diagnosing an individual suffering from FPPH. The invention also relates to a method of identifying an individual having an increased susceptibility to developing (non-familial) Primary Pulmonary Hypertension (PPH), as well as to a method for diagnosing an individual suffering from PPH. Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/218,740, filed Jul. 17, 2000, and U.S. Provisional Application No. 60/220,133, filed Jul. 21, 2000. Application Ser. No. 60/218,740, filed Jul. 17, 2000, and U.S. Provisional Application No. 60/220,133, filed Jul. 21, 2000, are hereby incorporated herein by reference. Primary pulmonary hypertension (PH) is characterized by sustained elevation of pulmonary artery pressure (greater than 25 mmHg at rest and greater than 30 mmHg during exercise) and with no identifiable cause, such as recurrent thromboembolism, chronic hypoxic lung disease or left-sided cardiac disease. PPH is twice as common in females than males and symptoms develop typically in the 3.sup.rd and 4.sup.th decades of life, although the disease may occur at any age. Despite advances in therapy, mortality in PPH remains high with mean survival from onset of disease only 2.5 year. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Preventives and remedies for pulmonary hypertension Inventor(s): Egashira, Kensuke; (Fukuoka, JP), Ikeda, Yasuhiro; (Fukuoka, JP), Inada, Yoshiyuki; (Hyogo, JP), Sueishi, Katsuo; (Fukuoka, JP), Yonemitsu, Yoshikazu; (Fukuoka, JP) Correspondence: Takeda Pharmaceuticals North America, Inc; Intellectual Property Department; 475 Half Day Road; Suite 500; Lincolnshire; IL; 60069; US Patent Application Number: 20030162737 Date filed: March 22, 2003 Abstract: The present invention provides a prophylactic and/or therapeutic agent for pulmonary hypertension, comprising an antagonistic mutein of MCP-1 or a salt thereof, a DNA molecule comprising a nucleotide sequence encoding the antagonistic mutein of MCP-1, or a neutralizing antibody against MCP-1.The antagonistic mutein of MCP-1 or a salt thereof, the DNA molecule having a nucleotide sequence encoding the

84

Primary Pulmonary Hypertension

antagonistic mutein of MCP-1, or the neutralizing antibody against MCP-1 has hypotensive activity, and thus is useful as a pharmaceutical agent for preventing and/or treating pulmonary hypertension (primary pulmonary hypertension, in particular). Excerpt(s): The present invention relates to novel prophylactic and/or therapeutic agents for pulmonary hypertension. MPC-1 (Monocyte chemoattractant protein-1: macrophage chemotactic factor) is a member of the C--C chemokine family and is known to be highly expressed in the arteriosclerotic (e.g. atherosclerotic) lesion (Takeya, M. et al., Hum. Pathol. 24: 534-539 (1993); Yla-Herttuala, S. et al., Proc. Natl. Acad. Sci. USA, 88: 5252-5257 (1991)). On the other hand, primary pulmonary hypertension (PH) is a disease with poor prognosis, and heart-lung transplantation is the only therapy for this disease at present. However, heart-lung transplantation has considerable difficulty being used as a practical treatment due to the limited supply of donors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Role of PPH1 gene in pulmonary hypertension Inventor(s): Knowles, James A.; (Rowaytn, CT), Morse, Jane H.; (Bronx, NY) Correspondence: John P. White; Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20020022229 Date filed: July 12, 2001 Abstract: This invention provides a method of detecting whether a subject is either predisposed to or afflicted with a pulmonary disease which comprises (1) obtaining a suitable sample from the subject; (2) detecting in the sample a bone morphogenetic protein receptor-II mutation which is not present in wildtype bone morphogenetic protein receptor-II, wherein the presence of a mutation indicates that the subject is predisposed to or afflicted with the pulmonary disease. In one embodiment, the pulmonary disease is Familial Primary Pulmonary Hypertension. Excerpt(s): This application is a continuation-in-part and claims the benefit of U.S. Provisional Application No. 60/217,773, filed Jul. 12, 2000, the contents of which are hereby incorporated by reference into this application. The invention disclosed herein was made with Government support under NIH Grant No. HL60056-02 from the National Heart, Lung and Blood Institute. Accordingly, the government has certain rights in this invention. Throughout this application, various publications are referenced within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citations for these references may be found immediately preceding the claims. 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 primary pulmonary hypertension, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents,

Patents 85

perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “primary pulmonary hypertension” (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 primary pulmonary hypertension. You can also use this procedure to view pending patent applications concerning primary pulmonary hypertension. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

87

CHAPTER 5. PERIODICALS AND NEWS ON PRIMARY PULMONARY HYPERTENSION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover primary pulmonary hypertension.

News Services and Press Releases One of the simplest ways of tracking press releases on primary pulmonary hypertension is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “primary pulmonary hypertension” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to primary pulmonary hypertension. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “primary pulmonary hypertension” (or synonyms). The following was recently listed in this archive for primary pulmonary hypertension: •

Multiple agents helpful in primary pulmonary hypertension Source: Reuters Industry Breifing Date: March 12, 2004

88

Primary Pulmonary Hypertension

•

Epoprostenol lowers pulmonary vascular resistance in primary pulmonary hypertension Source: Reuters Industry Breifing Date: February 23, 2004

•

HHV-8 may play role in primary pulmonary hypertension Source: Reuters Medical News Date: September 17, 2003

•

Vasoactive intestinal peptide may be effective against primary pulmonary hypertension Source: Reuters Medical News Date: May 15, 2003

•

Epoprostenol improves long-term survival of primary pulmonary hypertension Source: Reuters Industry Breifing Date: August 26, 2002

•

Serotonin transporter key in pathogenesis of primary pulmonary hypertension Source: Reuters Medical News Date: October 31, 2001

•

Genetic basis of primary pulmonary hypertension clarified Source: Reuters Medical News Date: August 01, 2001

•

Gene responsible for many cases of familial primary pulmonary hypertension identified Source: Reuters Industry Breifing Date: July 24, 2000

•

Long-term iloprost aerosol therapy effective in primary pulmonary hypertension Source: Reuters Industry Breifing Date: June 22, 2000

•

Fenfluramine use linked to increased risk of primary pulmonary hypertension Source: Reuters Medical News Date: March 13, 2000

•

Noninvasive predictor of hemodynamic status in patients with primary pulmonary hypertension identified Source: Reuters Medical News Date: January 14, 1999

•

Digoxin potentially useful in patients with primary pulmonary hypertension Source: Reuters Medical News Date: October 06, 1998

•

Epoprostenol Improves Survival And QOL In Patients With Primary Pulmonary Hypertension Source: Reuters Medical News Date: August 01, 1997

•

Gene For Familial Primary Pulmonary Hypertension Localized Source: Reuters Medical News Date: March 03, 1997

Periodicals and News

•

Primary Pulmonary Hypertension In HIV: The Influence Of HLA Class II Alleles Source: Reuters Medical News Date: April 16, 1996

•

Prostacyclin Improves Survival In Patients With Primary Pulmonary Hypertension Source: Reuters Medical News Date: February 01, 1996

•

Lancing The Atrial Septum Prolongs Survival In Patients With Primary Pulmonary Hypertension Source: Reuters Medical News Date: April 14, 1995

89

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “primary pulmonary hypertension” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “primary pulmonary hypertension” (or synonyms). If you know the name of a company that is relevant to primary pulmonary hypertension, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

90

Primary Pulmonary Hypertension

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “primary pulmonary hypertension” (or synonyms).

