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

OSTEOGENESIS IMPERFECTA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENC...

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 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., 1960Osteogenesis Imperfecta: 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: 0-597-84538-7 1. Osteogenesis Imperfecta-Popular works. I. Title.

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

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

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

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

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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON OSTEOGENESIS IMPERFECTA..................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Osteogenesis Imperfecta ................................................................ 5 E-Journals: PubMed Central ....................................................................................................... 24 The National Library of Medicine: PubMed ................................................................................ 26 CHAPTER 2. NUTRITION AND OSTEOGENESIS IMPERFECTA ........................................................... 71 Overview...................................................................................................................................... 71 Finding Nutrition Studies on Osteogenesis Imperfecta............................................................... 71 Federal Resources on Nutrition ................................................................................................... 73 Additional Web Resources ........................................................................................................... 74 CHAPTER 3. ALTERNATIVE MEDICINE AND OSTEOGENESIS IMPERFECTA .................................... 75 Overview...................................................................................................................................... 75 National Center for Complementary and Alternative Medicine.................................................. 75 Additional Web Resources ........................................................................................................... 78 General References ....................................................................................................................... 79 CHAPTER 4. DISSERTATIONS ON OSTEOGENESIS IMPERFECTA ...................................................... 81 Overview...................................................................................................................................... 81 Dissertations on Osteogenesis Imperfecta.................................................................................... 81 Keeping Current .......................................................................................................................... 82 CHAPTER 5. CLINICAL TRIALS AND OSTEOGENESIS IMPERFECTA ................................................. 83 Overview...................................................................................................................................... 83 Recent Trials on Osteogenesis Imperfecta.................................................................................... 83 Keeping Current on Clinical Trials ............................................................................................. 86 CHAPTER 6. PATENTS ON OSTEOGENESIS IMPERFECTA ................................................................. 89 Overview...................................................................................................................................... 89 Patents on Osteogenesis Imperfecta............................................................................................. 89 Patent Applications on Osteogenesis Imperfecta ......................................................................... 93 Keeping Current .......................................................................................................................... 95 CHAPTER 7. BOOKS ON OSTEOGENESIS IMPERFECTA ..................................................................... 97 Overview...................................................................................................................................... 97 Book Summaries: Federal Agencies.............................................................................................. 97 Book Summaries: Online Booksellers........................................................................................... 98 Chapters on Osteogenesis Imperfecta........................................................................................... 99 CHAPTER 8. MULTIMEDIA ON OSTEOGENESIS IMPERFECTA ........................................................ 105 Overview.................................................................................................................................... 105 Video Recordings ....................................................................................................................... 105 CHAPTER 9. PERIODICALS AND NEWS ON OSTEOGENESIS IMPERFECTA ..................................... 107 Overview.................................................................................................................................... 107 News Services and Press Releases.............................................................................................. 107 Newsletter Articles .................................................................................................................... 109 Academic Periodicals covering Osteogenesis Imperfecta ........................................................... 109 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 111 Overview.................................................................................................................................... 111 U.S. Pharmacopeia..................................................................................................................... 111 Commercial Databases ............................................................................................................... 112 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 115 Overview.................................................................................................................................... 115 NIH Guidelines.......................................................................................................................... 115 NIH Databases........................................................................................................................... 117

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Other Commercial Databases..................................................................................................... 119 The Genome Project and Osteogenesis Imperfecta..................................................................... 119 APPENDIX B. PATIENT RESOURCES ............................................................................................... 125 Overview.................................................................................................................................... 125 Patient Guideline Sources.......................................................................................................... 125 Associations and Osteogenesis Imperfecta................................................................................. 133 Finding Associations.................................................................................................................. 134 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 137 Overview.................................................................................................................................... 137 Preparation................................................................................................................................. 137 Finding a Local Medical Library................................................................................................ 137 Medical Libraries in the U.S. and Canada ................................................................................. 137 ONLINE GLOSSARIES................................................................................................................ 143 Online Dictionary Directories ................................................................................................... 145 OSTEOGENESIS IMPERFECTA DICTIONARY.................................................................... 147 INDEX .............................................................................................................................................. 199

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with osteogenesis imperfecta 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 osteogenesis imperfecta, 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 osteogenesis imperfecta, 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 osteogenesis imperfecta. 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 osteogenesis imperfecta, 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 osteogenesis imperfecta. The Editors

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

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

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

How Common Is Hearing Impairment in Osteogenesis Imperfecta? Source: Journal of Laryngology and Otology. 115(4): 280-282. April 2001. Contact: Available from Royal Society of Medicine Press Limited. Publications Subscription Department, P.O. Box 9002, London W1A 0ZA, United Kingdom. E-mail: [email protected]. Summary: Hearing impairment has long been recognized as a common feature in osteogenesis imperfecta, a genetic disorder involving defective development of the connective tissue and characterized by brittle and fragile bones. The figures in some publications could be taken to imply that, with increasing age, the proportion of osteogenesis imperfecta patients with hearing impairment approaches 100 percent. This

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Osteogenesis Imperfecta

article reports on a study that examined the incidence of hearing loss in a large survey of 1,394 patients with osteogenesis imperfecta. The authors found that the most common age of onset was in the second, third, and fourth decades of life. At the age of 50, approximately 50 percent of the patients had symptoms of hearing impairment; over the next 20 years there was little further increase. Differences were shown between patients with different clinical types of osteogenesis imperfecta as delineated in the Sillence classification; hearing loss was significantly less common in the type IV disease than in the type I disorder. Among the 29 families with osteogenesis imperfecta type IA there were distinct differences in the likelihood of hearing loss. These findings provide insights which will be valuable in giving patients advice on the likelihood of developing hearing loss in the future. 1 figure. 3 tables. 15 references. •

Treatment of Mandibular Cysts Associated with Osteogenesis Imperfecta Source: Journal of Dentistry for Children. 67(1): 64-66. January-February 2000. Contact: Available from American Society of Dentistry for Children. John Hancock Center, 875 North Michigan Avenue, Suite 4040, Chicago, IL 60611-1901. (312) 943-1244. Summary: Osteogenesis imperfecta (OI) belongs to a group of rare hereditary disorders that are characterized by abnormal bone fragility and a variety of associated disorders. Fractures occur mainly in the extremities. Fractures in the head and face are rarely found, however. The appearance of cysts in the mandible (lower jaw) in association with OI is critical, not only because cysts increase the risk of fractures, but because the prolonged regeneration of bones makes treatment more difficult. This article reviews the treatment of mandibular cysts associated with OI. The authors discuss the symptoms and causes of OI, historical classifications and early case reports, and then present the case of a fifteen year old boy with OI presenting with a large radicular cyst in the mandible. The boy reported approximately twenty spontaneous fractures of his extremities in his lifetime, which were treated conservatively. The authors describe his symptoms and treatment used for the cyst. In this case, because of the size and extension of the cyst, and in spite of the questionable healing quality of the bone, it was decided to do a cystostomy and remove tooth 73. The integrity of the mandible was restored and treatment was completed 6 months postoperatively. 5 figure. 9 references.

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Recent Findings in Classification of Osteogenesis Imperfecta by Means of Existing Dental Symptoms Source: Journal of Dentistry for Children. 65(5): 306-309. September-October 1998. Contact: Available from American Society of Dentistry for Children. John Hancock Center, 875 North Michigan Avenue, Suite 4040, Chicago, IL 60611-1901. (312) 943-1244. Summary: This article reviews recent findings in the classification of osteogenesis imperfecta (OI) by means of existing dental symptoms. The authors review the classification of osteogenesis, and describe a clinical study conducted on 49 patients and a survey in which 117 OI-affected persons or their parents had participated. Through this data, the authors established the frequency of dental caries, tooth discolorations and abrasions, as well as radiological abnormalities of teeth in cases of OI. Considering the skeletal severity and the dental symptoms, it was shown that, with an average fracture rate of 2.1, the occurrence of dentinogenesis imperfecta was most frequent in 72.7 percent of the cases. However, it was not possible to confirm the assumption that the probability of a dentinogenesis imperfecta occurrence increases with a rise in fracture rate and an increase in affected bones. The most important criteria for designating dentinogenesis imperfecta as a condition was the existence of pathological tooth

Studies

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discolorations, after all other causes of discoloration were excluded by differential diagnosis. The authors conclude with a call for the standardization of classification systems internationally for OI and dentinogenesis imperfect (DI). 1 figure. 9 tables. 20 references.

Federally Funded Research on Osteogenesis Imperfecta The U.S. Government supports a variety of research studies relating to osteogenesis imperfecta. 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 osteogenesis imperfecta. 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 osteogenesis imperfecta. The following is typical of the type of information found when searching the CRISP database for osteogenesis imperfecta: •

Project Title: IMPERFECTA

ALENDRONATE

USE

IN

MODELS

OF

OSTEOGENESIS

Principal Investigator & Institution: Raggio, Cathleen L.; Associate Professor; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (Taken from the application): Recent clinical reports of apparent successful bisphosphonate therapy in children with osteogenesis imperfecta (OI) appear very promising. Previously, we demonstrated that the bisphosphonate, alendronate significantly, reduces fracture incidence and increase density in the growing oirn/oim mouse, an animal model of moderate-severe OI. However, data from that study also indicated that the quality of the newly formed bone was not optimal, and that reductions in long bone growth, might occur with treatment. However, since OI. is a heterogeneous disease clinically and most patients have unique mutations in collagen I formation, there may be a difference in response to treatment with bisphosphonates both short and long term. The long range goal of our studies is to evaluate bisphosphonate treatment in mouse models which have collagen abnormalities analogous to humans, i.e. ,decreased collagen content, abnormal collagen fibers, abnormal collagen packing. The proposed study will test the hypothesis that in 3 different mouse models of O.I. The first is the oim/oim mouse; the second a transgenic mouse which resembles mild-moderate O.I. The third is the new knock-in mouse (Brtl) which resembles mild O.I. The mice will be treated from age 2-14 weeks with alendronate. Bone quality will be assessed before and after treatment by radiographic 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).

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analysis of the number of fractures, of bone and tooth density and geometry. Analysis of bone ultra structure and histology, and mechanical testing of whole bones; methodologies that have all been used successfully in our previous studies with oimj/oim mice. Investigation of specific aspects of alendronate treatment will provide information critical to the determination of how to proceed with individualized treatment of infants and children with different types of O.I. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-RESORPTIVES FOR DYSREGULATED BONE REMODELING IN OL Principal Investigator & Institution: Camacho, Nancy P.; Associate Scientist; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): It is well established that patients with the collagenbased disease osteogenesis imperfecta (OI) have increased bone turnover (increased degradation and reduced formation). Accordingly, the reports of successful therapy in children with OI with the anti-resorptive agents bisphosphonates are quite exciting, but not unexpected. Despite this apparent success, there are still concerns surrounding the use of anti-resorptive agents in children and in women of childbearing age. Namely, the persistence of the drug in bone tissue over time could have unforeseen consequences, such as adverse effects on fetal development. In addition, it is not known if fracture healing, a biological process that requires extensive resorptive activity, would be compromised in patients treated with bisphosphonates. Further insight into the precise molecular and cellular mechanisms by which bone turnover is increased in OI could lead to more specific targeting of drugs, such that benefits similar to those achieved with bisphosphonate therapy could be realized without potential adverse effects. An exciting potential new therapy would be the use of osteoprotegerin (OPG), a naturally occurring soluble factor synthesized by osteoblasts, which blocks binding of Receptor Activator of NF-kB Ligand (RANKL) to osteoclast precursors and thereby inhibits osteoclastogenesis. The goals of this proposal are to: 1) use the growing oim1dim mouse, an established animal model of moderate-to-severe OI, to determine if treatment with OPG will result in improved bone properties and reduced fracture rate without compromised fracture healing. 2) determine if osteoclasts in the oimloim mice exhibit increased resorptive activity as a result of inappropriate signaling from RANKL produced by osteoblasts, or inappropriate signaling from the presence of abnormal bone mineral, and 3) determine if osteoclasts from patients with OI exhibit similar defective resorptive activity. The specific aims of this proposal are: 1) To treat growing oim1dim mice with OPG for 3 or 6 months, and evaluate specific bone properties, including fracture number, density, geometry, mechanical strength, mineral quality and histomorphometric parameters. Fracture healing will also be evaluated by creation of a closed transverse femoral fracture in the oim1bim mice after OPG treatment. 2) To culture osteoclast precursor cells derived from oim1bim bone marrow cells on bovine bone slices either with RANKIL or with oimldim osteoblasts, and evaluate resorptive activity; To culture osteoclast precursor cells derived from oim1bim bone marrow cells with RANKIL on bone substrates prepared from either oim/bim or +/+ calvarial bone and quantitate resorptive activity. 3) To culture osteoclast precursors from human OI peripheral blood monocytes and similarly evaluate their resoprtive active. The information gained from these studies will permit design of improved therapeutic protocols so that new modalities of treatment for children and adults with OI could be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

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Project Title: BIOMECHANICAL SIGNALS AND CARDIAC REMODELING Principal Investigator & Institution: Mcculloch, Andrew D.; Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 25-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The overall goal of this proposal is to examine the role that the cardiac extracellular matrix (ECM) plays in the growth and remodeling of ventricular myocardium, both by its contribution to the mechanics of the ventricular wall and by mediating mechanotransduction via cell-matrix interactions. In preliminary studies, ECM mutations in vivo led to significant perturbations of ventricular development in the osteogenesis imperfecta murine (oim) and significantly impaired post-infarction remodeling in the decorin-null (DKO) mouse. In vitro studies implicate integrins as stretch transducers in isolated cardiac cells. There are three specific aims: (1) to investigate how deficiency of type I collagen in the ECM alters myocardial mechanics and leads to developmental adaptations in myocardial structure, time courses of left ventricular (LV) residual strain, myofiber geometry, and orientation will be measured in relation to the postnatal development of collagen matrix and myocardial stiffness in oim and wildtype littermates. A novel in vitro assay using neonatal cardiac myocytes cultured on elastic membranes patterned with collagen microchannels will be used to test the hypothesis that mechanical strain can regulate postnatal myofiber alignment. (2) DKO mice will be used to test the hypothesis that deletion of this small proteoglycan dysregulates post-infarction scar structure, mechanics and ventricular remodeling. Transmission electron microscopy shows abnormalities of microfibril organization in scar collagen of DKO mice. Therefore, mechanical properties will be measured in scars of DKO mice and wildtype littermates 2-8 weeks post-infarction. Microstructural models will be used to investigate the structural basis of altered scar mechanical properties. DKO and WT mice will be followed 4-6 months post-infarction to confirm the hypothesis that dysregulated scar structure accelerates the transition to congestive heart failure, as strongly suggested by preliminary observations. (3) Preliminary studies used novel techniques to micropattern aligned neonatal ventricular myocyte (NVM) cultures and subject them to anisotropic biaxial stretch. Micropatterned myocytes stretched transverse to the myofiber axis exhibited a significant hypertrophic response compared with those in which principal stretch was applied parallel to the myofibrils. By growing cells on different extracellular matrices, function-blocking antibodies and peptides will be used to determine whether these differential responses to anisotropic strain patterns are mediated via specific cell-matrix interactions while carefully controlling for cell shape, cell-cell contact and cell-matrix adhesion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOMOLECULAR MECHANICS OF COLLAGEN MONOMERS AND FIBRILS Principal Investigator & Institution: Phillips, Charlotte L.; Associate Professor; Biochemistry; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 08-MAR-2002; Project End 28-FEB-2003 Summary: (provided by applicant): Biomechanical stability and strength of connective tissues have long been attributed to covalent intermolecular crosslinks between collagen monomers. Type I collagen, a major component of bone, tendon, skin, and the vasculature, is normally heterotrimeric, consisting of two al (I) chains and a single a2(I) chain, [al(I)2a2(I)]. However, type I collagen in oim mice is exclusively composed of al(I) homotrimers, [al(I)3] (result of a null mutation in the a2(I) gene). Oim mice are a superb

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model system for examining the functional necessity of the a2(I) chain. We hypothesize that the absence of a2(I) chains perturbs collagen fibril formation, collagen-collagen interactions, and intra- and inter-molecular crosslinking, compromising the structural and biomechanical integrity of connective tissues. In vivo studies using oim mice demonstrate that the presence of type I collagen homotrimers significantly decreases the biomechanical integrity of bone, tendon, skin and aorta. Further analyses using oim mice suggest non-covalent collagen intra- and intermolecular interactions and organization maybe the critical factors regulating mechanical integrity rather than collagen crosslinking. These results question the dogma that covalent intermolecular crosslinks between collagen monomers are the principal determinants of stability and biomechanical integrity of the fibrillar architecture, and compel us to consider other forces and interactions, such as the inherent mechanical properties of individual collagen monomers and non-covalent protein-protein interactions. Recent advances in the application of atomic force microscopy now make it possible to analyze inherent mechanical properties of single biomolecules and molecule-molecule interactions. We propose to use atomic force microscopy to define the role of a2(I) chains 1) in the inherent mechanical integrity of collagen monomers, 2) in non-covalent collagencollagen interactions, and 3) in the inherent mechanical integrity of collagen fibrils, as well as provide a powerful new tool for defining and understanding the pathogenesis of fibrillar collagen mutations and other extracellular matrix components and their role in connective tissue disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE REPAIR BY ALLOGENIC MSC IN NON-ABLATED ANIMAL Principal Investigator & Institution: Lou, Jueren; Orthopaedic Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): There are more than one million orthopaedic operations performed each year in the United States, which require bone healing and repair. Developing a new, effective method to enhance bone healing and repair may directly impact clinical outcomes. Such a method can avoid invasive procedures for harvesting bone graft and can also address other problems of bone grafting, such as failure of complete resorption of the grafted bone, difficulty in shaping the bone graft to completely fill the defect, and lack of sufficient bone graft substance for large and extensive bone defects in the clinic. Previous studies showed that implantation of autologous bone marrow derived mesenchymal stem cells (MSC) generates bone formation in vivo. We further demonstrated that bone morphogenetic protein-2 (BMP-2) gene transfer in MSC enhances bone formation compared to autologous implantation of MSC alone. Recent evidence demonstrated that allogeneic bone marrow transplantation into children with severe osteogenesis imperfecta enhances bone formation, which resulted from engraftment of allogeneic MSC and that implantation of allogeneic marrow soaked porous hydroxyapatite ceramics leads to histological bone formation in rats. Thus, we hypothesize that in conjunction with the short term administration of the immunosuppressant, BMP-2 gene transferred allogeneic MSC can survive for a period of time following implantation into bone defect sites of non-ablated recipients. These MSC can overexpress BMP-2 protein for a period of time in situ, which induces both implanted allogeneic MSC and host mesenchymal progenitor cells to express bone matrixes and to form bone. Our aims are:1. To investigate the repair of femur defects in non-ablated rats with BMP-2 gene transferred allogeneic MSC for repair.2. To investigate the fate of implanted allogeneic MSC in femur defect site of non-ablated rats.

Studies

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The ultimate goal of this proposal is to develop percutaneous injection procedure to facilitate bone repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMISTRY AND BIOLOGY OF COLLAGEN Principal Investigator & Institution: Raines, Ronald T.; Professor; Biochemistry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2004; Project Start 15-JUL-1996; Project End 31-MAR-2008 Summary: (provided by applicant): Collagen comprises one-third of the protein in humans. Collagen abnormalities are associated with a wide variety of human diseases, such as osteogenesis imperfecta, Ehlers-Danlos syndrome, and some types of osteoporosis and arthritis. The long-term objective of the proposed research is to reveal in atomic detail the chemical basis for the unique triple-helical structure of collagen, and the roles of collagen in human health and disease. Specific Aims: (1) Basis for Triple Helix Stability. The hypothesis to be evaluated is that individual strands of collagen are preorganized to form a triple helix. The experiments make use of collagen strands containing nonnatural amino acids (in particular, 4-fluoroproline diastereomers and Nmethylglycine) that impose distinct stereoelectronic and steric effects. Data on conformational stability will be reinforced by computational and structural analyses. (2) Cystine Knot Templates. A collagen triple helix cross-linked by two disulfide bonds (that is, a cystine knot) can contain three different strands, and provides a realistic mimic of natural collagen. An efficient solid-phase synthesis of triple helices crosslinked by a cystine knot will be developed, and those helices will be used to evaluate the contribution of the ladder of interstrand main-chain-main-chain hydrogen bonds to collagen stability, assess the ability of a single strand of collagen to invade a triple helix, and self-assemble long, well-defined triple helices. (3) Encoded Collagen Library. Phage display of a cystine knot will be used to generate encoded libraries of collagen triple helices. These libraries will be screened for triple helices with high affinity for collagenbinding proteins, in particular, the adhesin protein from the pathogenic bacterium Staphyloccocus aureus. Significance: The results of the proposed research will provide new insights into the structure and conformational stability of the collagen triple helix and on its interaction with other proteins, and could ultimatley lead to the creation of collagen mimics and collagen-based biomaterials with important therapeutic applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLLAGEN GENE TARGETING WITH AAV VECTORS Principal Investigator & Institution: Russell, David W.; Assistant Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Collagen Gene Targeting with Adeno-Associated Virus Vectors Osteogenesis Imperfecta (OI) is a genetic disease caused by mutations in the type I collagen genes COLIAI or COL1 42 that can result in major skeletal abnormalities, deformities, frequent fractures, pain, and premature death. Severe forms of OI are typically caused by dominant mutations that disrupt the Collagen triple helix, so an effective treatment will require removal or correction of dominant, mutant alleles. The long-term objective of this proposal is to develop a novel approach for the treatment of OI based on the transplantation of genetically modified autologous mesenchymal stem cells (MSCs) that are expected to produce bone-forming osteoblasts in vivo.