Academic Periodicals covering Primary Pulmonary Hypertension Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to primary pulmonary hypertension. In addition to these sources, you can search for articles covering primary pulmonary hypertension that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

91

CHAPTER 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for primary pulmonary hypertension. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with primary pulmonary hypertension. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-

92

Primary Pulmonary Hypertension

interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to primary pulmonary hypertension: Amphetamines •

Systemic - U.S. Brands: Adderall; Desoxyn; Desoxyn Gradumet; Dexedrine; Dexedrine Spansule; DextroStat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202031.html

Anticoagulants •

Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202050.html

Epoprostenol •

Systemic - U.S. Brands: Flolan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203429.html

Heparin •

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

Hydralazine and Hydrochlorothiazide •

Systemic - U.S. Brands: Apresazide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202286.html

Isoniazid •

Systemic - U.S. Brands: Laniazid; Nydrazid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202307.html

Phenoxybenzamine •

Systemic - U.S. Brands: Dibenzyline http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202458.html

Phentolamine and Papaverine •

Intracavernosal - U.S. Brands: Regitine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202459.html

Prazosin •

Systemic - U.S. Brands: Minipress http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202475.html

Prazosin and Polythiazide •

Systemic - U.S. Brands: Minizide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202476.html

Procainamide •

Systemic - U.S. Brands: Promine; Pronestyl; Pronestyl-SR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202483.html

Researching Medications

93

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to primary pulmonary hypertension by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “primary pulmonary hypertension” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing

94

Primary Pulmonary Hypertension

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 may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for primary pulmonary hypertension: •

Epoprostenol (trade name: Flolan) http://www.rarediseases.org/nord/search/nodd_full?code=410

•

15AU81 http://www.rarediseases.org/nord/search/nodd_full?code=871

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

95

APPENDICES

97

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

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

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

•

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

•

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

•

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

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

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

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

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

11

These publications are typically written by one or more of the various NIH Institutes.

98

Primary Pulmonary Hypertension

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

99

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

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

100

Primary Pulmonary Hypertension

•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “primary pulmonary hypertension” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 2914 8 938 9 120 3989

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

14

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

15

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

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

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

Physician Resources

101

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

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

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

•

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

19 Adapted 20

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

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

103

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on primary pulmonary hypertension can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to primary pulmonary hypertension. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to primary pulmonary hypertension. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “primary pulmonary hypertension”:

104

Primary Pulmonary Hypertension

Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html Circulatory Disorders http://www.nlm.nih.gov/medlineplus/circulatorydisorders.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html COPD http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.t ml Health Occupations http://www.nlm.nih.gov/medlineplus/healthoccupations.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Immune System and Disorders http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html Pulmonary Fibrosis http://www.nlm.nih.gov/medlineplus/pulmonaryfibrosis.html Pulmonary Hypertension http://www.nlm.nih.gov/medlineplus/pulmonaryhypertension.html Refractive Errors http://www.nlm.nih.gov/medlineplus/refractiveerrors.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html

Within the health topic page dedicated to primary pulmonary hypertension, the following was listed: •

General/Overviews Primary Pulmonary Hypertension (PPH) Source: American Lung Association http://www.lungusa.org/diseases/pphfac.html Pulmonary Hypertension http://circ.ahajournals.org/cgi/reprint/106/24/e192.pdf

•

Diagnosis/Symptoms Echocardiogram Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/echocardiogram.pdf Understanding PFT's (Pulmonary Function Testing) Source: Alpha 1 Association http://www.alpha1.org/what/lunginfo_pfts.htm

Patient Resources

•

105

Specific Conditions/Aspects Primary or Unexplained Pulmonary Hypertension Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4752

•

Children Persistent Pulmonary Hypertension of the Newborn (PPHN) Source: Nemours Foundation http://kidshealth.org/parent/medical/heart/pphn.html

•

From the National Institutes of Health Primary Pulmonary Hypertension Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/pph_doc.htm

•

Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 American Lung Association http://www.lungusa.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/

•

Statistics Pulmonary Hypertension Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/cvh/library/fs_pulmonary_hypertension.htm

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to primary pulmonary hypertension. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore,

106

Primary Pulmonary Hypertension

for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to primary pulmonary hypertension. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with primary pulmonary hypertension. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about primary pulmonary hypertension. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “primary pulmonary hypertension” (or a synonym), and you will receive information on all relevant organizations listed in the database.

Patient Resources

107

Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “primary pulmonary hypertension”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “primary pulmonary hypertension” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “primary pulmonary hypertension” (or a synonym) into the search box, and click “Submit Query.”

109

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

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

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

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

22

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

110

Primary Pulmonary Hypertension

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

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

23

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

Finding Medical Libraries 111

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

112

Primary Pulmonary Hypertension

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries 113

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

114

Primary Pulmonary Hypertension

•

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

•

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

•

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

•

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

115

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Primary Pulmonary Hypertension Primary pulmonary hypertension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000112.htm Pulmonary hypertension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000112.htm

•

Signs & Symptoms for Primary Pulmonary Hypertension Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Coughing up blood Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003073.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm

116

Primary Pulmonary Hypertension

Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Hyperactivity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003256.htm Hyperventilation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Lightheadedness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Primary Pulmonary Hypertension ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Angiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Arteriogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Blood gases Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003855.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Cardiac catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003419.htm

Online Glossaries 117

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 ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Heart catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003419.htm Lung scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003824.htm Pulmonary arteriogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003813.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 Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm Right heart catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003870.htm V/Q scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003828.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Surgery and Procedures for Primary Pulmonary Hypertension Heart-lung transplantation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003004.htm Lung transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003010.htm

•

Background Topics for Primary Pulmonary Hypertension Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm

118

Primary Pulmonary Hypertension

Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm

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

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

•

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

•

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

•

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

119

PRIMARY PULMONARY HYPERTENSION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 4-Aminopyridine: A potassium channel blocker. It is used primarily as a research tool and is helpful in characterizing subtypes of potassium channels. It has been used clinically in Lambert-Eaton syndrome and multiple sclerosis because by blocking potassium channels it prolongs action potentials thereby increasing transmitter release at the neuromuscular junction (and elsewhere). [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar

120

Primary Pulmonary Hypertension

tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH]

Dictionary 121

Allogeneic: Taken from different individuals of the same species. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory

122

Primary Pulmonary Hypertension

and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexiant: A drug, process, or event that leads to anorexia. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Apoptosis: One of the two mechanisms by which cell pathological process of necrosis). Apoptosis is the physiological deletion of cells and appears to be characterized by distinctive morphologic changes in the

death occurs (the other being the mechanism responsible for the intrinsically programmed. It is nucleus and cytoplasm, chromatin

Dictionary 123

cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Armadillos: Burrowing, chiefly nocturnal mammals of the family Dasypodidae having bodies and heads encased in small bony plates. They are widely distributed in the warmer parts of the Americas. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriogram: An x-ray of arteries; the person receives an injection of a dye that outlines the vessels on an x-ray. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or

124

Primary Pulmonary Hypertension

bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Balloon dilation: A treatment for benign prostatic hyperplasia or prostate enlargement. A tiny balloon is inflated inside the urethra to make it wider so urine can flow more freely from the bladder. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]

Dictionary 125

Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of

126

Primary Pulmonary Hypertension

osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capnography: Continuous recording of the carbon dioxide content of expired air. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual

Dictionary 127

patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for

128

Primary Pulmonary Hypertension

the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and

Dictionary 129

theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge.

130

Primary Pulmonary Hypertension

[NIH]

Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexfenfluramine: The S-isomer of fenfluramine. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the

Dictionary 131

background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH]

132

Primary Pulmonary Hypertension

Duct: A tube through which body fluids pass. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH]

Dictionary 133

Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] Ergometry: Any method of measuring the amount of work done by an organism, usually during exertion. Ergometry also includes measures of power. Some instruments used in these determinations include the hand crank and the bicycle ergometer. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

134

Primary Pulmonary Hypertension

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH]

Dictionary 135

Flatus: Gas passed through the rectum. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH] Gland: An organ that produces and releases one or more substances for use in the body.

136

Primary Pulmonary Hypertension

Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart Catheterization: Procedure which includes placement of catheter, recording of intracardiac and intravascular pressure, obtaining blood samples for chemical analysis, and cardiac output measurement, etc. Specific angiographic injection techniques are also involved. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue,

Dictionary 137

breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart-Lung Transplantation: The simultaneous, or near simultaneous, transference of heart and lungs from one human or animal to another. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird

138

Primary Pulmonary Hypertension

and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] 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] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU]

Dictionary 139

Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] 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] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH]

140

Primary Pulmonary Hypertension

Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin

Dictionary 141

or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Investigative Techniques: Investigative techniques used in pre-clinical and clinical research, epidemiology, chemistry, immunology, genetics, etc. They do not include techniques specifically applied to diagnosis; therapeutics; anesthesia and analgesia, surgery, operative, and dentistry. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to

142

Primary Pulmonary Hypertension

which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of

Dictionary 143

macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macrophage Inflammatory Protein-1: A chemokine that is chemotactic for neutrophils and monocytes, stimulates macrophages, and may play a role in regulating hematopoiesis. Its two variants, MIP-1alpha and MIP-1beta, are 60% homologous to each other. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH]

144

Primary Pulmonary Hypertension

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocrotaline: A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary

Dictionary 145

arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier

146

Primary Pulmonary Hypertension

nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear magnetic resonance imaging: NMRI. A procedure in which a magnet linked to a computer is used to create detailed pictures of areas inside the body. Also called magnetic resonance imaging (MRI). [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH]

Dictionary 147

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH]

Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH]

148

Primary Pulmonary Hypertension

Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perceived risk: Estimate or evaluation of risk as observed through personal experience or personal study, and personal evaluation of consequences. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardial Effusion: Presence of fluid within the pericardium. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Perivascular: Situated around a vessel. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove

Dictionary 149

dead cells. Phagocytes include macrophages. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phentermine: A central nervous system stimulant and sympathomimetic with actions and uses similar to those of dextroamphetamine. It has been used most frequently in the treatment of obesity. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH]

150

Primary Pulmonary Hypertension

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH]

Dictionary 151

Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or

152

Primary Pulmonary Hypertension

vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] 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]

Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an

Dictionary 153

antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes

154

Primary Pulmonary Hypertension

such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Vein: Central retinal vein and its tributaries. It runs a short course within the optic nerve and then leaves and empties into the superior ophthalmic vein or cavernous sinus. [NIH]

Retinal Vein Occlusion: Occlusion of the retinal vein. Those at high risk for this condition include patients with hypertension, diabetes mellitus, arteriosclerosis, and other cardiovascular diseases. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Root Planing: A procedure for smoothing of the roughened root surface or cementum of a tooth after subgingival curettage or scaling, as part of periodontal therapy. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH]

Dictionary 155

Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

156

Primary Pulmonary Hypertension

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH]

Dictionary 157

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] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Stellate Ganglion: A paravertebral sympathetic ganglion formed by the fusion of the inferior cervical and first thoracic ganglia. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and

158

Primary Pulmonary Hypertension

mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH]

Dictionary 159

Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] 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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH]

160

Primary Pulmonary Hypertension

Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new

Dictionary 161

blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Ventricular Pressure: The pressure within a cardiac ventricle. Ventricular pressure waveforms can be measured in the beating heart by catheterization or estimated using imaging techniques (e.g., Doppler echocardiography). The information is useful in evaluating the function of the myocardium, cardiac valves, and pericardium, particularly with simultaneous measurement of other (e.g., aortic or atrial) pressures. [NIH] Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and

162

Primary Pulmonary Hypertension

kill, tumor cells. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

163

INDEX 4 4-Aminopyridine, 23, 119 A Abdomen, 119, 125, 142, 157 Abdominal, 119, 125, 148 Abdominal Pain, 119, 148 Abscess, 119, 155 Acetylcholine, 64, 119, 145, 146 Acetylgalactosamine, 119, 136 Acetylglucosamine, 119, 136 Action Potentials, 119 Acute renal, 119, 137 Adaptability, 119, 127 Adaptation, 82, 119 Adenine, 119 Adenosine, 16, 119, 149, 158 Adenosine Triphosphate, 16, 119, 149 Adipose Tissue, 5, 119 Adjustment, 119, 120 Adverse Effect, 4, 120, 156 Aerobic, 120, 134, 144 Aerosol, 14, 88, 120 Affinity, 14, 41, 120, 156 Agar, 120, 149 Age Groups, 12, 120 Age of Onset, 120, 160 Age-Adjusted, 67, 120 Aged, 80 and Over, 120 Agonist, 120, 130 Airway, 11, 14, 60, 120, 151 Algorithms, 120, 124 Alkaline, 120, 126, 147 Alkaloid, 22, 120, 144, 158 Alleles, 12, 89, 120 Allogeneic, 121, 136 Alternative medicine, 89, 121 Alveoli, 121, 161 Ambulatory Care, 121 Amino acid, 121, 122, 123, 126, 131, 134, 138, 145, 148, 149, 150, 151, 155, 160 Amino Acid Sequence, 121, 122, 134 Anaesthesia, 29, 59, 61, 69, 74, 121, 139 Anal, 18, 121 Analog, 26, 39, 121, 139 Analogous, 121, 160 Anatomical, 121, 123, 127, 129, 131, 139 Anemia, 55, 121, 147 Anesthesia, 32, 56, 69, 120, 121, 141