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Adenoassociated virus (AAV) vectors have been shown to efficiently introduce specific genetic modifications into homologous chromosomal sequences, and here they will be used both to knockout and correct mutant, human COL 1A I alleles. Experiments will be performed with an existing collection of OI fibroblasts with defined COLIA1 mutations, and with an OI MSC bank established and characterized here. In one strategy, a single AAV targeting vector will be used to knockout any COL 1A allele, with the goal of converting severe OI due to helix-disrupting mutations to a mild form of OI due to a single null allele. In other strategies, AAV targeting vectors will be designed to correct specific COL 1A1 mutations and create wild-type alleles. Several approaches will be developed to select for cells that have undergone AAV-mediated gene targeting and express normal COL1 1A genes, with the goal of simplifying the ex vivo manipulations that would be used in future clinical trials. The proliferative and muItilineage potential of gene-targeted MSCs will be assessed by in vitro assays and also by an in vivo boneforniing assay after implantation in immunodeficient mice. Mixtures of MSCs marked with reporter genes will be assayed together to assess proliferation and bone formation when MSCs with different COLIA] genotypes coexist. In order to promote the engraftment of genetically modified MSCs, we will use chemical inducers of dimerization to multimerize engineered growth factor receptors and provide an inducible cell proliferation switch to MSCs. This switch will provide a method for pharmacologically controlled in vivo expansion of MSCs after transplantation. These studies are intended to lay the groundwork for future clinical trials for OI and other diseases that could benefit from the transnlantation of autologous genetically modified MSCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLAGEN-PROTEOGLYCAN INTERACTION IN CONNECTIVE TISSUE Principal Investigator & Institution: San Antonio, James D.; Assistant Professor of Medicine; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Over 300 mutations in type I collagen are associated with heritable connective tissue (CT) disorders in humans, characterized by altered matrix assembly, stability, and function. Proteoglscans', (PGs) including decorin, keratocan and lumican reside on type I collagen fibrils in various tissues, and are proposed to regulate fibril assembly and lateral association. We propose that such PGtype I collagen interactions are key regulators of matrix structure in healthy tissues, and that their disruption may be the underlying mechanism of certain CT diseases. We specifically mapped the spatial relationships between ligand-binding sites and mutation positions on type I collagen (DiLullo et al., 2002, J. Biol. Chem, 277, 4223), and reported that PGs may impact upon a number of type I collagen functions. Despite this, their sites of interaction remain poorly defined. Moreover, our map revealed that some mutations for osteogenesis imperfecta and other diseases co-localize with putative PG-binding sites, as do triple helical regions that lack reported mutations, further implicating PGcollagen interactions as key regulators of matrix structure. Thus, to better define the contribution of collagen-PG interactions to healthy tissues and to CT diseases, we will: 1) Synthesize type I collagen mimetic triple helical peptides (THPs) carrying candidate PG-binding sequences, and use them to construct a collagen peptide microarray; 2) Purify type I collagen-binding PGs and screen for their binding sites in type I collagen through use of the peptide microarray, and by affinity coelectrophoresis; and 3)

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Generate recombinant human Ope I collagens carrying mutated PG-binding regions and assess the effect on PG-collagen interactions and collagen fibrillogenesis. This work will: 1) increase our understanding of the role of PGs in type I collagen assembly, function, and in human diseases, 2) explore the feasibility of collagen peptide microarrays for the functional screening of collagen-intcractive ligands, and 3) lead the way to developing transgenic models for probing the in vivo function of PG-type I collagen interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--INFRARED IMAGING Principal Investigator & Institution: Paschalis, Eleftherious P.; Hospital for Special Surgery New York, Ny 10021 Timing: Fiscal Year 2002 Summary: The biomedical research base and the pilot and feasibility projects in the proposed Core Center all require mineral analysis at high spatial resolution. Fourier transform infrared spectroscopy is well suited for the study of both hard and soft tissues. It provides information on all tissue compartments, including mineral, mineral substituting carbonate, collagen, non-collagenous proteins, lipids, and proteoglycans. The Infrared (IR) Imaging Core will provide standard FTIR analyses along with infrared images acquired using a newly developed methodology. The recent availability of an IR array detector that can acquire 4096x4096 pixels of data at 7 m resolution offers the potential for data acquisition at 1000 times that of the conventional IR microscope at a much higher spatial resolution. In order to increase the efficiency of data acquisition on projects that already are using FTIR Microspectroscopy and to develop and validate new parameters which previously could not be obtained without the array detector, the IR Imaging Core requests funds to establish the core around the newly acquired FTS 6000 Stingray Infrared Microimaging System. On-going studies that will benefit from this instrumentation address specific questions about mineralized and non-mineralized connective tissues important to the study of bone development. These include how lipid phases change in the stratum corneum, how altered expression of non- collagenous matrix proteins affect bone mineral content and mineral properties, which is the effect of similar modification on the mineral and matrix formed in chondrocyte cultures, how does IL-6 affect bone mineral properties in vitro and in vivo, what are the mineral and matrix characteristics around loaded and unleaded osteocytes, how does the mineral changes as microdamage propagates, how does osteoarthritis alter bone mineral and matrix properties in a mouse model, what is the origin of bone fragility in osteogenesis imperfecta, and what are the changes in mineral and matrix that occur in osteoporosis and are they corrected by treatment with various therapeutic modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF A TREATMENT FOR OSTEOGENESIS IMPERFECTA Principal Investigator & Institution: Martin, R. Bruce.; Professor and Director; Orthopaedic Surgery; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 15-JUL-2000; Project End 30-JUN-2004 Summary: The goal of this study is to use an animal model to test a method for treating a class of bone diseases known as osteogenesis imperfecta (OI). In these disorders, the patient has one of numerous possible mutations in the genes that code for Type l collagen. This results in the production of abnormal Type l collagen molecules, or

12


insufficient amounts of this structural protein, or both. In any case, there can be substantial weakening of the patient's bone tissue. This leads to fractures caused by (1) the weakened bone material, and (2) excessive porosity produced by the bone's attempt to repair itself by remodeling. OI patients can only be cured through correction of their genome, a prospect on the horizon but unlikely to affect many patients soon. In the meantime, we propose that substantial amelioration of this disease can be achieved in children by controlling the bone modeling and remodeling processes so as to compensate for, and restrain negative responses to, the collagen defect. The agent we propose to use for this purpose is alendronate, a bisphosphonate that blocks bone resorption. This drug could benefit the juvenile OI patients by blocking the normal resorptive process on the metaphyseal surfaces of the patient's long bones, resulting in larger bones that compensate for the weak material within the cortex. Unfortunately, however, it is also possible that alendronate could interfere with the growth of the patient and produce negative as well as positive effects in terms of skeletal development. The specific aims are to 1) use the oim transgenic mouse model to test this method of treatment and elucidate its mechanisms in detail, and 2) determine whether the use of alendronate in children will have negative effects of their growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFICATION OF OSTEOGENIC PROGENITOR CELLS IN SKELET* Principal Investigator & Institution: Goldhamer, David J.; Associate Professor; Molecular and Cell Biology; University of Connecticut Storrs Unit 1133 StorrsMansfield, Ct 06269 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Cell-based therapies are emerging as a potentially powerful treatment for osteogenesis imperfecta, a genetic skeletal disorder characterized by bone fragility and deformities caused by defects in type I collagen. 0steogenic progenitor cells of possible therapeutic utility exist in skeletal muscle tissue, although their identity is unknown. In the present proposal, in vivo bone induction assays in mice will be used in conjunction with Cre/lox lineage tracing to definitively establish the osteogenic potential of five candidate cell types resident in skeletal muscle tissue: quiescent and activated muscle satellite cells, vascular smooth muscle (VSM) cells, pericytes and endothelial cells. Each cell type will be specifically and permanently labeled with lacZ by intercrossing two mouse strains: transgenic mice that express the gene for Cre recombinase under the control of a cell type-specific promoter/enhancer (MyoD-cre for satellite cells, smooth muscle myosin heavy chain-cre for VSM and pericytes, and Tie2-cre for endothelium) and Rosa26 Cre reporter mice, in which LacZ expression is Cre-dependent. The osteogenic potential of these cell types will be determined by following their fate after intramuscular injection of purified bone morphogenetic protein 2, which induces a robust osteogenic response that recapitulates normal endochondral bone formation. Cellular contributions to cartilage and bone will be determined by 0-galactosidase histochernistry and immunohistochemistry using cellspecific markers. In addition, the genetic control of satellite cell commitment and osteoinduction will be explored by assessing the osteogenic potential of satellite cells in mice carrying a null mutation in the muscle regulatory gene, MyoD. Finally, the osteogenic potential of muscle side population (SP) stem cells-recently identified by FACS analysis-will be evaluated in cell culture, and their relationship to satellite cells, VSM, pericytes and endothelium will be determined by combining lineage marking with FACS analysis of muscle-derived cells. Establishing the identity of osteogenic

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progenitor cells of skeletal muscle will provide the foundation for investigating mechanisms regulating commitment to the osteogenic lineage. Evaluating these osteoprogenitor cells in future cell transplantation models will provide an essential preclinical test of their utility for the treatment of osteogenesis imperfecta and other diseases of the musculoskeletal system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MARROW STROMAL CELLS FOR LYSOSOMAL DISEASE CNS DEFECTS Principal Investigator & Institution: Phinney, Donald G.; Assistant Professor; Center for Gene Therapy; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Resident in adult bone marrow is a cell population referred to as marrow stromal cells (MSCs) that possess several unique properties. First, MSCs mediate various aspects of hematopoiesis by expressing matrix molecules, cytokines and cell-surface receptors that provide architecture to the hematopoietic organ, support granulopoiesis and lymphopoiesis, and maintain the multi-potency of the hematopoietic stem cell. Second, MSCs are also able to differentiate into a variety of mesenchymal cell lineages, including osteoblasts and chondrocytes, suggesting the cells participate in most aspects of bone growth and repair. Accordingly, the potential of MSCs as cell and/or gene therapy vectors for the treatment of connective tissue diseases is being intensively studied. Such efforts have culminated in the first human clinical trial using MSCs to treat Osteogenesis Imperfecta. While the relevance of using MSCs to treat connective tissue diseases is obvious, our recent data regarding intracranial transplantation of MSCs suggests the cells may be useful vectors to treat central nervous system (CNS) disorders, as well. We recently showed that following injection into neonatal mouse brains, murine MSCs undergo marked expansion, migrate along established white matter tracts throughout successive layers of the brain, and at a low frequency adopt glial and possibly neuronal cell fates. Therefore, MSCs respond to the microenvironment of the developing brain in a manner similar to neural progenitor cells. To explore this potential of MSCs further, we propose to compare and contrast the engraftment, proliferation, migration, and differentiation of MSCs following injection into embryonic, neonatal, or adult brain with particular emphasis on 1) quantitating the number of MSCs that persist in brain as a function of time, 2) mapping their anatomical locations, and 3) characterizing their phenotype. By analyzing how brain development affects MSC engraftment, we can optimize a transplantation regimen that translates into an effective clinical strategy for using MSCs to treat CNS disorders. To directly assess the therapeutic potential of MSCs, we will transplant the cells into the brains of mice afflicted with Mucopolysaccharidosis Type VII, which exhibit progressive CNS neurodegeneration. These experiments will be conducted in a maimer so that they provide a basis for using a patients own MSCs to treat disorders affecting the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MARROW STROMAL CELLS IN OSTEOGENESIS IMPERFECTA MODEL Principal Investigator & Institution: Pochampally, Radhika R.; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 05-AUG-2002

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Summary: (provided by applicant): Osteogenesis Imperfecta (OI) that has an incidence of 1/10,000 - 1/20,000 live births, has frequently served as a model disorder for dominant negative conditions of structural proteins. Effective therapy for these disorders will require direct or targeted replacement of a mutated gene with wild-type allele. This research proposal will explore the possibility that patients with OI can potentially be treated with their own osteoprogenitors by gene-engineering the cells from their bone marrow that are referred to as mesenchymal stem cells or marrow stromal cells (MSCs). The marrow stromal cells will be used to test the hypothesis that marrow stromal cells from the patients with OI can be gene-engineered to correct the deleterious effects of mutations in type I collagen that produce the disease. The Specific Aims for this proposal are: (1) To obtain homologous recombination of the COL1A1 gene in human MSCs to determine the possibility of alleviating the OI symptoms by replacing the mutant allele with wild type allele of COL1A1 (2) To obtain overexpression clones of hMSCs that express COL1A1 cDNA to determine the effect of ratio of wild-type to mutant COL1A1 protein (3) To study the repair potential and homing of gene engineered hMSCs; the repair potential of gene engineered MSCs will be determined by injecting the cells into the fracture model and control mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANICAL ENVIRONMENT IN MANDIBULAR DISTRACTION Principal Investigator & Institution: Herring, Susan W.; Professor & Acting Chair; Orthodontics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Distraction osteogenesis (DO) is a means to elongate bone by placing tensile loads on a healing osteotomy. Although DO has been used on the mandible for only a decade, the technique is already supplanting more traditional orthognathic procedures, especially for children. Despite the fact that DO uses mechanics to accomplish its goals, the actual mechanical environment is unknown. Functions such as mastication must place intermittent compressive or shearing strains on the distraction site. These strains, as well as the tensile strains produced by the distraction appliance, are of critical biological significance for the osteogenic process, but have never been measured. Using a well-established model for mandibular DO, the pig, we propose (Aim 1) to clarify the mechanical environment of the distraction site at the time of osteotomy, during distraction, and during consolidation by making direct measurements of strain using strain gages, digital ultrasonics and differential variable reluctance transducers. These studies will investigate the influence of appliance size, stability, and placement as well as the action of specific muscles and occlusal loads. Further, we will address a major concern of treating growing children by mandibular DO, whether the procedure adversely affects growth at the mandibular condylar by overloading the TMJ. Thus, we propose (Aim 2) to ascertain the impact of DO on TMJ mechanics and growth by performing strain gage measurements on the condylar neck and relating the findings to growth, as measured by mineral apposition rate and periosteal deformation. The mechanical environment of DO, particularly the stability of the distraction site, may affect the course of healing and the final result by influencing which cells are recruited, the rapidity with which they proliferate, and their eventual fate. Therefore, we propose (Aim 3) to relate the mechanical history of DO to the repair process by assessing the contributions of the periosteum, muscle connective tissue, and vascular system to the regenerate. This will be accomplished by pulse labeling of replicating cells during distraction, combined with an investigation of protein expression at the time of sacrifice. The most important contributions of this proposal

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will be the characterization of strain at the DO site under natural conditions, and the application of that information to understanding of how DO works on a cellular level and how it affects mandibular growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT AW

PATIENT

ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Dimeglio, Linda A.; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: This project forms the basis of a Clinical Associate Physician grant for Linda Anne DiMeglio, MD. It will be used as a supplement for the General Clinical Research Center (GCRC) at the Indiana University School of Medicine. The broad objective is to provide a five-year period of mentored support for Dr. DiMeglio to facilitate her development as an independent clinical investigator. The application includes both a systematic career development plan and a clinical research project. The career development plan includes: l) completion of the Indiana University GCRC Department of Medicine two year Clinical Investigator Training Enhancement Program, 2) completion of a Master's Degree Ln Public Health, and 3) careful mentorship by Munro Peacock, MD, Ora Pescovitz, MD, and other researcher physicians to foster Dr. DiMeglio's evolution into a productive and independent clinical research investigator. The clinical research proposal describes a study to evaluate the efficacy and safety of "Bisphosphonate Therapy for Osteogenesis Imperfecta (OI)." OI is a heritable disorder of collagen synthesis. Affected persons have low bone mineral density and experience multiple fractures and progressive bony deformity. In its most severe form, the disorder is lethal in infancy. To date, no effective therapy exists for this debilitating condition. Improyements in bone mineral density and in fracture rates in a small number of children treated with intravenous bisphosphonates have been reported. The efficacy of oral bisphosphonates has not been established. We will characterize the changes effected by oral bisphosphonate therapy and compare them to a regimen of intravenous bisphosphonate therapy in a group of children with OI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF OSTEOGENESIS IMPERFECTA Principal Investigator & Institution: Byers, Peter H.; Professor; Pathology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 05-JAN-1992; Project End 31-JUL-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUTATIONAL EFFECTS ON COLLAGEN'S STRUCTURE & STABILITY Principal Investigator & Institution: Klein, Teri E.; Senior Research Scientist; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 21-AUG-2000; Project End 30-JUN-2004 Summary: (Verbatim) Bioengineering integrates chemical, physical and mathematical sciences applied to biology and medicine. Advancements in the structural basis of disease and the design of novel biomaterials will be obtained using computational

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methods and principles from the above mentioned sciences. Inclusion of the analysis of sequence information (bioinformatics) allows for more direct studies at a molecular level of large biopolymers and fibril proteins such as collagen. The long-term goal of this proposal is to determine the structural, physical and energetic properties of biopolymers using computational chemistry methods including thermodynamic integration and molecular dynamics. An increased understanding of the underlying molecular structure of native and mutant collagen molecules will elucidate the abnormal behavior of altered collagen molecules. This proposal defines a computational approach for determining the major forces contributing to the stability of collagen. This information will provide a foundation for constructing an energetic-structural map of the triple-helical domain for collagen. This map will ultimately be used as a basis for a computational genetic screening protocol to predict the phenotype of Osteogenesis Imperfecta (OI), serve as the foundation for understanding other fibril collagenous genetic disorders, and provide the detailed molecular information required for the design of novel collagen-like biomaterials. The specific aims of this proposal are: (1) determine the major forces contributing to the stability of the collagen triple-helix by simulating the structural and energetic effects on homotrimer collagen-like peptides; (2) determine the disruption effects of helix registration for known mutations associated with Ehlers-Danlos Syndrome (EDS) by simulating the structural and energetic effects that a glycine substitution has on disulfide bridge formation in the homotrimer type III collagen fragments; (3) determine the energetic and structural effects of different substituents on a naturally occurring sequence and four glycine mutants for a type I collagen fragment; (4) determine the neighborhood effects and individual contributions of electrostatics including hydrogen bonds and conformational changes for the OI regional phenotype model; and (5) determine the correlation among the computed thermodynamic quantities, experimental and clinical data associated with a particular mutation in the triple helix. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NIH OSTEOPOROSIS & RELATED BONE DISEASES RESOURCE CENTER Principal Investigator & Institution: Dawson-Hughes, Bess V.; Professor of Medicine; National Osteoporosis Foundation 1232 22Nd St Nw Washington, Dc 20037 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Taken from the Application) In 1993, Congress issued a mandate to increase awareness and knowledge about osteoporosis and related bone diseases. In response, the leading national nonprofit organizations in the field, the National Osteoporosis Foundation (NOF), The Paget Foundation (PF), and the Osteogenesis Imperfecta Foundation (OIF), were selected to establish the first national resource center in the field. In 1997, with 28 million Americans diagnosed or at risk for osteoporosis, 1.5 million painful fractures, $14 billion in health care costs, and millions affected by Paget's disease, osteogenesis imperfecta, and other related bone diseases, Congress renewed the Center's mandate. NOF and its collaborating partners propose to broaden and expand the reach of the current NIH Osteoporosis and Related Bone Diseases National Resource Center. Aim 1 focuses on strengthening the Center's infrastructure and broadening its services. Under the guidance of an Advisory Council, specific tasks include expanding the acquisition of research information and inquiry services; promoting the Center to physician and public audiences through exhibits, public service announcements and other means; and widely disseminating information via Web sites and other electronic methods, a speaker's bureau, and print publications such as

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bibliographies, fact sheets, and an expanded newsletter, to medical professionals, managed care organizations, and underserved and at-risk populations, including youth, men, and Hispanic and Asian American women. Aim 2 focuses on developing partnerships to create and evaluate a model education program to enhance bone health and reduce future risk of osteoporosis among a key group---adolescent females. The program will be based on a Center-sponsored communications study of the delivery of health promotion messages to this audience. Aim 3 is intended to expand awareness and use of research data. Specific efforts include supporting the National Osteoporosis Data Group, collecting and disseminating definitive statistics on bone diseases and on conditions co-morbid with osteoporosis, and preparing summary reports. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOGENESIS DACHSHUNDS