Aneurysm, 34, 35, 54, 121, 161 Angina, 121, 146 Anginal, 121, 146 Angiogenesis, 11, 121 Animal model, 8, 19, 20, 24, 121 Anorexia, 121, 122 Anorexiant, 4, 122 Antagonism, 122, 131, 158 Antibacterial, 122, 157 Antibiotic, 122, 157, 158 Antibodies, 7, 122, 123, 136, 138, 142, 149 Antibody, 83, 120, 122, 136, 138, 139, 140, 141, 143, 144, 152, 153, 156, 162 Anticoagulant, 74, 122, 151 Antidepressant, 122, 135 Antigen, 120, 122, 138, 139, 140, 143 Antihypertensive, 122, 138, 146 Anti-infective, 122, 138 Anti-inflammatory, 82, 122 Antineoplastic, 122, 146 Antineoplastic Agents, 122, 146 Antioxidant, 122, 147 Anus, 121, 122, 125, 140 Aorta, 122, 129, 161 Aortic Valve, 56, 122 Apoptosis, 7, 8, 14, 15, 21, 56, 122 Aqueous, 123, 124, 130, 138, 142 Arachidonic Acid, 123, 132, 139, 141, 151 Arginine, 36, 51, 123, 146 Armadillos, 21, 123 Arrhythmia, 123, 161 Arterial, 7, 8, 12, 13, 15, 17, 18, 19, 23, 34, 63, 123, 138, 151, 158 Arteries, 9, 11, 20, 21, 24, 48, 50, 122, 123, 125, 129, 143, 145, 152, 159 Arteriogram, 116, 117, 123 Arterioles, 123, 125, 126, 161 Arteriosclerosis, 46, 123, 154 Arteriosus, 123, 152 Artery, 18, 36, 51, 63, 67, 121, 123, 129, 152 Asymptomatic, 28, 123 Atrial, 30, 31, 45, 70, 74, 89, 123, 161 Atrium, 123, 144, 161 Attenuation, 123, 144 Autoantibodies, 43, 123 Autoantigens, 123 Autoimmune disease, 22, 25, 123, 144 Autonomic, 119, 123

164

Primary Pulmonary Hypertension

B Bacteria, 122, 123, 124, 133, 143, 149, 155, 157, 159, 160 Bacterial Physiology, 119, 124 Bacteriophage, 124, 149, 160 Bacterium, 124, 137 Balloon dilation, 45, 124 Base, 119, 124, 130, 141, 158 Benign, 124, 135, 145, 152 Benign prostatic hyperplasia, 124 Bile, 124, 135, 142 Biochemical, 12, 25, 30, 67, 120, 124, 155 Biological therapy, 124, 136 Biomarkers, 17, 124 Biopsy, 32, 65, 116, 124 Biopsy specimen, 32, 124 Biotechnology, 26, 27, 89, 99, 124 Bladder, 124, 144, 151, 160 Blood Coagulation, 60, 124, 125, 126, 158 Blood Glucose, 125, 137, 140 Blood Platelets, 125, 155, 158 Blood pressure, 8, 19, 24, 116, 122, 125, 126, 138, 144, 146, 148, 150, 152, 156 Body Fluids, 124, 125, 132, 156, 160 Bone Marrow, 125, 135, 142, 144, 156 Bone scan, 125, 155 Bowel, 121, 125, 131, 148 Bowel Movement, 125, 131 Brachytherapy, 125, 140, 141, 152, 162 Bradykinin, 125, 146 Branch, 113, 125, 132, 142, 148, 156, 158 Breakdown, 125, 131, 135, 146 Bronchi, 125, 133, 158, 159 Bronchial, 125, 158 Bronchioles, 121, 125 Bronchiolitis, 71, 125 Bronchitis, 82, 125 Bronchopulmonary, 33, 125 C Caesarean section, 29, 125 Calcitonin, 64, 125, 126 Calcitonin Gene-Related Peptide, 64, 126 Calcium, 19, 46, 49, 125, 126, 131, 146, 156, 161 Calcium channel blocker, 126, 161 Callus, 126, 132 Capillary, 42, 53, 75, 125, 126, 161 Capnography, 56, 126 Carbon Dioxide, 126, 135, 153 Carcinogenic, 126, 140, 150 Carcinogens, 126, 147

Cardiac, 15, 18, 27, 33, 50, 51, 61, 63, 64, 65, 67, 68, 83, 116, 126, 133, 136, 145, 154, 161 Cardiac Output, 18, 67, 126, 136 Cardiomyopathy, 104, 126 Cardiopulmonary, 29, 33, 126, 144 Cardiovascular, 7, 17, 25, 39, 52, 69, 126, 134, 141, 154, 155 Cardiovascular disease, 126, 154 Carotene, 126, 154 Case report, 30, 35, 36, 65, 68, 75, 126, 127 Case series, 27, 127 Catecholamine, 127, 130, 149 Catheter, 18, 127, 136, 140 Catheterization, 19, 116, 117, 127, 140, 161 Cell Death, 7, 25, 122, 127 Cell Differentiation, 127, 156 Cell Division, 123, 127, 136, 144, 149, 151, 155 Cell membrane, 127, 130, 134, 162 Cell Physiology, 6, 127 Cell proliferation, 8, 9, 10, 20, 123, 127, 156 Cell Survival, 127, 136 Central Nervous System, 119, 127, 130, 135, 141, 144, 147, 149, 155, 158 Cerebrospinal, 127, 156 Cerebrospinal fluid, 127, 156 Cervical, 127, 157 Chest Pain, 69, 127 Chin, 127, 143 Cholesterol, 124, 128, 129 Chromatin, 26, 122, 128, 146 Chromosomal, 10, 128, 149, 154 Chromosome, 9, 13, 41, 43, 52, 54, 61, 128, 142, 155 Chronic, 6, 11, 20, 21, 25, 32, 33, 38, 58, 67, 69, 77, 78, 83, 105, 128, 140, 141, 155, 157 Cirrhosis, 128, 150 CIS, 26, 128, 154 Clamp, 19, 128 Clear cell carcinoma, 128, 130 Clinical Medicine, 48, 128, 150 Clinical Protocols, 19, 128 Clinical trial, 5, 24, 77, 78, 99, 128, 151, 153 Cloning, 124, 128 Coagulation, 124, 128, 137, 159 Collagen, 16, 121, 128, 134, 149, 150 Combination Therapy, 74, 128 Computational Biology, 99, 128 Computed tomography, 129, 155 Concomitant, 14, 129 Cones, 129, 154

Index 165

Conjugated, 129, 130 Connective Tissue, 125, 128, 129, 134, 135, 154, 155 Consciousness, 129, 131, 152, 153 Constipation, 129, 148 Constriction, 129, 141, 161 Constriction, Pathologic, 129, 161 Consumption, 18, 78, 129, 147 Contamination, 14, 129 Continuous infusion, 34, 74, 78, 129 Contraindications, ii, 129 Conus, 129, 152 Coronary, 5, 36, 51, 61, 67, 126, 129, 138, 143, 144, 146 Coronary Artery Bypass, 61, 129 Coronary heart disease, 5, 126, 129 Coronary Thrombosis, 129, 143, 145 Crossing-over, 129, 153 Curative, 129, 158 Curettage, 129, 154 Cyclic, 11, 130, 136, 146, 151, 158 Cystathionine beta-Synthase, 130, 138 Cytochrome, 25, 130 Cytokine, 10, 22, 130 Cytoplasm, 122, 127, 130, 136, 144, 146 Cytotoxic, 130, 152, 156 D Deletion, 122, 130 Density, 23, 130, 146 Depolarization, 9, 23, 130, 156 DES, 74, 130 Deuterium, 130, 138 Dexfenfluramine, 3, 31, 130 Dextroamphetamine, 130, 149 Diabetes Mellitus, 130, 137, 154 Diabetic Retinopathy, 11, 130 Diagnostic procedure, 81, 89, 131 Diastole, 131 Diastolic, 6, 70, 131, 138 Digestion, 124, 125, 131, 142, 157, 160 Digestive system, 79, 131 Dihydrotestosterone, 131, 153 Dilatation, 48, 121, 131, 161 Dilatation, Pathologic, 131, 161 Dilated cardiomyopathy, 65, 131 Dilation, 36, 125, 131, 161 Diltiazem, 58, 131 Dimethyl, 131, 146 Direct, iii, 13, 20, 24, 36, 91, 128, 131, 138, 153 Dissection, 28, 34, 131 Dissociation, 120, 131

Distal, 14, 129, 131, 152 Diuresis, 131, 158 Drug Interactions, 93, 131 Drug Tolerance, 131, 159 Duct, 127, 132, 154 Dyspnea, 9, 132 E Echocardiography, 33, 37, 43, 132, 161 Edema, 116, 131, 132 Effector, 6, 25, 119, 132 Efficacy, 4, 14, 18, 24, 28, 39, 75, 77, 132 Effusion, 70, 132 Eicosanoids, 20, 132 Elastic, 50, 132 Elastin, 128, 132 Electrolyte, 132, 150, 156 Electrophysiological, 132, 161 Embryo, 127, 132, 134, 139 Embryogenesis, 7, 132 Emphysema, 47, 82, 132 Encephalitis, 13, 132 Encephalitis, Viral, 132 Endemic, 132, 157 Endocrine Glands, 132 Endogenous, 17, 23, 82, 123, 126, 132, 147, 151, 160 Endothelial cell, 6, 10, 11, 13, 22, 25, 34, 56, 133, 158 Endothelium, 11, 20, 22, 49, 133, 146 Endothelium, Lymphatic, 133 Endothelium, Vascular, 133 Endothelium-derived, 133, 146 Endotoxin, 82, 133, 160 Environmental Health, 98, 100, 133 Enzymatic, 121, 126, 133, 154 Epidemic, 133, 157 Epidemiological, 16, 133 Epinephrine, 133, 145, 160 Epithelial, 10, 22, 133 Epithelial Cells, 22, 133 Epithelium, 11, 133 Epoprostenol, 17, 28, 34, 38, 39, 46, 50, 51, 53, 61, 64, 68, 69, 74, 75, 77, 78, 88, 92, 94, 133, 139 Ergometer, 133 Ergometry, 44, 65, 133 Erythrocytes, 121, 125, 133, 153 Esophageal, 40, 133 Esophagus, 131, 133, 157 Eukaryotic Cells, 134, 139, 147, 160 Evacuation, 36, 129, 134 Evoke, 134, 157

166

Primary Pulmonary Hypertension

Exercise Test, 29, 33, 134 Exocytosis, 25, 134 Exogenous, 82, 132, 134, 151, 160 Exon, 10, 134 External-beam radiation, 134, 141, 152, 162 Extracellular, 25, 129, 134, 156 Extracellular Matrix, 129, 134 F Family Planning, 99, 134 Fat, 119, 123, 125, 126, 129, 134, 142, 144, 154 Fatigue, 9, 116, 134, 136 Fatty acids, 132, 134, 151, 159 Fenfluramine, 3, 13, 23, 30, 31, 33, 88, 130, 134 Fetal Development, 21, 134 Fetus, 134 Fibrin, 124, 134, 148, 158, 159 Fibroblasts, 10, 22, 134, 140 Fibrosis, 82, 104, 134 Flatus, 135 Fluoxetine, 5, 135 Forearm, 125, 135 G Gallbladder, 119, 131, 135 Ganglia, 119, 135, 145, 157 Ganglion, 135, 147, 157 Gas, 21, 44, 126, 135, 138, 146, 161 Gas exchange, 21, 44, 135, 161 Gastrointestinal, 125, 133, 135, 141, 155, 160 Gastrointestinal tract, 135, 141, 155, 160 Gene Expression, 20, 22, 23, 135 Gene Therapy, 14, 34, 135 Genetic testing, 12, 35, 135 Genetics, 26, 31, 41, 43, 45, 46, 52, 135, 141 Genotype, 29, 51, 135, 149 Germ Cells, 135, 146 Germline mutation, 46, 135, 137 Gingival Hyperplasia, 4, 135 Gland, 135, 148, 151, 155, 157, 159 Glucose, 125, 130, 136, 137, 140 Glucuronic Acid, 136, 137 Glycoprotein, 136, 158, 160 Glycosaminoglycans, 7, 136 Governing Board, 136, 150 Graft, 71, 136, 138 Graft Rejection, 71, 136 Grafting, 129, 136 Granule, 25, 136 Granulocytes, 136, 156, 162

Growth, 11, 12, 20, 21, 23, 56, 121, 122, 123, 127, 134, 136, 140, 143, 145, 149, 159, 160 Growth factors, 11, 136 Guanylate Cyclase, 136, 146 H Half-Life, 136, 139 Haplotypes, 12, 136 Haptens, 120, 136 Heart Catheterization, 117, 136 Heart failure, 5, 6, 8, 9, 17, 19, 136 Heart-Lung Transplantation, 84, 137 Hematopoiesis, 137, 143 Heme, 25, 82, 130, 137, 148 Hemodynamics, 33, 57, 63, 65, 137 Hemoglobin, 22, 42, 121, 133, 137 Hemoglobinopathies, 135, 137 Hemolytic, 55, 137 Hemorrhage, 40, 137, 157, 162 Hemostasis, 137, 155 Heparin, 7, 49, 92, 137 Hereditary, 13, 61, 135, 137 Hereditary mutation, 135, 137 Heredity, 135, 137 Heterodimer, 26, 137 Heterogeneity, 26, 43, 51, 120, 137 Homeostasis, 6, 82, 137 Homologous, 120, 129, 135, 137, 143, 155, 158 Hormone, 47, 125, 130, 132, 133, 138, 140, 154, 156, 158, 159 Host, 124, 138, 141, 154 Humoral, 136, 138 Hybridomas, 138, 140 Hydralazine, 59, 92, 138 Hydrogen, 82, 124, 130, 138, 142, 144, 145, 147, 152 Hydrogen Peroxide, 82, 138, 142 Hydroxylysine, 128, 138 Hydroxyproline, 121, 128, 138 Hyperhomocysteinemia, 30, 130, 138 Hyperoxia, 82, 138 Hyperplasia, 4, 13, 48, 58, 66, 138 Hypersensitivity, 138, 141, 154 Hypertrophy, 8, 9, 124, 138, 144 Hypotensive, 84, 138 Hypothyroidism, 46, 48, 138 Hypoxemia, 58, 139 Hypoxia, 8, 20, 21, 22, 139 Hypoxic, 20, 83, 139 I Id, 76, 106, 112, 114, 139 Idiopathic, 4, 16, 65, 82, 139