IMPERFECTA

TYPE

II

IN

WIREHAIRED

Principal Investigator & Institution: Giger, Urs; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: SUBPROJECT ABSTRACT NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPROGENITORS FOR POTENTIAL THERAPY OF OI Principal Investigator & Institution: Prockop, Darwin J.; Professor; Center for Gene Therapy; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 21-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): This proposal will explore the possibility that patients with osteogenesis imperfecta (OI) can potentially be treated with their own osteoprogenitors by gene-engineening the cells from their bone marrow that are referred to as mesenchymal stem cells or marrow stromal cells (MSCs). We will use antibodies to surface epitopes we have recently identified to prepare clonal and homogeneous preparations of the earliest progenitors in cultures of MSCs that have an enhanced ability to undergo multilineage differentiation and that are rapidly self-renewing cells (RS cells). The RS cells will be used to test the hypothesis that they are similar to CD34 positive stem cells used for bone marrow transplants and that therefore they will be the most effective cells to provide long-term engraftment of osteoprogenitors into bone. We will also test the hypothesis that RS cells from patients with OI can be gene-engineered to correct the deleterious effect, of mutations in type I Collagen that produce the disease. The Specific Aims are (1) Use a series of antibodies to surface epitopes we have recently identified to prepare clonal and homogeneous preparation, of RS cells from cultures of human MSCs. In the process, test the hypothesis that RS cells can be further fractionated to obtain homogeneous preparations of stem cells that are even more effective as osteoprogenitors for engrafment into bone. (2) Define the osteogenic potential in vitro of the RS cell preparations by assays of the rates of mineralization and assays of expressed genes by mRNA microarrays and proteomics. (3) Determine the osteogenic potential in vivo of the RS cell preparations by assays of differentiation into bone after subcutaneous implantation in vehicles or after systemic infusion into immunodeficient mice. (4) Determine the feasibility of correcting the gene defect in a patients own RS cells, (a) by overexpression of a cDNA for the wildtype COL I A I gene, or (b) by replacing a mutated COLlAl gene by homologous recombination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PAMIDRONATE IN CHILDREN W/ MODERATE TO SEVERE OSTEOGENESIS IMPERFECTA Principal Investigator & Institution: Warman, Matthew L.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: We propose to conduct an explanatory open study of cyclical intravenous pamidronate administration in children with moderate to severe OI to test the hypotheses that pamidronate will 1) significantly increase bone mass 2) reduce chronic bone pain 3) reduce the overall level of disability and 4) reduce disease activity assessed biochemically and histomorphometrically. The principal outcome measures to be assessed will be: 1) lumber spine and femoral neck bone mineral content and bone mineral density. 2) fracture rate and pain. 3) biochemical parameters of bone formation/resorption. 4) bone histomorphometry. 5) disability evaluation. 6) evidence of restoration of vertebral morphometry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTITATIVE MICROTOMOGRAPHY OF BONE TRABECULAE Principal Investigator & Institution: Flynn, Michael J.; Bioscience Professor; Radiation Oncology; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp046 Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): X-ray computed tomography of the spine and hip is an established method for quantitative bone mineral measurement that resolves elements with 1-millimeter size. For bone specimens, high-resolution laboratory computed tomography systems can describe cancellous bone architecture with resolved elements of about 50 micrometers. This is sufficient to describe bone volume, trabecular thickness and orientation, and connectivity. We have recently developed a new innovative method to perform quantitative computed tomography on an individual bone trabecula with resolved elements of 1 micrometer. Whole trabeculae are separated from cancellous bone specimens and scanned in a 250 micrometer diameter saline filled tube. A beam of x-rays from a synchrotron source is focused using a zone plate and used to make numerous measurements of radiation transmission. The measured data is then reconstructed to a 600 x 600 x 540 array of values having a spacing of 1/3 micrometers in the X, Y, and Z direction. High speed scanning devices will be used on this project to enable examination of 16 specimens per day. This method should be extremely valuable for evaluating the microscopic properties of bone tissue with respect to the mineralization of the matrix and porosity associated with osteocyte lacunae. To establish this value, four biomedical experiments are proposed for which genetic, pharmacologic, and biomechanic variables will be used to alter the bone tissue in animals. Prior experience indicates that these models should alter the mineralization and porosity at a microscopic scale. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REMODELIN, A NOVEL VASCULAR INJURY AND BONE RELATED GENE Principal Investigator & Institution: Lindner, Volkhard; Adjunct Professor; Maine Medical Center 22 Bramhall St Portland, Me 04102 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007

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Summary: (provided by applicant): With the intention of identifying novel genes involved in the arterial response to injury we undertook a differential screen of genes expressed in normal and injured arteries. We identified a novel sequence that with the exception of bone was not expressed in normal tissues, but highly induced in injured arteries. This cDNA contained an open reading frame of 245 amino acids with no significant homology to any known protein with the exception of a 36 amino acid (aa) long domain with 59% homology to the helical repeat regions found in collagens. Comparison with the human cDNA revealed 98% identity at the amino acid level indicative of a highly conserved protein. Northern blotting of mRNA derived from various adult rat organs revealed significant levels of this mRNA only in bone and lung. In balloon-injured arteries expression of this mRNA was prominent in adventitial fibroblasts during the proliferative and remodeling phase and only little expression was seen in smooth muscle cells of the developing neointima. Bone showed expression in the matrix of resting, proliferating and hypertrophic chondrocytes but expression was lost from the matrix as chondrocytes reached the apoptotic zone of the growth plate. Expression was also observed in periosteal cells. Based on its expression pattern, we named the gene remodelin. Several findings indicate that remode!in has important biological functions particularly in the arterial response to injury as well as in bone and cartilage matrix formation. These include: 1) increased remodulin expression in vitro is associated with decreased TGF-Beta expression as well as reduced TGF-Beta dependent gene expression (collagens type I and III), 2) increased remodulin expression in vivo results in phenotypes reminiscent of collagen mutants found in osteogenesis imperlecta (01), dystrophic epidermolysis bultosa (DEB) and myopathies (Bethlem), 3) in the absence of remodelin, expression of bone differentiation markers such as osteopontin and alkaline phosphatase (ALP) are dramatically increased, and 4) inhibition of Cbfa1 dependent gene expression such as osteocalcin by remodeiin. As such, remodelin appears to be an in vivo regulator of skeletal tissues and wound healing responses, potentially influencing calcification and differentiation along the chondrocyte/osteoblast lineages. As a potential inhibitor of calcification in the vessel wall this proposal will examine the role of remodelin in vascular calcification and remodeling using both in vitro and in vivo approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECOND HARMONIC GENERATION IMAGING MICROSCOPY Principal Investigator & Institution: Campagnola, Paul J.; Assistant Professor; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Type I collagen is the most abundant extra-cellular matrix protein being the primary structural component of bone, skin tendon and to a lesser extent blood vessels. Although its biochemical and ultrastructural properties are well understood, there are still gaps in our knowledge the precludes genotype/phenotype predictions in diseases affecting its primary structure or its gene regulation. This proposal will evaluate a new method for visualizing extra-cellular matrix Type I collagen fibers in cell culture or in intact tissues in real time utilizing second harmonic generation (SHG) imaging microscopy. This is a new and novel imaging technique that can be used to probe endogenous structural proteins with high contrast without the need for exogenous labels. Furthermore, this method provides intrinsic 3-dimensionality and is ideal for intact tissues since samples (up to 1 mm) can be imaged in situ. This method provides resolution on the order of 500 nm and is ideal for probing higher-level organization of collagen fibrils and fibers. SHG imaging will allow the direct visualization of some of

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the physical properties of the collagen triple helices. Studying the organization of collagen fibrillar structure by SHG imaging will in fact complement existing ultrastructural (X-ray diffraction and electron microscopy) and non-imaging (NMR, CD) methods. The value of this approach will be assessed in two disease of type I collagen that are a consequence of either under accumulation (osteogenesis imperfecta, OI) or excessive accumulation (tight skin, Tsk) of type I fibers in bone or skin respectively. In both cases, the relationship between the underlying genetic abnormality and the severity of the disease is not understood and a unique insight into this relationship may come from this method. We will first establish quantitative measurements of the collagen fibers in the ECM of normal murine tissues by SHG where we will utilize both tissue culture cells, and as well as tissues and decalcified bones from wild type mice. This methodology may ultimately become a powerful clinical tool both in terms of predictive value of musculo-skeletal diseases as well as in the assessment of the efficacy of drug and gene therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEM CELL THERAPY FOR DISEASES OF BONE IN A MOUSE MODEL Principal Investigator & Institution: Niyibizi, Christopher; Associate Professor; Orthopaedic Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2006 Summary: The focus of the present proposal is to utilize a mouse model of osteogenesis imperfecta (oim) as a model system to evaluate the potential of the bone marrow derived mesenchymal stem cells (BMSCs) to engraft and participate in repair and regeneration of bone. The mouse has a natural occurring mutation that results in nonexpression of proa2(I) chains leading to the accumulation of al(I) homotrimers in tissues. The mouse exhibits osteopenia, cortical thinning and easy fracturing and is an excellent model for evaluating the potential of BMSCs as targets for the treatment of genetic and non-genetic diseases of bone. Recent clinical trial by Horwitz et al. using whole marrow in children with a severe form of OI, demonstrated that BMSCs may offer treatment options for O1. Therefore, the hypotheses to be tested are: BMSCs from normal donor mice administered systemically or locally into syngeneic recipient mice will engraft in the bones of the recipient mice, synthesize authentic bone extracellular matrix and contribute to the structural integrity of the host bone. The following specific aims will be used to test these hypotheses: 1) Demonstrate that the cells infused into oim mice will engraft in bone and in fracture sites created in oim mice 2) Demonstrate that the cells which engraft in bone differentiate into osteoblasts and synthesize the authentic bone extracellular matrix and 3) Demonstrate that the cells that engraft in bone contribute to the structural integrity of bone. To accomplish the above aims, BMSCs will be established from femurs and tibiae of normal donor mice and either marked with retroviruses expressing LacZ or GFP genes to aid in cell tracking or unmarked prior to infusion in oim mice. The fate of the infused cells will be tracked by following expression of the marker genes in tissue and by fluorescent in situ hybridization (fish). Differentiation of the transplanted cells into osteoblasts in vivo will be determined by co-localization of osteocalcin and marker genes and also by in situ hybridization. Synthesis of authentic extraceltular matrix by the infused cells will be analyzed by the determination of the presence of type I collagen comprised of 1 and 2 heterotrimers. Structural integrity of the host bone, will be determined by histophotometry, crosslinking, and collagen content and bone mineral density. The proposed studies may lead

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to the development of better treatments for genetic and non-genetic diseases of bone based on BMSCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF COLLAGEN FIBRILS BY NMR Principal Investigator & Institution: Wittebort, Richard J.; Professor; Chemistry; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2000; Project Start 01-SEP-1992; Project End 31-MAR-2004 Summary: Our overall aim is to apply solid state NMR to oriented collagen fibrils, nature~s most abundant protein and to develop this technique for studying fibrous proteins and other macromolecular structures not amenable to x-ray diffraction or solution NMR methods. We propose to use solid state 2H, 13C and 15N NMR spectroscopy of collagen fibrils to directly determine essential elements of this important protein~s secondary structure. These studies make use of oriented fiber and magic angle spinning (MAS) methods. Structural features to be determined are the average orientation of individual peptide planes of the collagen tripeptide repeat relative to e fiber axis and the location of structural waters. The measurement and interpretation of 13C, 17O and 15N chemical shift parameters will be further developed with regard to a general method for determining secondary structure in solid proteins. Collagen provides the proteinaceous matrix for bone, it is the dominant material in and responsible for the tensile strength of tendons and it maintains the structural integrity of veins and arteries. In more than 90% of the cases of children with the heritable disorder of osteogenesis imperfecta, there is a mutation in the genes for type I procollagen. Clini l symptoms include extreme bone fragility, hypermobility and congenital dislocation of joints, osteoarthritis, osteoporosis and skin abnormalities. The architecture of the supramolecular collagen assembly is particularly sensitive to mutations which disrupt the structure of the collagen molecule anywhere along its 3000 A length, thus the collagen molecular structure is fundamental. We anticipate that these experiments will define the range of conformations that are allowed in the collagen triple helical motif. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL STUDIES OF TRIPLE-HELICAL PROTEINS Principal Investigator & Institution: Brodsky, Barbara M.; Professor; Biochemistry; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2003; Project Start 01-MAR-1977; Project End 31-AUG-2007 Summary: A peptide approach to a comprehensive understanding of the effect of amino acid sequence (Gly-X-Y)n on the stability, conformation, folding, dynamics and selfassociation of the normal and mutant collagen triple-helix is in progress. Our goals are to complete sequence-stability correlations at the molecular level; to develop peptides to model triple-helix self-association; and to pursue the disruption caused by Gly substitutions found in collagen diseases. Previous host-guest peptide studies established the triple-helix propensities of all 20 amino acids for the X and Y positions, and evaluation of molecular interactions within the triple-helix will be completed. These relationships between Gly-X-Y sequence and stability will be used to formulate predictions for the global stability of collagen model peptides and to relate local stability variations along collagen with ligand binding sites, microunfolding implicated in fibril formation, and the clinical severity of mutations. Calorimetric investigations are proposed to elaborate the mechanism of hydroxyproline stabilization of the triple-helix,

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and studies are proposed to further investigate the recently established sequence related modulation of triple-helix twist. An important goal is to establish a peptide system to model the self-association of triple-helices, since collagens function in supramolecular assemblies and some collagen mutations are pathological because of their influence on higher order structure. Strategies to design self-associating peptides will include pairs of oppositely charged residues to promote in register arrays and adaptation of sticky end and repeating pattern designs to form staggered arrays. Studies are proposed on peptide models of type I collagen mutations leading to a bone disease (osteogenesis imperfecta) and of type VII collagen mutations leading to a blistering skin disease (dystrophoic form of epidermolysis bullosa). The effect of the immediate sequence environment of the mutation and the identity of the residue replacing the Gly will be examined. Placing collagen structure, dynamics, and folding in a solid physicochemical framework through peptide studies will provide a context for understanding normal biological activities of selfassociation and binding, and for the changes occurring in many diseases affected by this abundant protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED PROGENITOR CELL ENGRAFTMENT Principal Investigator & Institution: Caplan, Arnold I.; Professor; Biology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 21-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Bone marrow contains mesenchymal progenitor cells that we have called mesenchymal stem cells (MSCs). The MSCs have been shown to have the capacity to differentiate into a variety of unique mesenchyrnal tissues including bone, cartilage, muscle, fat, tendon, marrow stroma, and other connective tissues. Osteogenesis Imperfecta (OI) is a disease that is caused by mutations in the type I collagen gene. One of the progeny of MSCs, the osteoblast, is responsible for fabricating bone and, thus, a mutation in the type I collagen gene can result in bone with physical and mechanical properties that are compromised depending on the exact location and extent of the mutation. One possible curative therapy for OI is to transplant and optimize the engraftment of allogenic MSCs whose type I collagen genes are normal. As a first step to develop a procedure for effectively delivering genetically normal progenitor cells to bone for a variety of NEW therapeutic purposes, including OI, a new cell targeting strategy has been developed. The progenitor cells are modified by non-genetic insertion of macromolecules containing tissue addresses that transiently occupy positions on the outer most surface of the cell. The addition of these addressing macromolecules has been called CELL PAINTING. A newly developed, simple Cell Painting technology involves coating cells with palmitated Protein-A and then exposing these cells to a fusion protein containing the Protein A-binding FC portion of antibodies and a tissue targeting peptide. These tissue targeting peptide address assemblies are removed from the cell surface by normal mechanisms of membrane turnover within 48 to 72 hours and are thus, harmless in a long-term sense. The Objective of the research proposed here is to optimize the Cell Painting technology and to identify the most effective bone- or bone-marrow-specific addressing peptides to optimize engraftment. The HYPOTHESIS that we will focus our experimentation on is that marrow derived mesenchyrnal progenitor cells delivered back to the marrow in a specific and effective manner will engraft in sufficient numbers to effect the bone physiology of the hosts and provide a curative therapy for OI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OF OSTEOPENIA IN CHILDREN WITH CEREBRAL PALSY Principal Investigator & Institution: Henderson, Richard C.; Professor; Orthopaedics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 29-SEP-2004 Summary: (provided by applicant): Osteopenia resulting in fractures with minimal trauma is a common problem in many pediatric conditions such as osteogenesis imperfecta, juvenile idiopathic osteoporosis, muscular dystrophy, and myelodysplasia (spina bifida). As part of the North American Growth in Cerebral Palsy Project (NAGCePP) we have extensively studied one such group of children, those with cerebral palsy (CP), to better define the prevalence, causes, and consequences of osteopenia in this condition. Bisphosphonates are a group of medications utilized to treat osteoporosis in elderly adults. There are published reports of these agents used in assorted pediatric conditions, but with rare exception these are anecdotal, uncontrolled case reports involving at most a few children. We have recently completed a small placebo-controlled Pilot Trial to assess the safety and efficacy of intravenous bisphosphonates to treat low bone density in children with severe CP. At the conclusion of the 18-month study period bone density in the distal femur had increased 89% + 21% (mean + SE) compared to 9% + 6% in controls. No clinically significant adverse effects were identified. The Pilot Trial raises many questions with regards to dosing (frequency, duration, amount, route of administration), indications for treatment, long-term risks and benefits including the effect on fracture rate. The results of the Pilot Trial provide the justification for a larger scale Future Clinical Trial to answer these many questions. The purpose of this application is to support the Clinical Trial Planning Project, a process critical to the successful implementation and completion of the Future Clinical Trial. The Clinical Trial Planning Project will focus on building from both the Pilot Trial and the existing NAGCeP collaboration in several areas. Subjects: Develop additional recruiting strategies for larger numbers of subjects and further refine criteria for inclusion based on analysis of fracture risk data. Intervention: Select alternative drugs and dosing regimens that are more practical. Outcomes: Further evaluate and adapt DXA technology to this population with contractures, scoliosis, metallic implants, involuntary muscle spasms, retardation, and other characteristics that present unique challenges. Collaborative Resources & Infrastructure: Adapt and expand our existing NAGCePP network (eg database, safety monitoring) to incorporate the Future Clinical Trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: USE OF HAMMERHEAD RIBOZYMES IN MURINE MODELS OF OL Principal Investigator & Institution: Wenstrup, Richard J.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The overall goal of these studies is to test the ability of self-cleaving multimeric ribozyme constructs to ameliorate phenotypic features of osteogenesis imperfecta (OI). We propose that the dominant-negative effect of "structural" or non-excluded type I collagen mutations associated with the most severe forms of OI must be taken into account in all strategies aimed at correcting the collagen defects in those patients, and that elimination of mutant alleles must be highly efficient, since even low levels of mutant allelic products can have a major deleterious effect.

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Experiments described in this proposal are designed to advance our development of ribozyme genes that effectively target type I collagen mutations typically observed in severe OI patients. In particular, self-cleaving multimeric ribozyme expressing genes will be designed and tested. These may provide sufficiently high ribozyme delivery to target cells so that a greater degree of allelic selectivity can be designed into ribozyme subunits that would ultimately be targeted against heterozygous single nucleotide substitutions. Experiments described in this proposal include: (1) design and testing of self-cleaving multimeric hammerhead ribozyme(s) that selectively cleave adjacent to a unique deletion junction in the human proa1(I) collagen minigene pMG155. Preliminary testing of the ribozymes' efficiency will be performed by RNase protection in vitro. Target constructs will be stably expressed in MC3T3-E1 cells for in cellulo ribozyme testing. Cleavage efficacy and reversal of a well-defined biochemical phenotype in minigene-expressing MC3T3-E1 cells will be demonstrated by Northern and Western blot analysis, pulse-chase labeling of procollagens, and measurement of several markers of cellular differentiation. Transgenic mice that express either pMG155 or the most optimal multimeric ribozyme expression gene will be mated, and the phenotypes of doubly transgenic mice will be compared to those of mice expressing only the target sequence or the ribozyme; (2) similar in vitro, in cellulo, and in vivo testing will be performed on multimeric ribozymes, that target glycine mutations created in modified versions pMG155 containing an in-frame, 270 bp eDNA segment from the 3' end of the triple helical domain of the murine colla2 gene; and (3) we will test possible additive therapeutic benefits of targeting a potential downstream mediator of the OI dominant negative phenotype, osteocalcin, in mice transgenic for a collagen minigene and optimal ribozyme construct targeting both the minigene and osteocalcin. 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 “osteogenesis imperfecta” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for osteogenesis imperfecta in the PubMed Central database: •

A defect in the structure of type I procollagen in a patient who had osteogenesis imperfecta: excess mannose in the COOH-terminal propeptide. by Peltonen L, Palotie A, Prockop DJ.; 1980 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350238

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Defective Pro[alpha]2(I) Collagen Synthesis in a Recessive Mutation in Mice: A Model of Human Osteogenesis Imperfecta. by Chipman SD, Sweet HO, McBride DJ Jr,

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

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

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Davisson MT, Marks SC Jr, Shuldiner AR, Wenstrup RJ, Rowe DW, Shapiro JR.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45947 •

Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. by Beck K, Chan VC, Shenoy N, Kirkpatrick A, Ramshaw JA, Brodsky B.; 2000 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18226

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Hammerhead ribozymes selectively suppress mutant type I collagen mRNA in osteogenesis imperfecta fibroblasts. by Dawson PA, Marini JC.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110781

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Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. by Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124401

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Left ventricular rupture after mitral valve replacement in a patient with osteogenesis imperfecta tarda. by Lijoi A, Cisico S, Caputo E, Scarano F, Parodi E, Passerone GC.; 1999; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325668

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Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. by Pereira RF, O'Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ.; 1998 Feb 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18700

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Modeling the benefits of pamidronate in children with osteogenesis imperfecta. by Lindsay R.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151622

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Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta. by Spotila LD, Constantinou CD, Sereda L, Ganguly A, Riggs BL, Prockop DJ.; 1991 Jun 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51885

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Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta. by Barsh GS, Byers PH.; 1981 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320349

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The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. by Rauch F, Travers R, Plotkin H, Glorieux FH.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151613

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Thermal stability of type I and type III procollagens from normal human fibroblasts and from a patient with osteogenesis imperfecta. by Peltonen L, Palotie A, Hayashi T, Prockop DJ.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348228

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Transgenic Mouse Model of the Mild Dominant Form of Osteogenesis Imperfecta. by Bonadio J, Saunders TL, Tsai E, Goldstein SA, Morris-Wiman J, Brinkley L, Dolan DF, Altschuler RA, Hawkins JE Jr, Bateman JF, Mascara T, Jaenisch R.; 1990 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54700

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Type I osteogenesis imperfecta: a nonfunctional allele for pro alpha 1 (I) chains of type I procollagen. by Barsh GS, David KE, Byers PH.; 1982 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346523

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

A case of chondrodysplasia punctata with features of osteogenesis imperfecta type II. Author(s): Sidden CR, Filly RA, Norton ME, Kostiner DR. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2001 June; 20(6): 699-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11400945

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A novel Gly to Arg substitution at position 388 of the alpha1 chain of type I collagen in lethal form of osteogenesis imperfecta. Author(s): Galicka A, Wolczynski S, Lesniewicz R, Chyczewski L, Gindzienski A. Source: Acta Biochimica Polonica. 2002; 49(2): 443-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362986

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

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A search for calcium, magnesium and zinc levels in fingernails of 135 patients with osteogenesis imperfecta. Author(s): Karita K, Takano T, Nakamura S, Haga N, Iwaya T. Source: Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (Gms). 2001; 15(1): 36-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11603825

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A single amino acid substitution (D1441Y) in the carboxyl-terminal propeptide of the proalpha1(I) chain of type I collagen results in a lethal variant of osteogenesis imperfecta with features of dense bone diseases. Author(s): Pace JM, Chitayat D, Atkinson M, Wilcox WR, Schwarze U, Byers PH. Source: Journal of Medical Genetics. 2002 January; 39(1): 23-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826020

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A variant of osteogenesis imperfecta type IV with resolving kyphomelia is caused by a novel COL1A2 mutation. Author(s): Johnson MT, Morrison S, Heeger S, Mooney S, Byers PH, Robin NH. Source: Journal of Medical Genetics. 2002 February; 39(2): 128-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836364

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Abnormal mineral composition of osteogenesis imperfecta bone as determined by electron probe X-ray microanalysis on conventional and cryosections. Author(s): Sarathchandra P, Kayser MV, Ali SY. Source: Calcified Tissue International. 1999 July; 65(1): 11-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10369727

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Abnormalities in central nervous system development in osteogenesis imperfecta type II. Author(s): Emery SC, Karpinski NC, Hansen L, Masliah E. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 1999 March-April; 2(2): 124-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9949218

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Abnormalities in the cerebral arterial system in osteogenesis imperfecta. Author(s): Albayram S, Kizilkilic O, Yilmaz H, Tuysuz B, Kocer N, Islak C. Source: Ajnr. American Journal of Neuroradiology. 2003 April; 24(4): 748-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695216

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Acetabular protrusion in osteogenesis imperfecta. Author(s): Violas P, Fassier F, Hamdy R, Duhaime M, Glorieux FH. Source: Journal of Pediatric Orthopedics. 2002 September-October; 22(5): 622-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198464

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Advances in osteogenesis imperfecta. Author(s): Cole WG. Source: Clinical Orthopaedics and Related Research. 2002 August; (401): 6-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151877

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Age-related changes in human bone proteoglycan structure. Impact of osteogenesis imperfecta. Author(s): Grzesik WJ, Frazier CR, Shapiro JR, Sponseller PD, Robey PG, Fedarko NS. Source: The Journal of Biological Chemistry. 2002 November 15; 277(46): 43638-47. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221073

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Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model. Author(s): McCarthy EA, Raggio CL, Hossack MD, Miller EA, Jain S, Boskey AL, Camacho NP. Source: Pediatric Research. 2002 November; 52(5): 660-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409511

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An alpha2(I) glycine to aspartate substitution is responsible for the presence of a kink in type I collagen in a lethal case of osteogenesis imperfecta. Author(s): Forlino A, Keene DR, Schmidt K, Marini JC. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 1998 December; 17(8-9): 575-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9923651

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An incomplete form of the Fanconi syndrome in a patient with osteogenesis imperfecta. Author(s): Oktenli C, Bulucu F, Koc B, Alis M. Source: Clinical Nephrology. 2001 February; 55(2): 175. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11269684

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Anthropometry of patients with osteogenesis imperfecta. Author(s): Lund AM, Muller J, Skovby F. Source: Archives of Disease in Childhood. 1999 June; 80(6): 524-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332000

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Aortic valve replacement in a woman with osteogenesis imperfecta. Author(s): Aoki T, Kuraoka S, Ohtani S, Kuroda Y. Source: Ann Thorac Cardiovasc Surg. 2002 February; 8(1): 51-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916445

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Aortic valve surgery in osteogenesis imperfecta: report of two cases and review of the literature. Author(s): Zegdi R, D'Attellis N, Fornes P, Fuzellier JF, Carteaux JP, Fabiani JN, Carpentier A. Source: J Heart Valve Dis. 1998 September; 7(5): 510-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9793847

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Aspects of the history of osteogenesis imperfecta (Vrolik's syndrome). Author(s): Baijet B. Source: Ann Anat. 2002 January; 184(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876477

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Assessment of dysplastic dentin in osteogenesis imperfecta and dentinogenesis imperfecta. Author(s): Malmgren B, Lindskog S. Source: Acta Odontologica Scandinavica. 2003 April; 61(2): 72-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12790503

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Association of COL1A1 and otosclerosis: evidence for a shared genetic etiology with mild osteogenesis imperfecta. Author(s): McKenna MJ, Kristiansen AG, Bartley ML, Rogus JJ, Haines JL. Source: The American Journal of Otology. 1998 September; 19(5): 604-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9752968

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Basilar impression complicating osteogenesis imperfecta type IV: the clinical and neuroradiological findings in four cases. Author(s): Hayes M, Parker G, Ell J, Sillence D. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 March; 66(3): 357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084535

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Basilar impression in osteogenesis imperfecta tarda. Case report. Author(s): Kurimoto M, Ohara S, Takaku A. Source: Journal of Neurosurgery. 1991 January; 74(1): 136-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1984494

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Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management. Author(s): Sawin PD, Menezes AH. Source: Journal of Neurosurgery. 1997 June; 86(6): 950-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9171173

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Beneficial effect of bisphosphonate during five years of treatment of severe osteogenesis imperfecta. Author(s): Astrom E, Soderhall S. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 January; 87(1): 64-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9510450

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Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta. Author(s): Astrom E, Soderhall S. Source: Archives of Disease in Childhood. 2002 May; 86(5): 356-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11970931

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Bilateral isolated olecranon fractures in an infant as presentation of osteogenesis imperfecta. Author(s): DiCesare PE, Sew-Hoy A, Krom W. Source: Orthopedics. 1992 June; 15(6): 741-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1608868

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Biochemical analysis of callus tissue in osteogenesis imperfecta type IV. Evidence for transient overmodification in collagen types I and III. Author(s): Brenner RE, Vetter U, Nerlich A, Worsdorfer O, Teller WM, Muller PK. Source: The Journal of Clinical Investigation. 1989 September; 84(3): 915-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2760218

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Bisphosphonate therapy for severe osteogenesis imperfecta. Author(s): Glorieux FH. Source: J Pediatr Endocrinol Metab. 2000 September; 13 Suppl 2: 989-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11086652

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Bisphosphonates in children with osteogenesis imperfecta may improve bone mineralization but not bone strength. Report of two patients. Author(s): Roldan EJ, Pasqualini T, Plantalech L. Source: J Pediatr Endocrinol Metab. 1999 July-August; 12(4): 555-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417973

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Bisphosphonates in osteogenesis imperfecta. Author(s): Shaw NJ. Source: Archives of Disease in Childhood. 1997 July; 77(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9279168

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Bone density measurement in osteogenesis imperfecta may well be important. Author(s): Paterson CR, Mole PA. Source: Postgraduate Medical Journal. 1995 February; 71(832): 124. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7724430

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Bone density measurements by computed tomography in osteogenesis imperfecta type I. Author(s): Miller ME, Hangartner TN. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 9(5): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10550462

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Bone fragility in transgenic mice expressing a mutated gene for type I procollagen (COL1A1) parallels the age-dependent phenotype of human osteogenesis imperfecta. Author(s): Pereira RF, Hume EL, Halford KW, Prockop DJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1995 December; 10(12): 1837-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8619363

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Bone graft augmentation and dental implant treatment in a patient with osteogenesis imperfecta: review of the literature with a case report. Author(s): Lee CY, Ertel SK. Source: Implant Dentistry. 2003; 12(4): 291-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752964

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Bone histomorphometry in adults with type IA osteogenesis imperfecta. Author(s): McCarthy EF, Earnest K, Rossiter K, Shapiro J. Source: Clinical Orthopaedics and Related Research. 1997 March; (336): 254-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9060512

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Bone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy. Author(s): Rauch F, Plotkin H, Zeitlin L, Glorieux FH. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 April; 18(4): 610-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12674321

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Bone mineral content and collagen defects in osteogenesis imperfecta. Author(s): Lund AM, Molgaard C, Muller J, Skovby F. Source: Acta Paediatrica (Oslo, Norway : 1992). 1999 October; 88(10): 1083-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565454

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Bone mineral density in children with mild osteogenesis imperfecta. Author(s): Zionts LE, Nash JP, Rude R, Ross T, Stott NS. Source: The Journal of Bone and Joint Surgery. British Volume. 1995 January; 77(1): 1437. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7822373

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Bone resorption assessed by immunoassay of urinary cross-linked collagen peptides in patients with osteogenesis imperfecta. Author(s): Minisola S, Rosso R, Romagnoli E. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1995 February; 10(2): 335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7754815

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Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): review and report on the first North American case. Author(s): McPherson E, Clemens M. Source: American Journal of Medical Genetics. 1997 May 2; 70(1): 28-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9129737

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Calcium kinetics in children with osteogenesis imperfecta type III and IV: pre- and post-growth hormone therapy. Author(s): Vieira NE, Goans RE, Weiss GH, Hopkins E, Marini JC, Yergey AL. Source: Calcified Tissue International. 2000 August; 67(2): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10920211

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Cardiac reoperation in a patient with osteogenesis imperfecta: a case report. Author(s): Iha K, Uehara T, Higa N, Akasaki M, Kuniyoshi Y, Koja K. Source: Ann Thorac Cardiovasc Surg. 2001 August; 7(4): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11578267

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Case 48: osteogenesis imperfecta of the temporal bone. Author(s): Heimert TL, Lin DD, Yousem DM. Source: Radiology. 2002 July; 224(1): 166-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091678

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Case report. Bilateral simultaneous patellar tendon ruptures associated with osteogenesis imperfecta. Author(s): Kothari P, Mohan N, Hunter JB, Kerslake R. Source: Annals of the Royal College of Surgeons of England. 1998 November; 80(6): 4168. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209412

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Central corneal thickness is lower in osteogenesis imperfecta and negatively correlates with the presence of blue sclera. Author(s): Evereklioglu C, Madenci E, Bayazit YA, Yilmaz K, Balat A, Bekir NA. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2002 November; 22(6): 511-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477015

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Changes in bone biochemical markers after high-dose cerivastatin treatment in a woman with osteogenesis imperfecta. Author(s): Sugiyama T, Kawai S. Source: Journal of Bone and Mineral Metabolism. 2001; 19(6): 382-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685655

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Chest compressions in an infant with osteogenesis imperfecta type II: No new rib fractures. Author(s): Sewell RD, Steinberg MA. Source: Pediatrics. 2000 November; 106(5): E71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061808

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Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Author(s): Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE, Brenner MK. Source: Blood. 2001 March 1; 97(5): 1227-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11222364

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Cochlear implantation in a child with osteogenesis imperfecta. Author(s): Migirov L, Henkin Y, Hildesheimer M, Kronenberg J. Source: International Journal of Pediatric Otorhinolaryngology. 2003 June; 67(6): 677-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745164

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Cochlear implantation in a patient with osteogenesis imperfecta and otospongiosis. Author(s): Huang TS, Yen PT, Liu SY. Source: American Journal of Otolaryngology. 1998 May-June; 19(3): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9617935

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Cochlear implantation in osteogenesis imperfecta. Author(s): Szilvassy J, Jori J, Czigner J, Toth F, Szilvassy Z, Kiss JG. Source: Acta Otorhinolaryngol Belg. 1998; 52(3): 253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9810462

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Co-existence of osteogenesis imperfecta and hyperparathyroidism. Author(s): Zimmermann-Belsing T, Lund AM, Christensen L, Feldt-Rasmussen U. Source: J Endocrinol Invest. 1999 July-August; 22(7): 547-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10475153

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Coexistence of supravalvular aortic stenosis and osteogenesis imperfecta. Author(s): McGlinchey PG, Spence MS, McKeown PP, Mulholland HC, Khan MM. Source: Ulster Med J. 2001 November; 70(2): 155-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11795769

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COL1A1 mutation analysis in Lithuanian patients with osteogenesis imperfecta. Author(s): Benusiene E, Kucinskas V. Source: Journal of Applied Genetics. 2003; 44(1): 95-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590186

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Collagen content and growth factor immunoexpression in uterine lower segment of type IA osteogenesis imperfecta: Relationship with recurrent uterine rupture in pregnancy. Author(s): Di Lieto A, Pollio F, De Falco M, Iannotti F, Mascolo M, Somma P, Staibano S. Source: American Journal of Obstetrics and Gynecology. 2003 August; 189(2): 594-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520241

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Collagen-derived markers of bone metabolism in osteogenesis imperfecta. Author(s): Lund AM, Hansen M, Kollerup G, Juul A, Teisner B, Skovby F. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 November; 87(11): 1131-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9846914

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Comparative studies of osteoblast and fibroblast type I collagen in a patient with osteogenesis imperfecta type IV. Author(s): Galicka A, Wolczynski S, Gindzienski A. Source: The Journal of Pathology. 2002 February; 196(2): 235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793376

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Complications of the Bailey-Dubow elongating nail in osteogenesis imperfecta: 34 children with 110 nails. Author(s): Janus GJ, Vanpaemel LA, Engelbert RH, Pruijs HE. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 1999 July; 8(3): 203-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10399125

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Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. Author(s): Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Source: The New England Journal of Medicine. 1998 October 1; 339(14): 947-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753709

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Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta. Author(s): Lee YS, Low SL, Lim LA, Loke KY. Source: European Journal of Pediatrics. 2001 November; 160(11): 641-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11760017

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Decreased bone mineral density in HLA-B27 positive members of a family with osteogenesis imperfecta. Author(s): Escalante A, Beardmore TD. Source: The Journal of Rheumatology. 1993 February; 20(2): 320-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8474070

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Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome). Author(s): Brenner RE, Vetter U, Stoss H, Muller PK, Teller WM. Source: European Journal of Pediatrics. 1993 June; 152(6): 505-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8335019

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Defects of type I procollagen metabolism correlated with decrease of prolidase activity in a case of lethal osteogenesis imperfecta. Author(s): Galicka A, Wolczynski S, Anchim T, Surazynski A, Lesniewicz R, Palka J. Source: European Journal of Biochemistry / Febs. 2001 April; 268(7): 2172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277941

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Deficient expression of the small proteoglycan decorin in a case of severe/lethal osteogenesis imperfecta. Author(s): Dyne KM, Valli M, Forlino A, Mottes M, Kresse H, Cetta G. Source: American Journal of Medical Genetics. 1996 May 3; 63(1): 161-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723103

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Deletion of 19 base pairs in intron 13 of the gene for the pro alpha 2(I) chain of type-I procollagen (COL1A2) causes exon skipping in a proband with type-I osteogenesis imperfecta. Author(s): Zhuang J, Tromp G, Kuivaniemi H, Nakayasu K, Prockop DJ. Source: Human Genetics. 1993 April; 91(3): 210-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7916744

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Deletion of a Gly-Pro-Pro repeat in the pro alpha2(I) chain of procollagen I in a family with dominant osteogenesis imperfecta type IV. Author(s): Lund AM, Skovby F, Schwartz M. Source: Human Genetics. 1996 March; 97(3): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786065

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Deletions and duplications of Gly-Xaa-Yaa triplet repeats in the triple helical domains of type I collagen chains disrupt helix formation and result in several types of osteogenesis imperfecta. Author(s): Pace JM, Atkinson M, Willing MC, Wallis G, Byers PH. Source: Human Mutation. 2001 October; 18(4): 319-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668615

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Dental aberrations in children and adolescents with osteogenesis imperfecta. Author(s): Malmgren B, Norgren S. Source: Acta Odontologica Scandinavica. 2002 March; 60(2): 65-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12020117

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Dental management of severe dentinogenesis imperfecta in a mild form of osteogenesis imperfecta. Author(s): Stephen LX, Beighton P. Source: J Clin Pediatr Dent. 2002 Winter; 26(2): 131-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11878277

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Dental manifestations of osteogenesis imperfecta and abnormalities of collagen I metabolism. Author(s): Lund AM, Jensen BL, Nielsen LA, Skovby F. Source: Journal of Craniofacial Genetics and Developmental Biology. 1998 JanuaryMarch; 18(1): 30-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9594376

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Dentinogenesis imperfecta associated with osteogenesis imperfecta: report of two cases. Author(s): Tsai CL, Lin YT, Lin YT. Source: Chang Gung Med J. 2003 February; 26(2): 138-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12718392

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Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. Author(s): Beck K, Chan VC, Shenoy N, Kirkpatrick A, Ramshaw JA, Brodsky B. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 April 11; 97(8): 4273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725403

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Determination of a new collagen type I alpha 2 gene point mutation which causes a Gly640 Cys substitution in osteogenesis imperfecta and prenatal diagnosis by DNA hybridisation. Author(s): Gomez-Lira M, Sangalli A, Pignatti PF, Digilio MC, Giannotti A, Carnevale E, Mottes M. Source: Journal of Medical Genetics. 1994 December; 31(12): 965-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7891382

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Differing lumbar vertebral mineralization rates in ambulatory pediatric patients with osteogenesis imperfecta. Author(s): Reinus WR, McAlister WH, Schranck F, Chines A, Whyte MP. Source: Calcified Tissue International. 1998 January; 62(1): 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9405727

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Direct sequencing of PCR products derived from cDNAs for the pro alpha 1 and pro alpha 2 chains of type I procollagen as a screening method to detect mutations in patients with osteogenesis imperfecta. Author(s): Zhuang J, Tromp G, Kuivaniemi H, Castells S, Bugge M, Prockop DJ. Source: Human Mutation. 1996; 7(2): 89-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8829649

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Direct sequencing of PCR products for mutation detection in osteogenesis imperfecta. Author(s): Galicka A, Gindzienski A. Source: Journal of Applied Genetics. 2002; 43(3): 365-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12177526

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Discrimination of morphological findings in dentine from osteogenesis imperfecta patients using combinations of polarized light microscopy, microradiography and scanning electron microscopy. Author(s): Lindau B, Dietz W, Lundgren T, Storhaug K, Noren JG. Source: International Journal of Paediatric Dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children. 1999 December; 9(4): 25361. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10815583

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Displaced fractures of the apophysis of the olecranon in children who have osteogenesis imperfecta. Author(s): Stott NS, Zionts LE. Source: The Journal of Bone and Joint Surgery. American Volume. 1993 July; 75(7): 102633. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8335662

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Disruption of one intra-chain disulphide bond in the carboxyl-terminal propeptide of the proalpha1(I) chain of type I procollagen permits slow assembly and secretion of overmodified, but stable procollagen trimers and results in mild osteogenesis imperfecta. Author(s): Pace JM, Kuslich CD, Willing MC, Byers PH. Source: Journal of Medical Genetics. 2001 July; 38(7): 443-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11432962