Index 167

Iloprost, 27, 29, 38, 46, 53, 64, 74, 88, 139 Immune response, 122, 123, 136, 139, 143, 161 Immune system, 4, 124, 139, 141, 142, 144, 148, 160, 162 Immunodeficiency, 13, 47, 65, 139 Immunologic, 139, 143, 153 Immunology, 32, 43, 120, 139, 141 Immunosuppressive, 38, 139 Immunosuppressive therapy, 38, 139 Impairment, 20, 49, 139, 143 Implant radiation, 139, 140, 141, 152, 162 In situ, 7, 21, 139 In Situ Hybridization, 7, 139 In vitro, 10, 11, 13, 14, 17, 18, 19, 20, 22, 26, 67, 82, 135, 139 In vivo, 10, 17, 18, 22, 24, 26, 82, 135, 137, 139, 147, 159 Incision, 125, 139, 140 Indicative, 42, 139, 148, 160 Induction, 32, 82, 139 Infant, Newborn, 120, 139 Infarction, 139 Infection, 13, 124, 132, 139, 140, 142, 154, 157, 162 Inflammation, 13, 25, 82, 122, 125, 132, 134, 140, 141, 145, 148, 150, 154 Infusion, 5, 20, 29, 33, 38, 51, 52, 61, 74, 75, 78, 140 Ingestion, 140, 144 Inhalation, 29, 38, 53, 74, 120, 140 Initiation, 23, 140, 160 Insight, 14, 140 Insulin, 5, 140, 160 Insulin-dependent diabetes mellitus, 140 Interleukin-6, 10, 21, 140 Internal radiation, 140, 141, 152, 162 Interstitial, 35, 82, 125, 140, 141, 162 Intestinal, 26, 70, 88, 126, 140 Intestines, 119, 135, 140 Intoxication, 140, 162 Intracellular, 7, 14, 16, 23, 140, 146, 150, 151, 153, 156 Intravascular, 22, 50, 136, 140 Intravenous, 20, 34, 51, 52, 53, 74, 75, 140 Intrinsic, 14, 120, 140 Intubation, 127, 140 Invasive, 9, 18, 24, 140, 143 Investigative Techniques, 18, 141 Ions, 124, 131, 132, 138, 141 Irradiation, 82, 141, 162 Ischemia, 67, 141

K Kb, 98, 141 Kidney Disease, 79, 82, 98, 141 Kinetic, 17, 141 L Large Intestine, 131, 140, 141, 153 Larynx, 82, 141, 159 Lethal, 10, 141 Lethargy, 138, 141 Leukemia, 135, 141 Leukocytes, 125, 136, 141, 144, 146, 160 Leukotrienes, 123, 132, 141 Library Services, 112, 141 Life Expectancy, 9, 141 Ligaments, 129, 142 Ligands, 11, 142 Ligation, 40, 142 Linkage, 9, 10, 51, 142 Lipid, 5, 52, 123, 140, 142, 144, 147 Lipid Peroxidation, 142, 147 Lipopolysaccharide, 82, 142 Liposome, 14, 142 Liver, 4, 56, 58, 59, 82, 119, 123, 124, 128, 131, 135, 136, 137, 142, 150, 155 Liver scan, 142, 155 Liver Transplantation, 56, 59, 142 Lobe, 52, 142 Localized, 18, 22, 88, 119, 140, 142, 149, 155 Lung Transplantation, 24, 29, 40, 45, 52, 62, 64, 65, 71, 84, 117, 142 Lymph, 127, 133, 142 Lymphatic, 133, 140, 142, 156, 157 Lymphatic system, 142, 156, 157 Lymphocyte, 25, 122, 142, 143 Lymphoid, 122, 142 Lymphokines, 142, 143 Lytic, 25, 142 M Macrophage, 32, 49, 84, 142, 143 Macrophage Activation, 49, 142 Macrophage Inflammatory Protein-1, 32, 143 Magnetic Resonance Imaging, 6, 63, 143, 146, 155 Major Histocompatibility Complex, 136, 143 Malformation, 36, 143 Malignant, 54, 122, 143, 145, 152, 155 Mammary, 129, 143 Manifest, 5, 143 Medial, 11, 15, 123, 143

168

Primary Pulmonary Hypertension

Mediator, 52, 143, 155 MEDLINE, 99, 143 Melanin, 143, 149, 160 Membrane, 9, 20, 21, 23, 25, 40, 127, 130, 131, 134, 141, 143, 147, 154, 156, 160 Mental, iv, 5, 79, 98, 100, 127, 131, 134, 138, 143, 152, 155 Mental Disorders, 79, 143, 152 MI, 69, 118, 143 Microbiology, 67, 119, 143 Microorganism, 143, 162 Migration, 8, 143, 144 Mitochondria, 144, 147 Mitosis, 123, 144 Mitral Valve, 37, 144 Modeling, 18, 144 Modification, 121, 144, 152 Modulator, 10, 20, 144 Molecular, 6, 8, 12, 18, 19, 21, 22, 23, 31, 43, 50, 99, 101, 124, 129, 137, 144, 153, 159, 160 Molecule, 14, 82, 83, 122, 124, 131, 132, 133, 137, 144, 147, 149, 152, 153, 156, 159, 161 Monitor, 144, 146 Monoclonal, 138, 141, 144, 152, 162 Monocrotaline, 6, 22, 144 Monocytes, 32, 60, 140, 141, 143, 144 Mononuclear, 144, 160 Morphogenesis, 7, 144 Morphology, 142, 144 Motility, 144, 155 Multiple sclerosis, 119, 144 Myelofibrosis, 40, 144 Myocardial infarction, 25, 129, 143, 144, 161 Myocarditis, 13, 145 Myocardium, 143, 144, 145, 161 N NCI, 1, 78, 97, 128, 145 Need, 3, 20, 93, 94, 107, 120, 145, 159 Neonatal, 7, 44, 145 Neoplasm, 145, 155 Nephropathy, 141, 145 Nerve, 119, 121, 128, 135, 143, 144, 145, 147, 150, 154, 157, 160 Nervous System, 127, 143, 145, 158 Neural, 126, 138, 145 Neuromuscular, 119, 145 Neuromuscular Junction, 119, 145 Neuronal, 7, 145 Neurons, 135, 145, 158