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Double valve replacement in a patient with osteogenesis imperfecta. Author(s): Chrysant GS, Cassivi SD, Carey CF, Sundt TM. Source: J Heart Valve Dis. 2002 September; 11(5): 751-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358415

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Early surgical management of severe forms of osteogenesis imperfecta. Author(s): Cole WG. Source: American Journal of Medical Genetics. 1993 January 15; 45(2): 270-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456817

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Effect of cyclical intravenous pamidronate therapy in children with osteogenesis imperfecta. Open-label study in seven patients. Author(s): Giraud F, Meunier PJ. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 October; 69(5): 486-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477233

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Effect of growth hormone treatment on calcium kinetics in patients with osteogenesis imperfecta type III and IV. Author(s): Vieira NE, Marini JC, Hopkins E, Abrams SA, Yergey AL. Source: Bone. 1999 October; 25(4): 501-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10511119

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Effect of long-term calcitonin therapy by injection and nasal spray on the incidence of fractures in osteogenesis imperfecta. Author(s): Nishi Y, Hamamoto K, Kajiyama M, Ono H, Kihara M, Jinno K. Source: The Journal of Pediatrics. 1992 September; 121(3): 477-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1517930

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Effect of lower limb Sofield procedure on ambulation in osteogenesis imperfecta. Author(s): Khoshhal KI, Ellis RD. Source: Journal of Pediatric Orthopedics. 2001 March-April; 21(2): 233-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11242257

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Effect of lower limb Sofield procedure on ambulation of osteogenesis imperfecta. Author(s): Wilkinson JM, Bell MJ. Source: Journal of Pediatric Orthopedics. 2002 March-April; 22(2): 274. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11856946

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Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. Author(s): Orioli IM, Castilla EE, Scarano G, Mastroiacovo P. Source: American Journal of Medical Genetics. 1995 November 6; 59(2): 209-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8588588

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Effect of rhBMP-2 on the osteogenic potential of bone marrow stromal cells from an osteogenesis imperfecta mouse (oim). Author(s): Balk ML, Bray J, Day C, Epperly M, Greenberger J, Evans CH, Niyibizi C. Source: Bone. 1997 July; 21(1): 7-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9213002

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Effects of transforming growth factor beta on cells derived from bone and callus of patients with osteogenesis imperfecta. Author(s): Morike M, Windsheimer E, Brenner R, Nerlich A, Bushart G, Teller W, Vetter U. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 1993 July; 11(4): 564-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8340828

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Effects of treatment with etidronate and alfacalcidol for osteogenesis imperfecta type I: a case report. Author(s): Iwamoto J, Matsu K, Takeda T, Ichimura S, Uzawa M. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(2): 243-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665966

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Effects of withdrawal of bracing in matched pairs of children with osteogenesis imperfecta. Author(s): Gerber LH, Binder H, Berry R, Siegel KL, Kim H, Weintrob J, Lee YJ, Mizell S, Marini J. Source: Archives of Physical Medicine and Rehabilitation. 1998 January; 79(1): 46-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9440417

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Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta. Author(s): Gonzalez E, Pavia C, Ros J, Villaronga M, Valls C, Escola J. Source: J Pediatr Endocrinol Metab. 2001 May; 14(5): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11393574

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Endoplasmic reticulum-mediated quality control of type I collagen production by cells from osteogenesis imperfecta patients with mutations in the pro alpha 1 (I) chain carboxyl-terminal propeptide which impair subunit assembly. Author(s): Lamande SR, Chessler SD, Golub SB, Byers PH, Chan D, Cole WG, Sillence DO, Bateman JF. Source: The Journal of Biological Chemistry. 1995 April 14; 270(15): 8642-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7721766

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Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta. Author(s): Marini JC, Bordenick S, Heavner G, Rose S, Chrousos GP. Source: American Journal of Medical Genetics. 1993 January 15; 45(2): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456815

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Evaluation of oral problems in an osteogenesis imperfecta population. Author(s): O'Connell AC, Marini JC. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1999 February; 87(2): 189-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10052375

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Excess paternal age in apparently sporadic osteogenesis imperfecta. Author(s): Blumsohn A, McAllion SJ, Paterson CR. Source: American Journal of Medical Genetics. 2001 May 15; 100(4): 280-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343319

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Experience with Bailey-Dubow rodding in children with osteogenesis imperfecta. Author(s): Karbowski A, Schwitalle M, Brenner R, Lehmann H, Pontz B, Worsdorfer O. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery. [et Al] = Zeitschrift Fur Kinderchirurgie. 2000 April; 10(2): 119-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10877081

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Extracellular matrix deposition in cultured dermal fibroblasts from four probands affected by osteogenesis imperfecta. Author(s): Valli M, Rossi A, Forlino A, Tenni R, Cetta G. Source: Matrix. 1993 July; 13(4): 275-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412984

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Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta. Author(s): Fedarko NS, Moerike M, Brenner R, Robey PG, Vetter U. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1992 August; 7(8): 921-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1442206

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Extracellular matrix stoichiometry in osteoblasts from patients with osteogenesis imperfecta. Author(s): Fedarko NS, Robey PG, Vetter UK. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1995 July; 10(7): 1122-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7484289

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Failed tissue expansion in a patient with osteogenesis imperfecta. Author(s): Stark GB, Jaeger K. Source: Annals of Plastic Surgery. 1989 February; 22(2): 156-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2735711

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Familial dentinogenesis imperfecta, blue sclerae, and wormian bones without fractures: another type of osteogenesis imperfecta? Author(s): Beighton P. Source: Journal of Medical Genetics. 1981 April; 18(2): 124-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7241530

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Familial leukemia and osteogenesis imperfecta. Author(s): Gilchrist GS, Shore NA. Source: The Journal of Pediatrics. 1967 July; 71(1): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5294018

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Familial occurrence of hyperplastic callus in osteogenesis imperfecta. Author(s): Nakamura K, Kurokawa T, Nagano A, Umeyama T. Source: Archives of Orthopaedic and Trauma Surgery. 1997; 116(8): 500-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9352048

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Familial tarda type osteogenesis imperfecta with dentinogenesis imperfecta Type I. Case report. Author(s): Ogunsalu C, Hanchard B. Source: Aust Dent J. 1997 June; 42(3): 175-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9241928

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Fatal intraoperative hemorrhage during spinal fusion surgery for osteogenesis imperfecta. Author(s): Sperry K. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1989 March; 10(1): 54-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2929544

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Findings and long-term surgical results in the hearing loss of osteogenesis imperfecta. Author(s): Shea JJ, Postma DS. Source: Arch Otolaryngol. 1982 August; 108(8): 467-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7103822

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First-trimester diagnosis of osteogenesis imperfecta associated with encephalocele by conventional and three-dimensional ultrasound. Author(s): Ruano R, Picone O, Benachi A, Grebille AG, Martinovic J, Dumez Y, Dommergues M. Source: Prenatal Diagnosis. 2003 July; 23(7): 539-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868078

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First-trimester diagnosis of osteogenesis imperfecta type II by three-dimensional sonography. Author(s): McEwing RL, Alton K, Johnson J, Scioscia AL, Pretorius DH. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2003 March; 22(3): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636334

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First-trimester prenatal diagnosis of osteogenesis imperfecta type II by DNA analysis and sonography. Author(s): DiMaio MS, Barth R, Koprivnikar KE, Sussman BL, Copel JA, Mahoney MJ, Byers PH, Cohn DH. Source: Prenatal Diagnosis. 1993 July; 13(7): 589-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8415424

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Flail chest in the newborn. A complication of osteogenesis imperfecta. Author(s): Cardenas N, Manrique TA, Catlin EA. Source: Clinical Pediatrics. 1988 March; 27(3): 161-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3342600

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Four new cases of lethal osteogenesis imperfecta due to glycine substitutions in COL1A1 and genes. Mutations in brief no. 152. Online. Author(s): Mottes M, Gomez Lira M, Zolezzi F, Valli M, Lisi V, Freising P. Source: Human Mutation. 1998; 12(1): 71-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10627137

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Fourteen cases of osteogenesis imperfecta. Author(s): Asafo-Agyei AP. Source: Annals of Tropical Paediatrics. 1988 June; 8(2): 122. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2456729

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Fracture failure mechanisms in patients with osteogenesis imperfecta. Author(s): Alman B, Frasca P. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 1987; 5(1): 139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3819906

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Fractures in early childhood: osteogenesis imperfecta or child abuse? Author(s): Dent JA, Paterson CR. Source: Journal of Pediatric Orthopedics. 1991 March-April; 11(2): 184-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2010517

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Frameshift mutation near the 3' end of the COL1A1 gene of type I collagen predicts an elongated Pro alpha 1(I) chain and results in osteogenesis imperfecta type I. Author(s): Willing MC, Cohn DH, Byers PH. Source: The Journal of Clinical Investigation. 1990 January; 85(1): 282-90. Erratum In: J Clin Invest 1990 April; 85(4): Following 1338. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2295701

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Frontal bone fractures, scalp flap, and expander in a patient with osteogenesis imperfecta. Author(s): Voukidis TE. Source: Plastic and Reconstructive Surgery. 1988 June; 81(6): 987-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3375366

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Functional outcome of Sofield procedure in the upper limb in osteogenesis imperfecta. Author(s): Khoshhal KI, Ellis RD. Source: Journal of Pediatric Orthopedics. 2001 March-April; 21(2): 236-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11242258

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Functional results of operation in osteogenesis imperfecta: elongating and nonelongating rods. Author(s): Porat S, Heller E, Seidman DS, Meyer S. Source: Journal of Pediatric Orthopedics. 1991 March-April; 11(2): 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2010521

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Further experiences with sodium fluoride treatment in osteogenesis imperfecta. Author(s): Bilginturan N, Ozsoylu S, Yordam N. Source: Turk J Pediatr. 1982 July-September; 24(3): 151-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7147363

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Gastrointestinal problems and osteogenesis imperfecta. Author(s): Hensinger RN. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 November; 78(11): 1785. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8934498

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Gastrointestinal problems in patients who have type-III osteogenesis imperfecta. Author(s): Lee JH, Gamble JG, Moore RE, Rinsky LA. Source: The Journal of Bone and Joint Surgery. American Volume. 1995 September; 77(9): 1352-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7673285

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Gene targeting in stem cells from individuals with osteogenesis imperfecta. Author(s): Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD, Pace JM, Underwood RA, Song KM, Sussman M, Byers PH, Russell DW. Source: Science. 2004 February 20; 303(5661): 1198-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976317

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General strategies for isolating the genes encoding type I collagen and for characterizing mutations which produce osteogenesis imperfecta. Author(s): Cohn DH, Wenstrup RJ, Willing MC, Bonadio JF, Byers PH. Source: Annals of the New York Academy of Sciences. 1988; 543: 129-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3063159

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Genetic counseling in osteogenesis imperfecta. Author(s): Lubs HA, Travers H. Source: Clinical Orthopaedics and Related Research. 1981 September; (159): 36-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7285468

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Genetic counselling and prenatal diagnosis of osteogenesis imperfecta caused by paternal mosaicism. Author(s): Lund AM, Schwartz M, Skovby F. Source: Prenatal Diagnosis. 1996 November; 16(11): 1032-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8953637

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Genetic counselling in perinatally lethal and severe progressively deforming osteogenesis imperfecta. Author(s): Thompson EM, Young ID, Hall CM, Pembrey ME. Source: Annals of the New York Academy of Sciences. 1988; 543: 142-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3214049

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Genetic counselling on brittle grounds: recurring osteogenesis imperfecta due to parental mosaicism for a dominant mutation. Author(s): Raghunath M, Mackay K, Dalgleish R, Steinmann B. Source: European Journal of Pediatrics. 1995 February; 154(2): 123-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7720740

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Genetic heterogeneity in osteogenesis imperfecta. Author(s): Sillence DO, Senn A, Danks DM. Source: Journal of Medical Genetics. 1979 April; 16(2): 101-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=458828

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Gly802Asp substitution in the pro alpha 2(I) collagen chain in a family with recurrent osteogenesis imperfecta due to paternal mosaicism. Author(s): Lund AM, Schwartz M, Raghunath M, Steinmann B, Skovby F. Source: European Journal of Human Genetics : Ejhg. 1996; 4(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8800927

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Gly85 to Val substitution in pro alpha 1(I) chain causes mild osteogenesis imperfecta and introduces a susceptibility to protease digestion. Author(s): Valli M, Zolezzi F, Mottes M, Antoniazzi F, Stanzial F, Tenni R, Pignatti P, Cetta G. Source: European Journal of Biochemistry / Febs. 1993 October 1; 217(1): 77-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8223589

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Glycosaminoglycan alterations in osteogenesis imperfecta. Author(s): Cetta G, Lenzi L, Balduini C, Valli M, Tenni R, De Luca G, Castellani AA. Source: Ital J Biochem. 1980 September-October; 29(5): 337-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7203991

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Glycosaminoglycan excretion in osteogenesis imperfecta. Author(s): Hurst RE, Settine JM, Floyd WM, Lorincz AE. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1980 January 31; 100(3): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7353313

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Glycosaminoglycan synthesis in skin fibroblasts from patients with osteogenesis imperfecta. Author(s): Kapoor R, Bourier S, Prehm P. Source: Febs Letters. 1983 February 21; 152(2): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6825845

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Glycosaminoglycans of cartilage and bone tissue in two cases of osteogenesis imperfecta congenita. Author(s): Engfeldt B, Hjerpe A. Source: Acta Pathol Microbiol Scand [a]. 1976 November; 84(6): 488-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=998248

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Growth hormone therapy may increase fracture risk in a pubertal patient with osteogenesis imperfecta. Author(s): Noda H, Onishi H, Saitoh K, Nakajima H. Source: J Pediatr Endocrinol Metab. 2002 February; 15(2): 217-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874188

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Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis. Author(s): Antoniazzi F, Bertoldo F, Mottes M, Valli M, Sirpresi S, Zamboni G, Valentini R, Tato L. Source: The Journal of Pediatrics. 1996 September; 129(3): 432-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8804334

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Hammerhead ribozymes selectively suppress mutant type I collagen mRNA in osteogenesis imperfecta fibroblasts. Author(s): Dawson PA, Marini JC. Source: Nucleic Acids Research. 2000 October 15; 28(20): 4013-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11024182

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Hearing loss (in nonoperated ears) in relation to age in osteogenesis imperfecta type I. Author(s): Garretsen AJ, Cremers CW, Huygen PL. Source: The Annals of Otology, Rhinology, and Laryngology. 1997 July; 106(7 Pt 1): 57582. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9228859

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Hearing loss in children with osteogenesis imperfecta. Author(s): Kuurila K, Grenman R, Johansson R, Kaitila I. Source: European Journal of Pediatrics. 2000 July; 159(7): 515-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923226

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Hearing loss in Finnish adults with osteogenesis imperfecta: a nationwide survey. Author(s): Kuurila K, Kaitila I, Johansson R, Grenman R. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 October; 111(10): 93946. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12389865

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Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV. Author(s): Zeitlin L, Rauch F, Plotkin H, Glorieux FH. Source: Pediatrics. 2003 May; 111(5 Pt 1): 1030-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728084

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Hip and knee replacement in osteogenesis imperfecta. Author(s): Papagelopoulos PJ, Morrey BF. Source: The Journal of Bone and Joint Surgery. American Volume. 1993 April; 75(4): 57280. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8478384

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Histopathologic and electron-microscopic features of corneal and scleral collagen fibers in osteogenesis imperfecta type III. Author(s): Mietz H, Kasner L, Green WR. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1997 July; 235(7): 405-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9248835

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Homozygosity by descent for a COL1A2 mutation in two sibs with severe osteogenesis imperfecta and mild clinical expression in the heterozygotes. Author(s): De Paepe A, Nuytinck L, Raes M, Fryns JP. Source: Human Genetics. 1997 April; 99(4): 478-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9099837

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How common is hearing impairment in osteogenesis imperfecta? Author(s): Paterson CR, Monk EA, McAllion SJ. Source: The Journal of Laryngology and Otology. 2001 April; 115(4): 280-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11276328

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Hydroxylation of collagen type I: evidence that both lysyl and prolyl residues are overhydroxylated in osteogenesis imperfecta. Author(s): Lehmann HW, Rimek D, Bodo M, Brenner RE, Vetter U, Worsdorfer O, Karbowski A, Muller PK. Source: European Journal of Clinical Investigation. 1995 May; 25(5): 306-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7628516

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Hypercalcaemia in osteogenesis imperfecta treated with pamidronate. Author(s): Williams CJ, Smith RA, Ball RJ, Wilkinson H. Source: Archives of Disease in Childhood. 1997 February; 76(2): 169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9068314

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Hypercalciuria in osteogenesis imperfecta type I. Author(s): Ammenti A, Nitsch M. Source: Klinische Padiatrie. 2003 September-October; 215(5): 283-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520592

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Hypercalciuria in osteogenesis imperfecta: a follow-up study to assess renal effects. Author(s): Chines A, Boniface A, McAlister W, Whyte M. Source: Bone. 1995 March; 16(3): 333-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7786636

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Hyperfibers and vesicles in dentin matrix in dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI). Author(s): Waltimo J. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1994 October; 23(9): 389-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7823299

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Hyperplastic callus and osteogenesis imperfecta. Author(s): Smith R. Source: Lancet. 2001 January 27; 357(9252): 248-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11214123

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Hyperplastic callus formation in both femurs in osteogenesis imperfecta. Author(s): Kutsumi K, Nojima T, Yamashiro K, Hatae Y, Isu K, Ubayama Y, Yamawaki S. Source: Skeletal Radiology. 1996 May; 25(4): 384-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8738006

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Hyperplastic callus formation in osteogenesis imperfecta. Author(s): Lamovec J, Mozina E, Baebler B. Source: Annals of Diagnostic Pathology. 2003 August; 7(4): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913845

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Hyperplastic callus formation in osteogenesis imperfecta. A case report. Author(s): Burchardt AJ, Wagner AA, Basse P. Source: Acta Radiologica (Stockholm, Sweden : 1987). 1994 September; 35(5): 426-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8086246

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Hyperplastic callus formation in osteogenesis imperfecta: CT and MRI findings. Author(s): Rieker O, Kreitner KF, Karbowski A. Source: European Radiology. 1998; 8(7): 1137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9724425

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Hyperplastic callus in osteogenesis imperfecta. Author(s): Xu D, Zhan A, Feng W, Liu J, Zhang C, Bi W. Source: Chinese Medical Journal. 1999 August; 112(8): 764-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11601292

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Images in clinical medicine. Blue sclerae in osteogenesis imperfecta. Author(s): Leidig-Bruckner G, Grauer A. Source: The New England Journal of Medicine. 1998 October 1; 339(14): 966. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753712

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Immunohistochemical localization of interstitial collagens in bone tissue from patients with various forms of osteogenesis imperfecta. Author(s): Nerlich AG, Brenner RE, Wiest I, Lehmann H, Yang C, Muller PK, von der Mark K. Source: American Journal of Medical Genetics. 1993 January 15; 45(2): 258-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456813

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Immunoreactivity of tenascin-C in dentin matrix in dentinogenesis imperfecta associated with osteogenesis imperfecta. Author(s): Lukinmaa PL, Allemanni G, Waltimo J, Zardi L. Source: Journal of Dental Research. 1996 January; 75(1): 581-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8655763

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Improvement of bone in patients with osteogenesis imperfecta treated with pamidronate-lessons from biochemistry. Author(s): Langman CB. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 984-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629072

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In utero clue to congenital lethal osteogenesis imperfecta. Author(s): Andrews M, Amparo EG. Source: Ajr. American Journal of Roentgenology. 1993 January; 160(1): 212. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8416637

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Incorporation of type I collagen molecules that contain a mutant alpha 2(I) chain (Gly580-->Asp) into bone matrix in a lethal case of osteogenesis imperfecta. Author(s): Niyibizi C, Bonadio J, Byers PH, Eyre DR. Source: The Journal of Biological Chemistry. 1992 November 15; 267(32): 23108-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1385413

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Increased bone resorption with decreased activity and increased recruitment of osteoblasts in osteogenesis imperfecta type I. Author(s): Iwamoto J, Takeda T, Ichimura S. Source: Journal of Bone and Mineral Metabolism. 2002; 20(3): 174-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11984701

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Increased cell surface expression of receptors for transforming growth factor-beta on osteoblasts from patients with Osteogenesis imperfecta. Author(s): Gebken J, Brenner R, Feydt A, Notbohm H, Brinckmann J, Muller PK, Batge B. Source: Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology. 2000 May-June; 68(3): 106-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11174067

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Increased nuchal translucency in the first trimester as a sign of osteogenesis imperfecta. Author(s): Viora E, Sciarrone A, Bastonero S, Errante G, Campogrande M, Botta G, Franceschini P. Source: American Journal of Medical Genetics. 2002 May 15; 109(4): 336-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992492

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Increased postoperative febrile response in children with osteogenesis imperfecta. Author(s): Ghert M, Allen B, Davids J, Stasikelis P, Nicholas D. Source: Journal of Pediatric Orthopedics. 2003 March-April; 23(2): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604962

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Index of suspicion. Case 2. Osteogenesis imperfecta. Author(s): Sehgal N. Source: Pediatrics in Review / American Academy of Pediatrics. 1993 June; 14(6): 215-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8327396

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Initial experience using magnetic resonance imaging in prenatal diagnosis of osteogenesis imperfecta type II: a case report. Author(s): Teng SW, Guo WY, Sheu MH, Wang PH. Source: Clinical Imaging. 2003 January-February; 27(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504324

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Intramedullary rodding in osteogenesis imperfecta. Author(s): Mulpuri K, Joseph B. Source: Journal of Pediatric Orthopedics. 2000 March-April; 20(2): 267-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10739296

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Intramedullary rodding in type III osteogenesis imperfecta. Effects on neuromotor development in 10 children. Author(s): Engelbert RH, Helders PJ, Keessen W, Pruijs HE, Gooskens RH. Source: Acta Orthopaedica Scandinavica. 1995 August; 66(4): 361-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7676827

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Intravenous bisphosphonate therapy in children with osteogenesis imperfecta. Author(s): Falk MJ, Heeger S, Lynch KA, DeCaro KR, Bohach D, Gibson KS, Warman ML. Source: Pediatrics. 2003 March; 111(3): 573-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612238

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Intravenous neridronate in adults with osteogenesis imperfecta. Author(s): Adami S, Gatti D, Colapietro F, Fracassi E, Braga V, Rossini M, Tato L. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 January; 18(1): 126-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12510813

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Intravenous pamidronate treatment in osteogenesis imperfecta. Author(s): Fujiwara I, Ogawa E, Igarashi Y, Ohba M, Asanuma A. Source: European Journal of Pediatrics. 1998 March; 157(3): 261-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9537501

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Intravenous pamidronate treatment in osteogenesis imperfecta. Author(s): Bembi B, Parma A, Bottega M, Ceschel S, Zanatta M, Martini C, Ciana G. Source: The Journal of Pediatrics. 1997 October; 131(4): 622-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9386671

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Is it necessary to screen for hearing loss in the paediatric population with osteogenesis imperfecta? Author(s): Imani P, Vijayasekaran S, Lannigan F. Source: Clinical Otolaryngology and Allied Sciences. 2003 June; 28(3): 199-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755755

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Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Author(s): Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 June 25; 99(13): 8932-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084934

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Just taller or more bone? The impact of growth hormone on osteogenesis imperfecta and idiopathic juvenile osteoporosis. Author(s): Wright NM. Source: J Pediatr Endocrinol Metab. 2000 September; 13 Suppl 2: 999-1002. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11086654

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Lack of effects of human calcitonin in osteogenesis imperfecta. Author(s): Pedersen U, Charles P, Hansen HH, Elbrond O. Source: Acta Orthopaedica Scandinavica. 1985 June; 56(3): 260-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4036580

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Large cementifying fibroma in a patient with osteogenesis imperfecta. Author(s): Shibahara T, Noma H, Yamane GY, Hashimoto S. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1996 August; 54(8): 1016-9; Discussion 1019-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8765392

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Laryngomalacia causing sleep apnea in an osteogenesis imperfecta patient. Author(s): Li HY, Fang TJ, Lin JL, Lee ZL, Lee LA. Source: American Journal of Otolaryngology. 2002 November-December; 23(6): 378-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12430132

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Left atrial rupture in osteogenesis imperfecta. Author(s): Rogerson ME, Buchanan JD, Morgans CM. Source: British Heart Journal. 1986 August; 56(2): 187-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3730222

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Left ventricular rupture after mitral valve replacement in a patient with osteogenesis imperfecta tarda. Author(s): Lijoi A, Cisico S, Caputo E, Scarano F, Parodi E, Passerone GC. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 1999; 26(4): 295-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10653260

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Lethal osteogenesis imperfecta and a collagen gene deletion. Length polymorphism provides an alternative explanation. Author(s): Sykes BC, Ogilvie DJ, Wordsworth BP. Source: Human Genetics. 1985; 70(1): 35-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3997150

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Lethal osteogenesis imperfecta and a gene deletion. Author(s): Sykes B, Ogilvie D. Source: British Medical Journal (Clinical Research Ed.). 1984 May 5; 288(6427): 1380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6424862

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Lethal osteogenesis imperfecta associated with 46,XY,inv(7)(p13q22) karyotype. Author(s): Knisely AS, Richardson A, Abuelo D, Casey S, Singer DB. Source: Journal of Medical Genetics. 1988 May; 25(5): 352-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3385745

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Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro alpha 1(I) collagen allele. Author(s): Cohn DH, Byers PH, Steinmann B, Gelinas RE. Source: Proceedings of the National Academy of Sciences of the United States of America. 1986 August; 83(16): 6045-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3016737

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Lethal osteogenesis imperfecta with amniotic band lesions: collagen studies. Author(s): van der Rest M, Hayes A, Marie P, Desbarats M, Kaplan P, Glorieux FH. Source: American Journal of Medical Genetics. 1986 July; 24(3): 433-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3728562

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Lethal osteogenesis imperfecta. Author(s): Knisely AS, Abuelo D, Byers PH. Source: Journal of Medical Genetics. 1989 June; 26(6): 410-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2738906

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Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia. Author(s): Royce PM, Blumberg A, Zurbrugg RP, Zimmermann A, Colombo JP, Steinmann B. Source: European Journal of Pediatrics. 1988 August; 147(6): 626-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3181205

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Lethal osteogenesis imperfecta: second trimester sonographic diagnosis in a twin gestation. Author(s): Wax JR, Smith JF, Floyd RC. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1994 September; 13(9): 711-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7933048

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Lethal perinatal osteogenesis imperfecta due to a type I collagen alpha 2(I) Gly to Arg substitution detected by chemical cleavage of an mRNA:cDNA sequence mismatch. Author(s): Bateman JF, Moeller I, Hannagan M, Chan D, Cole WG. Source: Human Mutation. 1992; 1(1): 55-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1284475

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Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the alpha 1(I) chain of type I collagen. Author(s): Bateman JF, Chan D, Walker ID, Rogers JG, Cole WG. Source: The Journal of Biological Chemistry. 1987 May 25; 262(15): 7021-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3108247

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Life expectancy in osteogenesis imperfecta. Author(s): Paterson CR, Ogston SA, Henry RM. Source: Bmj (Clinical Research Ed.). 1996 February 10; 312(7027): 351. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8611834

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Linkage analysis in dominantly inherited osteogenesis imperfecta. Author(s): Sykes B. Source: American Journal of Medical Genetics. 1993 January 15; 45(2): 212-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456805

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Localization of a structural defect in type I procollagen in a patient affected with the severe non-lethal form of Osteogenesis imperfecta. Author(s): Dyne K, Cetta G, Tenni R, Rossi A, Finardi E, Brunelli PC, Castellani AA. Source: Ital J Biochem. 1987 July-August; 36(4): 256-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3429209

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Long-term extracellular matrix metabolism by cultured human osteogenesis imperfecta osteoblasts. Author(s): Fedarko NS, Sponseller PD, Shapiro JR. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1996 June; 11(6): 800-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8725177

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Lysyl oxidase in osteogenesis imperfecta and Marfan's syndrome. Author(s): Royce PM, Steinmann B. Source: Coll Relat Res. 1988 March; 8(2): 183-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2897892

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Management of lower-extremity deformities in osteogenesis imperfecta with extensible intramedullary rod technique: a 20-year experience. Author(s): Luhmann SJ, Sheridan JJ, Capelli AM, Schoenecker PL. Source: Journal of Pediatric Orthopedics. 1998 January-February; 18(1): 88-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9449108

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Management of pregnancy complicated by maternal osteogenesis imperfecta. Report of a case with uterine rupture. Author(s): Krishnamoorthy U, Vausse S, Donnai P. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 May; 22(3): 316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521511

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Management of retinal detachment in osteogenesis imperfecta. Author(s): Eliott D, Rezai KA, Dass AB, Lewis J. Source: Archives of Ophthalmology. 2003 July; 121(7): 1062-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860823

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Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Author(s): Pereira RF, O'Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 February 3; 95(3): 1142-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9448299

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Mild forms of dentinogenesis imperfecta in association with osteogenesis imperfecta as characterized by light and transmission electron microscopy. Author(s): Waltimo J, Ojanotko-Harri A, Lukinmaa PL. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1996 May; 25(5): 256-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835824

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Mild hypophosphatasia mimicking severe osteogenesis imperfecta in utero: bent but not broken. Author(s): Pauli RM, Modaff P, Sipes SL, Whyte MP. Source: American Journal of Medical Genetics. 1999 October 29; 86(5): 434-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10508985

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Ministernotomy for aortic valve replacement in a patient with osteogenesis imperfecta. Author(s): Izzat MB, Wan S, Wan IY, Khaw KS, Yim AP. Source: The Annals of Thoracic Surgery. 1999 April; 67(4): 1171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10320279

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Modeling the benefits of pamidronate in children with osteogenesis imperfecta. Author(s): Lindsay R. Source: The Journal of Clinical Investigation. 2002 November; 110(9): 1239-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417561

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Modern approach to children with osteogenesis imperfecta. Author(s): Zeitlin L, Fassier F, Glorieux FH. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2003 March; 12(2): 77-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584489

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Morphology of dental enamel and dentine-enamel junction in osteogenesis imperfecta. Author(s): Lindau BM, Dietz W, Hoyer I, Lundgren T, Storhaug K, Noren JG. Source: International Journal of Paediatric Dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children. 1999 March; 9(1): 13-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10336712

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Morphometric analysis of type I collagen fibrils in the osteoid of osteogenesis imperfecta. Author(s): Sarathchandra P, Pope FM, Ali SY. Source: Calcified Tissue International. 1999 November; 65(5): 390-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541766

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Mortality in various types of osteogenesis imperfecta. Author(s): Singer RB, Ogston SA, Paterson CR. Source: J Insur Med. 2001; 33(3): 216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11558400

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MRI and CT features of hyperplastic callus in osteogenesis imperfecta tarda. Author(s): Dobrocky I, Seidl G, Grill F. Source: European Radiology. 1999; 9(4): 665-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10354881

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MRI-visible pericochlear lesions in osteogenesis imperfecta type I. Author(s): Ziyeh S, Berger R, Reisner K. Source: European Radiology. 2000; 10(10): 1675-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044947

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Musculoskeletal images. Femoral fracture in adult osteogenesis imperfecta. Author(s): Theodoropoulos JS, Reindl R, Berry G, Harvey EJ. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2003 August; 46(4): 297-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930108

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Musculo-skeletal problems associated with pregnancy in women with osteogenesis imperfecta. Author(s): McAllion SJ, Paterson CR. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 March; 22(2): 169-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521699

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Mutation in the carboxy-terminal propeptide of the Pro alpha 1(I) chain of type I collagen in a child with severe osteogenesis imperfecta (OI type III): possible implications for protein folding. Author(s): Oliver JE, Thompson EM, Pope FM, Nicholls AC. Source: Human Mutation. 1996; 7(4): 318-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723681

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Mutation producing alternative splicing of exon 26 in the COL1A2 gene causes type IV osteogenesis imperfecta with intrafamilial clinical variability. Author(s): Zolezzi F, Valli M, Clementi M, Mammi I, Cetta G, Pignatti PF, Mottes M. Source: American Journal of Medical Genetics. 1997 August 22; 71(3): 366-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9268111

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Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans. Author(s): Gajko-Galicka A. Source: Acta Biochimica Polonica. 2002; 49(2): 433-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362985

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Natural history of blue sclerae in osteogenesis imperfecta. Author(s): Sillence D, Butler B, Latham M, Barlow K. Source: American Journal of Medical Genetics. 1993 January 15; 45(2): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456800

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New insights into the molecular pathology of osteogenesis imperfecta. Author(s): Cole WG, Jaenisch R, Bateman JF. Source: The Quarterly Journal of Medicine. 1989 January; 70(261): 1-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2687927

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New uses of bisphosphonates: osteogenesis imperfecta. Author(s): Devogelaer JP. Source: Current Opinion in Pharmacology. 2002 December; 2(6): 748-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482741

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Nonaccidental injury in osteogenesis imperfecta: a case report. Author(s): Knight DJ, Bennet GC. Source: Journal of Pediatric Orthopedics. 1990 July-August; 10(4): 542-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2358497

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Non-accidental injury: confusion with temporary brittle bone disease and mild osteogenesis imperfecta. Author(s): Ablin DS, Sane SM. Source: Pediatric Radiology. 1997 February; 27(2): 111-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9028840

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Non-invasive prenatal diagnosis of osteogenesis imperfecta. Author(s): Thompson EM. Source: American Journal of Medical Genetics. 1993 January 15; 45(2): 201-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456803

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Nonsense mutations in the COL1A1 gene preferentially reduce nuclear levels of mRNA but not hnRNA in osteogenesis imperfecta type I cell strains. Author(s): Slayton RL, Deschenes SP, Willing MC. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 2000 February; 19(1): 1-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10686420

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Non-union of fractures in children who have osteogenesis imperfecta. Author(s): Gamble JG, Rinsky LA, Strudwick J, Bleck EE. Source: The Journal of Bone and Joint Surgery. American Volume. 1988 March; 70(3): 439-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3346270

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Normal thermal stability of an overmodified type I collagen despite a structural mutation within the triple helical region in a case of osteogenesis imperfecta type IVB. Author(s): Royce PM, Superti-Furga A, Rao VH, Steinmann B. Source: Annals of the New York Academy of Sciences. 1988; 543: 83-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3214055

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Nuclear retention of COL1A1 messenger RNA identifies null alleles causing mild osteogenesis imperfecta. Author(s): Redford-Badwal DA, Stover ML, Valli M, McKinstry MB, Rowe DW. Source: The Journal of Clinical Investigation. 1996 February 15; 97(4): 1035-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8613526

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Orthodontic and orthognathic management of a patient with osteogenesis imperfecta and dentinogenesis imperfecta: a case report. Author(s): Kindelan J, Tobin M, Roberts-Harry D, Loukota RA. Source: Journal of Orthodontics. 2003 December; 30(4): 291-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14634166

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Osteogenesis imperfecta calls for caution. Author(s): Bishop NJ. Source: Nature Medicine. 1999 May; 5(5): 466-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10229208

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Osteogenesis imperfecta calls for caution. Author(s): Marini JC. Source: Nature Medicine. 1999 May; 5(5): 466-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10229207

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Osteogenesis imperfecta in childhood: treatment strategies. Author(s): Engelbert RH, Pruijs HE, Beemer FA, Helders PJ. Source: Archives of Physical Medicine and Rehabilitation. 1998 December; 79(12): 15904. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862306

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Osteogenesis imperfecta in Zimbabwe: a comparison between treatment with intramedullary rods of fixed-length and self-expanding rods. Author(s): Harrison WJ, Rankin KC. Source: Journal of the Royal College of Surgeons of Edinburgh. 1998 October; 43(5): 32832. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9803105

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Osteogenesis imperfecta: mosaicism and refinement of the genotype-phenotype map in OI type III. Mutations in brief no. 242. Online. Author(s): Lund AM, Astrom E, Soderhall S, Schwartz M, Skovby F. Source: Human Mutation. 1999; 13(6): 503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408781

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Osteogenesis imperfecta--clinical and molecular diversity. Author(s): Roughley PJ, Rauch F, Glorieux FH. Source: European Cells & Materials [electronic Resource]. 2003 June 30; 5: 41-7; Discussion 47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562271

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Osteogenesis imperfecta-like syndrome with severe mental retardation and extrapyramidal tract signs. Author(s): Nishimura G, Kurosawa K, Kobayashi H, Kawame H. Source: Pediatric Radiology. 1998 November; 28(11): 856-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9799318

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Osteogenesis imperfecta--managing brittle bones. Author(s): Marini JC. Source: The New England Journal of Medicine. 1998 October 1; 339(14): 986-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753715

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Osteosarcoma of the scapula arising in osteogenesis imperfecta. Author(s): Bedi HS, Kaufman DV, Choong PF, Slavin JL. Source: Pathology. 1999 February; 31(1): 52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10212924

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Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response. Author(s): Zacharin M, Bateman J. Source: J Pediatr Endocrinol Metab. 2002 February; 15(2): 163-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874181

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Pamidronate treatment of severe osteogenesis imperfecta in a newborn infant. Author(s): Chien YH, Chu SY, Hsu CC, Hwu WL. Source: Journal of Inherited Metabolic Disease. 2002 November; 25(7): 593-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12638943

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Percutaneous vertebroplasty in the treatment of vertebral body compression fracture secondary to osteogenesis imperfecta. Author(s): Rami PM, McGraw JK, Heatwole EV, Boorstein JM. Source: Skeletal Radiology. 2002 March; 31(3): 162-5. Epub 2001 December 18. Erratum In: Skeletal Radiol 2002 September; 31(9): 558. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11935201

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Perthes' disease associated with osteogenesis imperfecta. Author(s): Petra M, Benson MK. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2003 September; 12(5): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973039

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Pictorial CME. Osteogenesis imperfecta. Author(s): Sahay RK, Unnikrishnan AG, Bhadada SK, Reddy V, Singh SK, Agrawal JK. Source: J Assoc Physicians India. 2001 April; 49: 450. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762617

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Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen. Author(s): Marini JC, Hopkins E, Glorieux FH, Chrousos GP, Reynolds JC, Gundberg CM, Reing CM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12568401

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Potential of gene therapy for treating osteogenesis imperfecta. Author(s): Niyibizi C, Smith P, Mi Z, Robbins P, Evans C. Source: Clinical Orthopaedics and Related Research. 2000 October; (379 Suppl): S126-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11039761

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Pregnancy complicated by severe osteogenesis imperfecta: a report of two cases. Author(s): Vogel TM, Ratner EF, Thomas RC Jr, Chitkara U. Source: Anesthesia and Analgesia. 2002 May; 94(5): 1315-7, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973211

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Prenatal diagnosis of a novel COL1A1 mutation in osteogenesis imperfecta type I carried through full term pregnancy. Author(s): Ries L, Frydman M, Barkai G, Goldman B, Friedman E. Source: Prenatal Diagnosis. 2000 November; 20(11): 876-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11113887

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Pseudomass of the sternal manubrium in osteogenesis imperfecta. Author(s): Yekeler E, Kumbasar B, Dursun M, Cantez S, Emiroglu HH, Tunaci M. Source: Skeletal Radiology. 2003 June; 32(6): 371-3. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728341

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Quality of life in osteogenesis imperfecta. Author(s): Widmann RF, Laplaza FJ, Bitan FD, Brooks CE, Root L. Source: International Orthopaedics. 2002; 26(1): 3-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11954845

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Quiz case 7. Osteogenesis imperfecta tarda with association of the inner ear also called Van Hoeve-Klein-syndrome. Author(s): Czerny C, Temmel AF. Source: European Journal of Radiology. 1999 May; 30(2): 162-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401597

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Rapid increase in grip force after start of pamidronate therapy in children and adolescents with severe osteogenesis imperfecta. Author(s): Montpetit K, Plotkin H, Rauch F, Bilodeau N, Cloutier S, Rabzel M, Glorieux FH. Source: Pediatrics. 2003 May; 111(5 Pt 1): E601-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728117

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Re: Prince SE, Simpson MT. Osteogenesis imperfecta. Br J Oral Maxillofac Surg 2000; 38: 399-400. Author(s): Ribeiro NF, El Rasheed A, Cousin GC. Source: The British Journal of Oral & Maxillofacial Surgery. 2001 October; 39(5): 407. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11724025

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Recent findings in classification of osteogenesis imperfecta by means of existing dental symptoms. Author(s): Petersen K, Wetzel WE. Source: Asdc J Dent Child. 1998 September-October; 65(5): 305-9, 354. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9795732

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Recombinant factor VIIa after aortic valve replacement in a patient with osteogenesis imperfecta. Author(s): Kastrup M, von Heymann C, Hotz H, Konertz WF, Ziemer S, Kox WJ, Spies C. Source: The Annals of Thoracic Surgery. 2002 September; 74(3): 910-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12238862

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Recurrent mutations in the COL1A2 gene in patients with osteogenesis imperfecta. Author(s): Trummer T, Brenner R, Just W, Vogel W, Kennerknecht I. Source: Clinical Genetics. 2001 May; 59(5): 338-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359465

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Redefinition of exon 7 in the COL1A1 gene of type I collagen by an intron 8 splicedonor-site mutation in a form of osteogenesis imperfecta: influence of intron splice order on outcome of splice-site mutation. Author(s): Schwarze U, Starman BJ, Byers PH. Source: American Journal of Human Genetics. 1999 August; 65(2): 336-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417276

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Renal stone disease as extra skeletal manifestation of osteogenesis imperfecta. Author(s): Venugopala D, Babu S, Korath MP, Jagadeesan K. Source: J Assoc Physicians India. 2000 October; 48(10): 1027-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11200907