Neuropeptide, 126, 145 Neurophysiology, 130, 145 Neurotoxic, 4, 145 Neurotoxicity, 5, 31, 145 Neurotransmitter, 119, 121, 125, 126, 145, 156 Neutrons, 141, 145, 152 Neutrophils, 136, 141, 143, 146 Nicardipine, 64, 146 Nifedipine, 4, 34, 35, 38, 45, 49, 52, 57, 58, 146 Nitric Oxide, 9, 15, 16, 17, 19, 23, 27, 30, 35, 46, 49, 50, 53, 56, 59, 65, 68, 69, 146 Nitrogen, 22, 120, 146, 160 Nitrogen Oxides, 22, 146 Nuclear, 20, 36, 53, 63, 134, 135, 146 Nuclear magnetic resonance imaging, 36, 146 Nuclei, 135, 143, 144, 145, 146, 147, 152 Nucleic acid, 139, 146 Nucleus, 122, 128, 130, 134, 144, 145, 146, 151, 152 O Ocular, 41, 146 Oocytes, 23, 146 Opacity, 130, 146 Ophthalmic, 146, 154 Opsin, 146, 154 Optic Disk, 129, 131, 147 Optic Nerve, 147, 154 Oral Health, 4, 147 Organelles, 22, 130, 144, 147, 149 Osteoclasts, 126, 147 Osteopetrosis, 54, 147 Outpatient, 147 Oxidants, 18, 147 Oxidation, 122, 130, 142, 147 Oxidation-Reduction, 147 Oxidative Stress, 82, 147 Oxides, 23, 146, 147 Oxygen Consumption, 134, 147, 153 Oxygenase, 25, 82, 148 Oxygenation, 40, 139, 148 P Palliative, 148, 158 Pancreas, 119, 124, 131, 140, 148, 160 Patch, 19, 129, 148 Pathogenesis, 8, 11, 12, 13, 22, 31, 33, 40, 42, 57, 62, 88, 148 Pathologic, 123, 124, 129, 138, 148 Pathologic Processes, 123, 148

Index 169

Pathophysiology, 13, 16, 17, 18, 22, 25, 26, 31, 40, 148 Peptide, 26, 70, 74, 75, 88, 121, 125, 126, 148, 151, 159 Perceived risk, 12, 148 Perfusion, 19, 21, 28, 63, 139, 148 Pericardial Effusion, 43, 148 Pericarditis, 13, 148 Pericardium, 148, 161 Peripheral Vascular Disease, 82, 148 Peritoneum, 148 Peritonitis, 67, 148 Perivascular, 126, 148 Phagocyte, 147, 148 Pharmacologic, 8, 65, 121, 136, 149, 159 Pharmacotherapy, 4, 39, 55, 149 Phenotype, 8, 10, 14, 20, 149 Phentermine, 23, 30, 149 Phenylalanine, 149, 160 Phospholipases, 149, 156 Phosphorus, 126, 149 Physiologic, 7, 17, 21, 120, 134, 136, 149, 151, 153 Pigments, 126, 149, 154 Plants, 120, 126, 136, 144, 149, 159 Plaque, 4, 149 Plasma, 21, 23, 30, 34, 46, 75, 122, 126, 127, 133, 137, 149 Plasma cells, 122, 149 Plasmid, 14, 149, 161 Plastids, 147, 149 Platelet Activation, 149, 156 Platelet Aggregation, 25, 34, 133, 139, 146, 149, 151, 159 Platelets, 146, 149, 150, 159 Pneumonia, 82, 129, 150 Pneumonitis, 13, 35, 150 Polymorphic, 10, 150 Polymorphism, 12, 52, 150 Portal Hypertension, 16, 150 Portal Vein, 150 Posterior, 121, 123, 148, 150 Postnatal, 21, 150 Postsynaptic, 150, 156 Potassium, 19, 119, 150 Potentiation, 150, 156 Practice Guidelines, 100, 150 Precursor, 123, 132, 133, 149, 150, 160 Prevalence, 46, 150 Prognostic factor, 67, 74, 150 Progression, 18, 121, 150

Progressive, 8, 9, 11, 12, 18, 127, 128, 131, 136, 149, 150 Proline, 128, 138, 150 Promoter, 12, 14, 23, 26, 150 Prophase, 146, 151, 158 Prophylaxis, 4, 151 Prostaglandin, 25, 49, 78, 133, 151, 159 Prostaglandin Endoperoxides, 133, 151, 159 Prostaglandins A, 151 Prostate, 124, 151, 160 Protease, 128, 151 Protein Binding, 7, 151 Protein C, 22, 121, 124, 151 Protein S, 124, 151, 158 Protocol, 16, 151 Protons, 138, 152 Proximal, 63, 131, 152, 155 Psychiatry, 152, 161 Psychic, 143, 152 Psychoactive, 152, 162 Public Policy, 99, 152 Pulmonary Artery, 6, 8, 9, 12, 15, 18, 19, 28, 32, 35, 37, 48, 54, 66, 83, 125, 144, 152, 161 Pulmonary Circulation, 16, 21, 64, 152 Pulmonary Edema, 47, 152 Pulmonary Embolism, 82, 152 Pulse, 18, 117, 144, 152 Q Quality of Life, 6, 19, 66, 152 R Race, 144, 152 Radiation, 134, 140, 141, 152, 155, 162 Radiation therapy, 134, 140, 141, 152, 162 Radioactive, 24, 125, 136, 138, 139, 140, 141, 142, 146, 152, 155, 162 Radiolabeled, 141, 152, 162 Radiotherapy, 125, 141, 152, 162 Randomized, 24, 77, 132, 153 Reagent, 25, 153 Receptor, 6, 7, 8, 10, 11, 12, 13, 20, 21, 24, 26, 39, 41, 43, 46, 57, 61, 67, 84, 119, 122, 153, 155, 156 Receptors, Serotonin, 153, 155 Recombinant, 11, 153, 161 Recombination, 12, 135, 153 Rectum, 122, 125, 131, 135, 141, 151, 153 Red blood cells, 16, 49, 133, 137, 148, 153 Reductase, 25, 153 Refer, 1, 145, 153, 159 Refraction, 153, 157

170

Primary Pulmonary Hypertension

Regimen, 4, 128, 132, 149, 153 Regurgitation, 43, 153 Reproductive cells, 135, 137, 153 Research Design, 18, 153 Research Support, 16, 153 Respiration, 33, 126, 144, 153, 154 Respiratory distress syndrome, 82, 153 Respiratory Physiology, 31, 39, 40, 42, 46, 49, 55, 58, 60, 62, 70, 71, 153, 161 Restoration, 153, 162 Resuscitation, 50, 153 Retina, 32, 41, 129, 131, 147, 154 Retinal, 32, 131, 147, 154 Retinal Vein, 32, 154 Retinal Vein Occlusion, 32, 154 Retinol, 154 Retroviral vector, 135, 154 Retrovirus, 13, 154 Rheumatism, 154 Rheumatoid, 25, 147, 154 Rheumatoid arthritis, 25, 154 Rhodopsin, 146, 154 Ribose, 119, 154 Risk factor, 13, 47, 138, 154 Rod, 124, 128, 154 Root Planing, 4, 154 S Salivary, 131, 154 Salivary glands, 131, 154 Saphenous, 129, 154 Saphenous Vein, 129, 154 Sarcoma, 13, 155 Scans, 12, 155 Schizoid, 155, 162 Schizophrenia, 155, 162 Schizotypal Personality Disorder, 155, 162 Scleroderma, 13, 16, 155 Screening, 49, 128, 155 Secretion, 138, 140, 155, 160 Segregation, 153, 155 Sensibility, 121, 155 Sepsis, 82, 155 Septal, 38, 155 Septic, 82, 155 Serotonin, 5, 12, 15, 31, 46, 48, 52, 66, 88, 130, 134, 135, 145, 149, 153, 155, 160 Serous, 133, 155 Serum, 22, 51, 148, 155, 160 Shock, 64, 82, 155 Shunt, 6, 44, 156 Side effect, 24, 91, 94, 120, 124, 156, 159 Signal Transduction, 12, 16, 20, 25, 156

Skeletal, 128, 156 Skeleton, 151, 156 Skull, 156, 158 Smooth muscle, 6, 8, 9, 10, 12, 15, 16, 19, 20, 23, 37, 48, 52, 66, 70, 151, 156 Social Environment, 152, 156 Sodium, 24, 30, 50, 133, 156 Solid tumor, 121, 156 Somatic, 132, 138, 144, 156 Specialist, 106, 131, 156 Species, 18, 121, 133, 144, 152, 156, 157, 160, 162 Specificity, 43, 120, 156 Spectrum, 13, 157 Sperm, 128, 135, 137, 153, 157 Sphincter, 141, 157 Spleen, 82, 142, 157 Splenomegaly, 147, 157 Sporadic, 8, 9, 10, 12, 13, 157 Stabilization, 22, 157 Staging, 155, 157 Steel, 128, 157 Stellate, 69, 157 Stellate Ganglion, 69, 157 Stimulant, 130, 149, 157 Stimulus, 9, 16, 157, 158 Stomach, 119, 131, 133, 135, 138, 140, 157 Stress, 11, 60, 82, 127, 147, 154, 157 Stroke, 79, 98, 126, 157 Subacute, 140, 157 Subclinical, 140, 157 Subspecies, 156, 157 Substrate, 25, 82, 157 Sulfates, 7, 157 Sulfuric acid, 157 Sympathomimetic, 130, 133, 149, 158 Symptomatic, 5, 66, 77, 158 Synaptic, 145, 156, 158 Systemic, 13, 24, 36, 92, 122, 125, 133, 137, 140, 141, 152, 155, 158, 161, 162 Systolic, 6, 33, 69, 70, 138, 158 T Telangiectasia, 13, 158 Temporal, 7, 9, 10, 158 Teratogenic, 131, 158 Testosterone, 153, 158 Tetracycline, 10, 158 Theophylline, 4, 158 Therapeutics, 10, 15, 77, 93, 141, 158 Thoracic, 33, 45, 52, 54, 157, 158 Threshold, 138, 158 Thrombin, 134, 149, 151, 158

Index 171

Thrombocytopenia, 55, 158 Thromboembolism, 32, 58, 83, 158 Thrombomodulin, 151, 158 Thrombosis, 42, 46, 60, 151, 157, 158 Thromboxanes, 123, 132, 151, 159 Thrombus, 9, 129, 139, 149, 159 Thyroid, 68, 125, 138, 159, 160 Thyrotropin, 138, 159 Tolerance, 4, 82, 119, 159 Tomography, 28, 129, 155, 159 Tone, 5, 20, 159 Tonus, 159 Tooth Preparation, 119, 159 Topical, 29, 138, 159 Toxic, iv, 144, 159 Toxicity, 131, 159 Toxicology, 19, 100, 159 Toxin, 133, 159 Trachea, 125, 141, 159 Traction, 128, 159 Transcriptase, 154, 159 Transcription Factors, 14, 15, 22, 26, 160 Transduction, 16, 156, 160 Transfection, 14, 124, 135, 160 Translational, 21, 160 Transmitter, 119, 143, 160 Transplantation, 6, 40, 54, 55, 62, 75, 143, 160 Tryptophan, 128, 155, 160 Tumor marker, 124, 160 Tumor Necrosis Factor, 7, 160 Type 2 diabetes, 5, 160 Tyrosine, 11, 160 U Ubiquitin, 22, 160 Unconscious, 139, 160 Urethra, 124, 151, 160 Urine, 124, 131, 160 V Vaccine, 152, 160 Vacuoles, 147, 160 Vagina, 130, 160 Valves, 160, 161

Vascular endothelial growth factor, 7, 21, 160 Vascular Resistance, 5, 8, 15, 16, 18, 53, 64, 88, 161 Vasoactive, 17, 26, 70, 88, 161 Vasoconstriction, 9, 10, 19, 20, 23, 25, 133, 161 Vasodilation, 20, 49, 139, 161 Vasodilator, 9, 17, 29, 33, 45, 69, 70, 71, 74, 75, 125, 126, 138, 146, 161 Vector, 14, 160, 161 Vein, 121, 140, 146, 150, 154, 161 Ventilation, 64, 71, 161 Ventricle, 6, 122, 144, 152, 158, 161 Ventricular, 6, 8, 36, 37, 38, 48, 65, 66, 67, 69, 144, 161 Ventricular Function, 6, 37, 161 Ventricular Pressure, 37, 48, 161 Ventricular Remodeling, 6, 161 Venules, 125, 126, 133, 161 Verapamil, 35, 161 Veterinary Medicine, 99, 161 Viral, 6, 12, 25, 132, 154, 160, 161 Viral vector, 12, 161 Virus, 13, 47, 65, 124, 149, 154, 160, 161 Vitreous, 131, 154, 162 Vitreous Hemorrhage, 131, 162 Vitro, 11, 13, 22, 137, 162 Vivo, 23, 162 Voltage-gated, 9, 23, 37, 162 W White blood cell, 122, 141, 142, 149, 162 Withdrawal, 4, 162 Wound Healing, 82, 162 X Xenograft, 121, 162 X-ray, 117, 123, 129, 141, 146, 152, 155, 162 X-ray therapy, 141, 162 Y Yeasts, 149, 162 Z Zymogen, 151, 162

172

Primary Pulmonary Hypertension