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Results of stapes surgery on patients with osteogenesis imperfecta. Author(s): Albahnasawy L, Kishore A, O'Reilly BF. Source: Clinical Otolaryngology and Allied Sciences. 2001 December; 26(6): 473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843926

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Retrovirally transduced bone marrow stromal cells isolated from a mouse model of human osteogenesis imperfecta (oim) persist in bone and retain the ability to form cartilage and bone after extended passaging. Author(s): Oyama M, Tatlock A, Fukuta S, Kavalkovich K, Nishimura K, Johnstone B, Robbins PD, Evans CH, Niyibizi C. Source: Gene Therapy. 1999 March; 6(3): 321-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435082

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Rod diameter prediction in patients with osteogenesis imperfecta undergoing primary osteotomy. Author(s): Chotigavanichaya C, Jadhav A, Bernstein RM, Watts HG. Source: Journal of Pediatric Orthopedics. 2001 July-August; 21(4): 515-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11433167

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Scoliosis in children with osteogenesis imperfecta: influence of severity of disease and age of reaching motor milestones. Author(s): Engelbert RH, Uiterwaal CS, van der Hulst A, Witjes B, Helders PJ, Pruijs HE. Source: European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2003 April; 12(2): 130-4. Epub 2002 December 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709850

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Significance of histopathologic examination in the diagnosis of dentin defects associated with type IV osteogenesis imperfecta: two case reports. Author(s): Koreeda-Miura M, Onishi T, Ooshima T. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 January; 95(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12539032

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Similar COL1A1 expression in fibroblasts from some patients with clinical otosclerosis and those with type I osteogenesis imperfecta. Author(s): McKenna MJ, Kristiansen AG, Tropitzsch AS. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 February; 111(2): 1849. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11860074

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Sleeve fracture of the upper pole of the patella in an adult with osteogenesis imperfecta. Author(s): Kakazu T, Tatemoto H, Kawamura M, Sugita T. Source: Injury. 2003 October; 34(10): 793-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519364

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Spinal anesthesia in an obese patient with osteogenesis imperfecta. Author(s): Aly EE, Harris P. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 April; 50(4): 421-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670824

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Spondylolisthesis in osteogenesis imperfecta due to pedicle elongation: report of two cases. Author(s): Basu PS, Hilali Noordeen MH, Elsebaie H. Source: Spine. 2001 November 1; 26(21): E506-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11679836

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Stapes surgery in osteogenesis imperfecta: results of a new series. Author(s): van der Rijt AJ, Cremers CW. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 September; 24(5): 717-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501445

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Strategy for prenatal diagnosis of osteogenesis imperfecta by linkage analysis to the type I collagen loci COL1A1 and COL1A2. Author(s): Benuslene E, Kucinskas V. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 March-April; 6(2): 217-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208313

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Structural models of osteogenesis imperfecta-associated variants in the COL1A1 gene. Author(s): Mooney SD, Klein TE. Source: Molecular & Cellular Proteomics : Mcp. 2002 November; 1(11): 868-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488462

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Surgical stabilisation of the lower limb in osteogenesis imperfecta using the Sheffield Telescopic Intramedullary Rod System. Author(s): Wilkinson JM, Scott BW, Clarke AM, Bell MJ. Source: The Journal of Bone and Joint Surgery. British Volume. 1998 November; 80(6): 999-1004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853492

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Temperament and physical performance in children with osteogenesis imperfecta. Author(s): Suskauer SJ, Cintas HL, Marini JC, Gerber LH. Source: Pediatrics. 2003 February; 111(2): E153-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12563089

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The microscopic structure of bone in normal children and patients with osteogenesis imperfecta: a survey using backscattered electron imaging. Author(s): Jones SJ, Glorieux FH, Travers R, Boyde A. Source: Calcified Tissue International. 1999 January; 64(1): 8-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9868277

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The mineralization density of iliac crest bone from children with osteogenesis imperfecta. Author(s): Boyde A, Travers R, Glorieux FH, Jones SJ. Source: Calcified Tissue International. 1999 March; 64(3): 185-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10024373

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The role of dual energy x-ray absorptiometry in aiding the diagnosis of pediatric osteogenesis imperfecta. Author(s): Moore MS, Minch CM, Kruse RW, Harcke HT, Jacobson L, Taylor A. Source: Am J Orthop. 1998 December; 27(12): 797-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9880097

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The volumetric bone density and cortical thickness in adult patients affected by osteogenesis imperfecta. Author(s): Gatti D, Colapietro F, Fracassi E, Sartori E, Antoniazzi F, Braga V, Rossini M, Adami S. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2003 Summer; 6(2): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794240

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Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Author(s): Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK. Source: Nature Medicine. 1999 March; 5(3): 309-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10086387

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Treatment of children with Osteogenesis imperfecta in Estonia. Author(s): Maasalu K, Haviko T, Martson A. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 April; 92(4): 452-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801112

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Type I and type III procollagen propeptides in amniotic fluid of normal pregnancies and in a case of mild osteogenesis imperfecta. Author(s): Kauppila S, Tekay A, Risteli L, Koivisto M, Risteli J. Source: European Journal of Clinical Investigation. 1998 October; 28(10): 831-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9792997

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Type I collagen triplet duplication mutation in lethal osteogenesis imperfecta shifts register of alpha chains throughout the helix and disrupts incorporation of mutant helices into fibrils and extracellular matrix. Author(s): Cabral WA, Mertts MV, Makareeva E, Colige A, Tekin M, Pandya A, Leikin S, Marini JC. Source: The Journal of Biological Chemistry. 2003 March 21; 278(12): 10006-12. Epub 2003 January 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538651

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Type I osteogenesis imperfecta: diagnostic difficulties. Author(s): Bischoff H, Freitag P, Jundt G, Steinmann B, Tyndall A, Theiler R. Source: Clinical Rheumatology. 1999; 18(1): 48-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10088950

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Ulnar artery aneurysm in osteogenesis imperfecta. Author(s): Moore JB, Zook EG, Kinkead LR. Source: Hand. 1983 February; 15(1): 91-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6852666

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Ultrastructural localization of proteoglycans in bone in osteogenesis imperfecta as demonstrated by Cuprolinic Blue staining. Author(s): Sarathchandra P, Cassella JP, Ali SY. Source: Journal of Bone and Mineral Metabolism. 2002; 20(5): 288-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12203034

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Ultrastructural studies of bones from patients with osteogenesis imperfecta. Author(s): Traub W, Arad T, Vetter U, Weiner S. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 1994 August; 14(4): 337-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7827757

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Ultrastructural study on the stapes and skin in a case of type I Osteogenesis Imperfecta. Author(s): Vitellaro-Zuccarello L, Garino Canina G, De Biasi S, Cocchini F, VitellaroZuccarello P. Source: J Submicrosc Cytol. 1984 October; 16(4): 779-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6542149

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Unusual bone scan of a child with osteogenesis imperfecta. Author(s): Yurekli Y, Erdogan S, Cullu E. Source: Clinical Nuclear Medicine. 2003 February; 28(2): 156. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544144

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Unusual dentinal changes in dentinogenesis imperfecta associated with osteogenesis imperfecta. A case report. Author(s): Aldred MJ. Source: Oral Surg Oral Med Oral Pathol. 1992 April; 73(4): 461-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1574308

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Upper cervical cord compression as cause of death in osteogenesis imperfecta type II. Author(s): Pauli RM, Gilbert EF. Source: The Journal of Pediatrics. 1986 April; 108(4): 579-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3958833

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Urinary-free amino acids in osteogenesis imperfecta. Author(s): Cole WG, Kirby DM. Source: Bone. 1986; 7(1): 13-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3964493

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Use of molecular haplotypes specific for the human pro alpha 2(I) collagen gene in linkage analysis of the mild autosomal dominant forms of osteogenesis imperfecta. Author(s): Falk CT, Schwartz RC, Ramirez F, Tsipouras P. Source: American Journal of Human Genetics. 1986 March; 38(3): 269-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3006479

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Use of the Cre/lox recombination system to develop a non-lethal knock-in murine model for osteogenesis imperfecta with an alpha1(I) G349C substitution. Variability in phenotype in BrtlIV mice. Author(s): Forlino A, Porter FD, Lee EJ, Westphal H, Marini JC. Source: The Journal of Biological Chemistry. 1999 December 31; 274(53): 37923-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10608859

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Validation in mesenchymal progenitor cells of a mutation-independent ex vivo approach to gene therapy for osteogenesis imperfecta. Author(s): Millington-Ward S, Allers C, Tuohy G, Conget P, Allen D, McMahon HP, Kenna PF, Humphries P, Farrar GJ. Source: Human Molecular Genetics. 2002 September 15; 11(19): 2201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217948

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Valvular heart disease in osteogenesis imperfecta. Author(s): Stein D, Kloster FE. Source: American Heart Journal. 1977 November; 94(5): 637-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=143883

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Variable expression of osteogenesis imperfecta in a nuclear family is explained by somatic mosaicism for a lethal point mutation in the alpha 1(I) gene (COL1A1) of type I collagen in a parent. Author(s): Wallis GA, Starman BJ, Zinn AB, Byers PH. Source: American Journal of Human Genetics. 1990 June; 46(6): 1034-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2339700

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Variable prenatal appearance of osteogenesis imperfecta. Author(s): Bulas DI, Stern HJ, Rosenbaum KN, Fonda JA, Glass RB, Tifft C. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1994 June; 13(6): 419-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8083940

•

Variations in the serum concentration and urine excretion of alpha 2HS-glycoprotein, a bone-related protein, in normal individuals and in patients with osteogenesis imperfecta. Author(s): Dickson IR, Bagga M, Paterson CR. Source: Calcified Tissue International. 1983; 35(1): 16-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6839187

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Vertebral body shape as a predictor of spinal deformity in osteogenesis imperfecta. Author(s): Ishikawa S, Kumar SJ, Takahashi HE, Homma M. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 February; 78(2): 212-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8609111

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Vertebral bone mineral content in osteogenesis imperfecta. Author(s): Kurtz D, Morrish K, Shapiro J. Source: Calcified Tissue International. 1985 January; 37(1): 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3922591

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Vestibular dysfunction in adult patients with osteogenesis imperfecta. Author(s): Kuurila K, Kentala E, Karjalainen S, Pynnonen S, Kovero O, Kaitila I, Grenman R, Waltimo J. Source: American Journal of Medical Genetics. 2003 July 30; 120A(3): 350-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838554

•

Vitamin D and related research in osteogenesis imperfecta. Author(s): Sbyrakis S, Mengreli C, Cote GB, Morakis A. Source: Prog Clin Biol Res. 1982; 104: 367-76. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6298814

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•

Vitamin D metabolism in osteogenesis imperfecta during calcitonin therapy. Author(s): Nishi Y, Hyodo S, Yoshimitsu K, Sawano K, Yamaoka K, Seino Y, Usui T. Source: Pediatrics. 1984 April; 73(4): 538-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6546792

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Williams' rods: insertion for osteogenesis imperfecta. Author(s): Gray D. Source: Nurs Times. 1973 November 22; 69(47): 1560-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4774875

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CHAPTER 2. NUTRITION AND OSTEOGENESIS IMPERFECTA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and osteogenesis imperfecta.

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

7

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

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

BiP binds type I procollagen pro alpha chains with mutations in the carboxylterminal propeptide synthesized by cells from patients with osteogenesis imperfecta. Author(s): Department of Pathology, University of Washington, Seattle 98195. Source: Chessler, S D Byers, P H J-Biol-Chem. 1993 August 25; 268(24): 18226-33 00219258

•

Cell proliferation of human fibroblasts and osteoblasts in osteogenesis imperfecta: influence of age. Author(s): Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Source: Fedarko, N S D'Avis, P Frazier, C R Burrill, M J Fergusson, V Tayback, M Sponseller, P D Shapiro, J R J-Bone-Miner-Res. 1995 November; 10(11): 1705-12 08840431

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Collagen chemistry and the brittle bone diseases. Source: Paterson, C R Endeavour. 1988; 12(2): 56-9 0160-9327

•

Direct visualization of affected collagen molecules synthesized by cultured fibroblasts from an osteogenesis imperfecta patient. Author(s): Department of Anatomy, Nagoya University School of Medicine, Japan. Source: Kobayashi, K Hata, R Nagai, S Niwa, J Hoshino, T Biochem-Biophys-ResCommun. 1990 October 15; 172(1): 217-22 0006-291X

•

Effects of synthetic salmon calcitonin therapy in children with osteogenesis imperfecta. Author(s): Department of Pediatrics, Dona Estefania Hospital, Lisbon, Portugal. Source: Rebelo, I da Silva, L P Blanco, J C Monteiro, M E Ferreira, N C J-Int-Med-Res. 1989 Jul-August; 17(4): 401-5 0300-0605

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Elevated accumulation of hyaluronate in the tubular bones of osteogenesis imperfecta. Author(s): Department of Embryology, Institute for Developmental Research, Kasugai, Japan. Source: Oohira, A Nogami, H Bone. 1989; 10(6): 409-13 8756-3282

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Hypercalciuria in children severely affected with osteogenesis imperfecta. Author(s): Metabolic Research Unit, Shriners Hospital for Crippled Children, St. Louis, MO 63131. Source: Chines, A Petersen, D J Schranck, F W Whyte, M P J-Pediatr. 1991 July; 119(1 ( Pt 1)): 51-7 0022-3476

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Hypertrophic callus formation leading to high-output cardiac failure in a patient with osteogenesis imperfecta. Author(s): Department of Orthopaedic Surgery, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland. Source: Burke, T E Crerand, S J Dowling, F J-Pediatr-Orthopage 1988 Sep-October; 8(5): 605-8 0271-6798

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Mineralized tissue protein profiles in the Australian form of bovine osteogenesis imperfecta. Source: Fisher, L.W. Denholm, L.J. Conn, K.M. Termine, J.D. Calcif-Tissue-Int. New York, N.Y. : Springer International. January 1986. volume 38 (1) page 16-20. ill. 0171967X

Nutrition

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Osteogenesis imperfecta and other bone disorders in the differential diagnosis of unexplained fractures. Author(s): Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee. Source: Paterson, C R J-R-Soc-Med. 1990 February; 83(2): 72-4 0141-0768

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The growth hormone and somatomedin axis in short children with osteogenesis imperfecta. Author(s): Human Genetics Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Source: Marini, J C Bordenick, S Heavner, G Rose, S Hintz, R Rosenfeld, R Chrousos, G P J-Clin-Endocrinol-Metab. 1993 January; 76(1): 251-6 0021-972X

•

The retention of abnormal type I procollagen and correlated expression of HSP 47 in fibroblasts from a patient with lethal osteogenesis imperfecta. Author(s): Department of Orthopedic Surgery, Nagoya University School of Medicine, Japan. Source: Kojima, T Miyaishi, O Saga, S Ishiguro, N Tsutsui, Y Iwata, H J-Pathol. 1998 February; 184(2): 212-8 0022-3417

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND OSTEOGENESIS IMPERFECTA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to osteogenesis imperfecta. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to osteogenesis imperfecta and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “osteogenesis imperfecta” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to osteogenesis imperfecta: •

A clinical and ultrastructural study of osteogenesis imperfecta after flavonoid (Catergen) therapy. Author(s): Jones CJ, Cummings C, Ball J, Beighton P. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1984 December 15; 66(24): 907-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6505901

•

A variable pulse-burst electromagnetic generator for electrical stimulation of biological systems. Author(s): Reddy GN, Saha S. Source: J Biomed Eng. 1983 October; 5(4): 336-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6632846

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Advances in osteogenesis imperfecta. Author(s): Cole WG. Source: Clinical Orthopaedics and Related Research. 2002 August; (401): 6-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151877

•

Approaches for skeletal gene therapy. Author(s): Niyibizi C, Wallach CJ, Mi Z, Robbins PD. Source: Critical Reviews in Eukaryotic Gene Expression. 2002; 12(3): 163-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12449341

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Bone tissue composition: biochemical anatomy of bone. Author(s): Aerssens J, Dequeker J, Mbuyi-Muamba JM. Source: Clinical Rheumatology. 1994 December; 13 Suppl 1: 54-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7750243

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Demineralization of dentin with EDTA in organic solvent: immunofluorescence of collagen in osteogenesis imperfecta and normal teeth. Author(s): Lukinmaa PL, Ranta H, Ranta K, Peltonen L, Hietanen J. Source: Coll Relat Res. 1985 December; 5(6): 505-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3938691

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Evidence for abnormality of bone-matrix proteins in osteogenesis imperfecta. Author(s): Dickson IR, Millar EA, Veis A. Source: Lancet. 1975 September 27; 2(7935): 586-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=51410

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Future potentials for using osteogenic stem cells and biomaterials in orthopedics. Author(s): Oreffo RO, Triffitt JT. Source: Bone. 1999 August; 25(2 Suppl): 5S-9S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458266

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Hearing loss in children with osteogenesis imperfecta. Author(s): Kuurila K, Grenman R, Johansson R, Kaitila I. Source: European Journal of Pediatrics. 2000 July; 159(7): 515-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923226

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High proportion of mutant osteoblasts is compatible with normal skeletal function in mosaic carriers of osteogenesis imperfecta. Author(s): Cabral WA, Marini JC.

Alternative Medicine 77

Source: American Journal of Human Genetics. 2004 April; 74(4): 752-60. Epub 2004 March 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15024692 •

Intrauterine stem cell therapy. Author(s): Fisk NM, Chan J, O'Donoghue K. Source: Ann Acad Med Singapore. 2003 September; 32(5 Suppl): S8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968717

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Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Author(s): Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 June 25; 99(13): 8932-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084934

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Marrow mesenchymal cell transplantation for genetic disorders of bone. Author(s): Horwitz EM. Source: Cytotherapy. 2001; 3(5): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11953021

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Osteogenesis imperfecta in a weightlifter. Author(s): Yochum TR, Kulbaba S, Seibert RE. Source: Journal of Manipulative and Physiological Therapeutics. 2002 June; 25(5): 334-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072856

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Osteogenesis imperfecta: fibronectin in dentin matrix. Author(s): Lukinmaa PL, Ranta H, Vaheri A. Source: Journal of Craniofacial Genetics and Developmental Biology. 1988; 8(1): 75-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3062036

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Osteogenesis imperfecta: morphological, histochemical and biochemical aspects. Modifications induced by (+)-catechin. Author(s): Cetta G, Lenzi L, Rizzotti M, Ruggeri A, Valli M, Boni M. Source: Connective Tissue Research. 1977; 5(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=141362

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Paraplegia in osteogenesis imperfecta. A case report. Author(s): Ziv I, Rang M, Hoffman HJ.

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Source: The Journal of Bone and Joint Surgery. British Volume. 1983 March; 65(2): 184-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6826628 •

Potential of gene therapy for treating osteogenesis imperfecta. Author(s): Niyibizi C, Smith P, Mi Z, Robbins P, Evans C. Source: Clinical Orthopaedics and Related Research. 2000 October; (379 Suppl): S126-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11039761

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Vitamin C supplementation and relief from pain. A review and interpretation. Author(s): Ringsdorf WM Jr. Source: J Ala Dent Assoc. 1984 Fall; 68(4): 47-53. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6238986

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What families with children with brittle bones want to tell. Author(s): Bernehall Claesson I, Brodin J. Source: Child: Care, Health and Development. 2002 July; 28(4): 309-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211190

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

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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•

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

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

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

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

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

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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

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

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

Alternative Medicine 79

The following is a specific Web list relating to osteogenesis imperfecta; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com

•

Alternative Therapy Aston-Patterning Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10118,00.html

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

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CHAPTER 4. IMPERFECTA

DISSERTATIONS

ON

OSTEOGENESIS

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

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

Collagen Metabolism by Fibroblasts from Normals and Individuals with Osteogenesis Imperfecta by Fraser, Judith; PhD from Mcgill University (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK51955

•

Pregnancy in Women with Osteogenesis Imperfecta Type III and Type IV: Obstetrical Issues, Pregnancy Management, Outcomes and Psychosocial Aspects by Shea, Tara Jean; MS from Sarah Lawrence College, 2003, 80 pages http://wwwlib.umi.com/dissertations/fullcit/1413595

•

The Classification of Osteogenesis Imperfecta As Elicited by Multivariate Cluster Analysis by Ward, Richard E., PhD from University of Colorado at Boulder, 1980, 161 pages http://wwwlib.umi.com/dissertations/fullcit/8114019

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

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

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

Bisphosphonate Treatment of Osteogenesis Imperfecta Condition(s): Osteogenesis Imperfecta Study Status: This study is currently recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: The primary purpose of this trial is to evaluate whether the investigational medication is safe, effective and has the ability to increase spine bone density in osteogenesis imperfecta (OI) patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063479

•

Evaluation and Intervention for the Effects of Osteogenesis Imperfecta Condition(s): Dwarfism; Osteogenesis Imperfecta Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD)

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: Osteogenesis Imperfecta is a genetic disorder occurring in children causing abnormally fragile bones. Patient's with osteogenesis imperfecta often suffer fractures from minimal trauma. These patient's can have deformities of long bones, blueness of the white portion of the eye (sclerae), weak ligaments, and deafness due to diseased bones in the inner ear (otosclerosis). Growth deficiency is a hallmark feature of Osteogenesis Imperfecta. Growth patterns have been defined for some of the different types of Osteogenesis Imperfecta. At about 1 year of age, children with Types III and IV Osteogenesis Imperfecta show a predictable leveling off (plateau) of their growth rate. Children with Type IV Osteogenesis Imperfecta begin to resume normal growth rate at about four to five years, but they will not "catch up" to a normal height. Children with Osteogenesis Imperfecta Type III will remain at a leveled off growth rate. The reason for the leveling off (plateau) of the growth rate is unknown. The purposes of this study will concentrate on four areas of research; genetics, rehabilitation, growth, and the natural history of the multiple secondary features of Osteogenesis Imperfecta. This study will be broken up into 2 steps or phases. Phase I will focus on children from birth to age 5, and Phase II will concentrate on children ages 5 - 18 years. One of the objectives in Phase I will be to determine the effects of long leg bracing in children with osteogenesis imperfecta. The study will observe the patient's ability to do activities while standing upright as well as the development of manual skills. In addition the study will observe the alignment of the patient's bones and the bone strength and density. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001594 •

Growth Hormone Therapy in Osteogenesis Imperfecta Condition(s): Dwarfism; Osteogenesis Imperfecta Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Growth deficiency is a key feature of severe Osteogenesis Imperfecta (OI) and a frequent feature of mild to moderate forms of the disease. The reason that children with OI are short is not fully understood. We do know that details such as the number of fractures suffered or the type of OI do not fully explain the short stature of OI. Growth patterns have been defined for children with OI Types I, III, and IV. At about 12 months of age, children with Types III and IV OI demonstrate a predictable plateau of their linear growth rate. Type IV OI children begin to resume a normal growth rate at about age four to five years, but they will not "catch up" to a normal height, as they have "lost" a significant period of growth. The plateau usually continues for children with Type III OI. The reason for this growth plateau is unknown. There have been no studies which evaluate the growth of OI children in this age range. Our previous studies of growth in OI children have begun at age 5 years. We have studied growth in OI children for the past 10 years. Different medications have been tried to both stimulate growth and improve bone density. Some children have responded to growth hormone (their growth rate increased by at least 50%) and some did not. The majority of children who did respond were Type IV. However, we need to carefully treat and study more children to try to determine which children will benefit from growth hormone medication. The Goals of this Study Are: 1. We want to try to find a cause for the growth plateau common in types III and IV OI. Long-term, our goal is to develop a treatment to eliminate this plateau. 2. We want to see how long and how well

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OI bone will respond to growth stimulation. 3. We hope to find a "predictor" for who will respond to growth hormone and who will not, by measuring your child's endocrine and growth hormone function before receiving any growth hormone treatment. 4. We want to measure the effects of growth stimulation on bone density, and the quality of OI bone. 5. We want to see if there are long term benefits resulting from this treatment in the form of final adult height, trunk height, and possibly improved function of the respiratory system. Median Subject Age (on p. 1 of webpage): 1-15 years (replaces 0-20) Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001305 •

Pamidronate to Treat Osteogenesis Imperfecta in Children Condition(s): Osteogenesis Imperfecta Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This study will evaluate the effect of pamidronate-a drug that decreases bone resorption (breakdown)-on osteogenesis imperfecta. This is a genetic disorder of collagen, the major protein in bone. The abnormal collagen causes weak bones, and children with severe osteogenesis imperfecta sustain many fractures throughout their lives. They also have growth deficiency, curvature of the spine, crumbling teeth, hearing loss, easy bruising and heart and lung problems. The study will compare bone density, quality and strength, final adult height, trunk height, and functional ability in children who receive 1) pamidronate every 3 months, 2) tpamidronate every 3 months + growth hormone injections, 3) pamidronate every 6 months, or 4) pamidronate every 6 months + growth hormone injections. Children 2 years of age and older with severe osteogenesis imperfecta (types III and IV) may be eligible for this study. Those enrolled will be randomly assigned to groups according to age; children two to four years of age will be randomly assigned to receive pamidronate every 3 or every 6 months. Children four years of age and older may participate in the growth hormone treatment groups. These children will continue on growth hormone until they reach their adult height or fail to grow as much as would be expected for someone on growth hormone. Patients will be followed in the clinic every 3 months for a history, physical examination, X-rays, blood tests, and measurements (weight, head circumference, and bone lengths). Children will receive a 3 to 4 hour infusion of pamidronate through an intravenous catheter (thin flexible tube placed in a vein) once a day for 3 days each visit. (Once inserted, the catheter is left in place to avoid multiple needle sticks for administering the drug and collecting blood samples.) Children who are taking growth hormone will be given the drug at the first treatment visit. At that time, the accompanying parent will be instructed on how to mix the drug and give injections. The child receives an injection 6 days a week (Sunday off). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005901

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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 “osteogenesis imperfecta” (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/

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

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

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

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

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

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

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

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

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

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

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•

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

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

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CHAPTER 6. PATENTS ON OSTEOGENESIS IMPERFECTA 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 “osteogenesis imperfecta” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on osteogenesis imperfecta, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Osteogenesis Imperfecta By performing a patent search focusing on osteogenesis imperfecta, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on osteogenesis imperfecta: •

Compositions and methods for detecting altered COL1A1 gene sequences Inventor(s): Ala-Kokko; Leena (Oulu, FI), Annunen; Susanna (Oulu, FI), Colige; Alain (Philadelphia, PA), Deltas; Constantinos D. (Nicosia, CY), Early; James (Upper Darby, PA), Korkko; Jarmo (Philadelphia, PA), Paassilta; Petteri (Oulu, FI), Pack; Michael (Philadelphia, PA), Pihlajamaa; Tero (Oulu, FI), Prockop; Darwin J. (Philadelphia, PA), Sereda; Larisa (Philadelphia, PA), Spotila; Loretta D. (Haddonfield, NJ), Vuoristo; Mirko (Oulu, FI), Westerhausen Larson; Andrea (Forrest Hills, PA) Assignee(s): Allegheny University of the Health Sciences (philadelphia, Pa), Thomas Jefferson University (philadelphia, Pa), University of Oulu (oulu, Fi) Patent Number: 6,265,157 Date filed: October 3, 1997 Abstract: Compositions and methods useful for determining whether a subject has an alteration in a gene encoding a protein chain of Type I or Type IX collagen are described. Novel intronic sequences of five human genes, COL1A1, COL1A2, COL9A1, COL9A2, and COL9A3 are described. Methods of determining the existence in a subject of a pathological condition associated with an altered gene encoding a Type I or Type IX collagen protein chain are provided, wherein such pathological conditions include diseases and disorders which are known to be associated with an altered gene encoding a Type I or Type IX collagen protein chain. Primers, probes, and methods of detecting a genetic predisposition of a subject for a pathological condition associated with an altered gene encoding a Type I or Type IX collagen protein chain are provided. Diseases and disorders for which the methods and compositions of the invention are useful for diagnostic or prognostic purposes include, but are not limited to osteoporosis, osteoarthritis, chondrodysplasia, multiple epiphyseal dysplasia, osteogenesis imperfecta, shortness of stature, scoliosis, low bone density, and degenerative joint disease. Excerpt(s): The field of the invention is detecting altered collagen gene sequences. The collagen genes are an important family of genes, the products of which provide the extracellular framework for virtually all multicellular organisms (Bornstein et al., 1980 Ann. Rev. Biochem. 49:957-1003). More than nineteen distinct types of collagen have been described (Ramirez et al., 1985, Ann. New York Acad. Sci. 460:117-129; Vuorio et al., 1990, Annu. Rev. Biochem. 59:837-872; Chu et al., 1993, In: Connective Tissue and Its Heritable Disorders, Royce et al., eds., Wiley-Liss, New York, pp.149-165; Prockop et al., 1995, Annu. Rev. Biochem. 64:403-434). The biosynthesis of collagen has been described (Prockop et al., 1979, N. Eng. J. Med. 301:13-23). Large collagen structures form by nucleated growth of collagen chains into triple helical collagen subunits. Collagen fibrils form by nucleated growth of collagen subunits, a fibril comprising a quarter-staggered array of subunits (Gross et al., 1958, Annu. Rev. Cell Biol. 2:421-457; Wood et al., 1960, Biochem. J. 75:588:598; Prockop et al., 1984, N. Eng. J. Med. 311:376-386; Kadler et al., 1987, J. Biol. Chem. 262:15696-15701; Na et al., 1989, Biochem. 28: 7153-7161; Kadler et al., 1990, Biochem. J. 268:339-343; Prockop et al., 1989, Biophysics (Eng. Transl. Biofizika) 3:81-89). During nucleated growth, the collagen protein chains fold into the triple helical conformation that is a unique and characteristic feature of all collagens (Engel, 1987, Adv. Meat. Res. 4:145-158; Engel et al., 1991, Annu. Rev. Biophys. Biophys. Chem.

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20:137-152; Piez, 1984, In: Extracellular Matrix Biochemistry, Piez et al., eds., Elsevier Science Pub. Co. Inc., New York, pp. 1-40). Web site: http://www.delphion.com/details?pn=US06265157__ •

Gene transfer into bone cells and tissues Inventor(s): Bonadio; Jeffrey (Ann Arbor, MI), Goldstein; Steven A. (Ann Arbor, MI) Assignee(s): The Regent of the University of Michigan (ann Arbor, Mi) Patent Number: 5,763,416 Date filed: February 18, 1994 Abstract: Disclosed are methods, compositions and devices for use in transferring nucleic acids into bone cells in situ. The transfer of an osteotropic gene into bone progenitor cells is described, which event is shown to stimulate the progenitor cells and to promote bone growth, repair and regeneration in vivo. These gene transfer protocols are suitable for use in transferring various nucleic acid materials into bone, and have many uses, for example, in treating various bone-related diseases and defects, such as, in promoting fracture repair, use in connection with implants, and in treating osteoporosis and osteogenesis imperfecta. Excerpt(s): The present invention relates generally to the field of bone cells and tissues and, more particularly, it concerns the transfer of genetic material into bone. In certain examples, the invention concerns the use of nucleic acids to stimulate bone growth, repair and regeneration. Methods, compositions and devices are provided for transferring an osteotropic gene into bone progenitor cells, which is shown to stimulate progenitor cells and to promote increased bone formation in vivo. This invention may be used to administer nucleic acids to bone tissue in many circumstances, including the treatment of a variety of diseases, from promoting fracture repair and bone reconstruction, to treating osteoporosis and osteogenesis imperfecta. Defects in the process of bone repair and regeneration are linked to the development of several human diseases and disorders, e.g., osteoporosis and osteogenesis imperfecta. Failure of the bone repair mechanism is, of course, also associated with significant complications in clinical orthopaedic practice, for example, fibrous non-union following bone fracture, implant interface failures and large allograft failures. The lives of many individuals would be improved by the development of new therapies designed to stimulate and strengthen the fracture repair process. Naturally, any new technique to stimulate bone repair would be a valuable tool in treating bone fractures. A significant portion of fractured bones are still treated by casting, allowing natural mechanisms to effect wound repair. Although there have been advances in fracture treatment in recent years, including improved devices, the development of new processes to stimulate, or complement, the wound repair mechanisms would represent significant progress in this area. Web site: http://www.delphion.com/details?pn=US05763416__

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•


Transgenic mice expressing a mutated human collagen gene Inventor(s): Ala-Kokko; Leena (Philadelphia, PA), Helminen; Heikki (Philadelphia, PA), Khillan; Jaspal S. (Philadelphia, PA), Kontusaari; Sirpa (Oulu, FI), Olsen; Anne (Moraga, CA), Prockop; Darwin J. (Philadelphia, PA), Sokolov; Boris (Philadelphia, PA), Vandenberg; Philipp (Philadelphia, PA) Assignee(s): Thomas Jefferson University (philadelphia, Pa) Patent Number: 5,663,482 Date filed: March 16, 1994 Abstract: The invention is transgenic mice substantially all of whose cells contain a mutated human collagen gene. Methods for testing therapies for the treatment of osteogenesis imperfecta, osteoporosis, and chondrodysplasia are provided. Excerpt(s): This invention was made in the course of research supported in part by NIH grants AR31888 and AR39740. The Government has certain rights in this invention. U.S. Pat. No. 4,736,866 (Leder et al.) discloses a transgenic non-human eukaryotic animal, preferably a mouse, whose germ cells and somatic cells contain an activated oncogene sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage. In a preferred embodiment, the chromosome of the transgenic animal includes an endogenous coding sequence, most preferably the c-myc gene, which is substantially the same as the oncogene sequence. Transcription of the oncogene sequence is under the control of a promoter sequence different from the promoter sequence controlling transcription of the endogenous coding sequence or under the control of a synthetic promoter sequence. Gene fusions were made using the mouse myc gene and the MMTV LTR. The MMTV-myc plasmids were digested with SalI and EcoRI and separately injected into the male pronuclei of fertilized one-cell mouse eggs. The injected eggs were then transferred to pseudopregnant mice and allowed to develop to term. At 4 weeks of age, each pup born was analyzed using DNA taken from the tail in a Southern blot analysis. The Southern blot hybridizations showed that some of the founder mice retained the injected MMTV-myc fusion. The founder animals were then mated to uninjected animals and DNA of the resulting lines of transgenic offspring was analyzed. It was found that several lines of mice carried the MMTV-myc fusion. It is taught that the animals of the invention can be used to test a material suspected of being a carcinogen by exposing the animal to the material and determining neoplastic growth as an indicator of carcinogenicity. It is also taught that the invention can be used as tester animals for materials thought to confer protection against neoplasms. Stacey et al., Nature, 332: 131-136 (1988) disclose transgenic mice bearing an engineered mutant pro.alpha.1(I) collagen gene. Two mutations were produced in a mouse COL1A1 genomic clone, both of which resulted in a substitution of a glycine residue at position 859 of the.alpha. 1(I) chain by either a cysteine or an arginine. Mutagenesis of the cloned gene was carried out by replacement of the wild-type DNA region between BstEII and SfiI restriction sites at positions 2623 and 2641 by double stranded synthetic oligodeoxyribonucleotides. The final constructs contained the complete coding region of the gene linked to one of four promoters: one-kilobase (kb), 2.5-kb and 3.7-kb fragments 5' of the mouse COLIA coding region, or the Maloney murine leukemia virus long terminal repeat promoter region. The mutant constructs were transferred into either NIH3T3 fibroblasts or into Mov13 homozygous fibroblasts which do not express the pro.alpha.1(I) collagen chain. Cultured cells expressing the mutant constructs produced type I collagen with the same biochemical characteristics as mutant collagens produced by cells from patients with perinatal lethal osteogenesis imperfecta. To determine whether the mutant constructs would generate a dominant phenotype similar to the

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human disease, DNA from the 3.7 kb-promoter Gly-Cys mutant cosmid was microinjected into fertilized eggs which were allowed to complete development in utero. It was found that none of the mice surviving birth was positive for the transgene. In contrast, almost all of the fetuses which died shortly before or after delivery carried copies of the mutant gene suggesting that the mutant gene exerts a dominant lethal effect. Web site: http://www.delphion.com/details?pn=US05663482__

Patent Applications on Osteogenesis Imperfecta 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 osteogenesis imperfecta: •

Use of statins to inhibit formation of osteoclasts Inventor(s): Baragi, Vijaykumar Mahalingappa; (Ann Arbor, MI), Devalaraja, Radhika; (Ann Arbor, MI), Peters, Brandon R.; (Fraser, MI), Renkiewicz, Richard Raymond; (Novi, MI) Correspondence: Francis J. Tinney; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030055101 Date filed: September 10, 2002 Abstract: A method for inhibiting the formation of osteoclasts comprising administering a therapeutically effective amount of a statin to a mammal in need thereof as well as pharmaceutical compositions, kits for containing such compositions comprising a statin or a method of treating or preventing a disease state selected from the group consisting of: osteoporosis, Paget's disease, osteolysis, hypercalcemia of malignancy, osteogenesis imperfecta, osteoarthritis, alveolar bone loss, side effects of immunosuppressive therapy, and side effects of chronic glucocorticoid use by inhibiting the formation of osteoclasts comprising administering a therapeutically effective amount of a statin to a mammal in need thereof. Excerpt(s): The present invention relates to the use of statins to inhibit the formation of osteoclasts, in particular, the use of atorvastatin to inhibit the formation of osteoclasts as well as pharmaceutical compositions, kits for containing such compositions comprising a statin and a method of treating or preventing a disease, such as, for example, osteoporosis, Paget's disease, osteolysis, hypercalcemia of malignancy, osteogenesis imperfecta, osteoarthritis, alveolar bone loss, and side effects of immunosuppressive therapy and chronic glucocorticoid use by inhibiting formation of osteoclasts. Maintenance of bone density is a dynamic process wherein osteoclasts resorb and osteoblasts resynthesize the bone, Parfitt A M, Riggs B L, Melton L J, Osteoporosis: etiology, diagnosis and management, New York: Raven Press, 1988;13:501. An imbalance between resorption and formation leads to bone loss, in conditions such as osteoporosis and Paget's disease. Other conditions and diseases affected by this imbalance include osteolysis, hypercalcemia of malignancy, osteogenesis imperfecta,

10

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

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osteoarthritis, alveolar bone loss or side effects of immunosuppressive therapy and chronic glucocorticoid use. The bone loss is partly a consequence of enhanced osteoclastogenesis--a series of events that includes differentiation, migration, fusion, and survival of osteoclasts. Osteoclasts, the multinucleated giant cells, develop from hematopoietic cells of macrophage lineage as a result of increased production of osteoclastogenic cytokines by osteoblasts/stromal cells, Suda T, Takahashi N, Martin T J, Modulation of osteoclast differentiation, Endocr. Rev., 1992;13:66-80; Chambers T J, Revell P A, Fuller K, Athanasou N A, Resorption of bone by isolated rabbit osteoclasts, J. Cell Sci., 1984;66:383-399; Takahashi N, Udagawa N, Suda T, A new member of TNF ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function, Biochem. Biophys. Res. Commun., 1999;256:449-455; and Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie M T, Martin T J, Modulation of osteoclast differentiation and function by the new members of the TNF receptor and ligand families. Endocr. Rev., 1999;20:345-357. Of the various osteoclastogenic cytokines, macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL) are considered to be essential for osteoclast development, Jimi E, et al., Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact, Endocrinology, 1996;137:2187-2190; and Lacey D, et al., Osteoprotegerin ligand murine osteoclast survival in vitro and in vivo, Am. J. Pathol., 2000;157:435-448. Several different therapeutic agents have been used to treat bone loss associated with osteoporosis; however, little is known about their mechanism of action. Recent studies indicate that perturbation of the cholesterol biosynthetic pathway has a direct effect on osteoclasts. Nitrogen-containing bisphosphonates, for example, are reported to inhibit formation and promote apoptosis of osteoclasts by preventing protein prenylation, a rate-limiting step in the cholesterol biosynthesis pathway, Cummings S, Bauer D C, Do statins prevent both cardiovascular disease and fracture?, J. Am. Med. Assoc., 2000;283:3255-3257; Wang P S, Solomon D H, Mogun H, Avorn J, HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients, J. Am. Med. Assoc., 2000;283:321 1-3216; Meier C R, Schlienger R G, Kraenzlin M E, Schlegel B, Hershel J, HMG-CoA reductase inhibitors and the risk of fractures, J. Am. Med. Assoc., 2000;283:3205-3210; Russell R G, Rogers M J, Frith J C, et al., The pharmacology of bisphosphanates and new insights into their mechanisms of action, J. Bone Miner Res., 1999;14:53-65; Reszka A A, Halasy-Nagy J M, Masarachia P J, Rodan G A, Bisphosphanates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis: a link between inhibition of the mevalonate pathway and regulation of apoptosis-promoting kinase. J. Biol. Chem., 1999;274:34967-34973. Inhibition of HMGCoA reductase, an early step in the cholesterol biosynthesis, by statins would be expected to have similar effects on osteoclasts. On the contrary, Mundy G, et al., Stimulation of bone formation in vitro and in rodents by statins, Science, 999;286: 194649 have shown that administration of statins in vivo increases bone morphogenic protein-2 (BMP-2) levels, which in turn results in increased bone formation. Similarly, simvastatin and lovastatin were reported to stimulate a greater dose-dependent increase in total bone area compared to established growth factors such as BMP-2 or basal fibroblast growth factor (b-FGF) in both normal and ovariectomized (OVX) rats (see U.S. Pat. No. 6,022,887). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with osteogenesis imperfecta, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “osteogenesis imperfecta” (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 osteogenesis imperfecta. You can also use this procedure to view pending patent applications concerning osteogenesis imperfecta. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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

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

Living With Osteogenesis Imperfecta: A Guidebook for Families Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1994. 299 p. Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: $25.00 plus shipping and handling. Summary: This guidebook provides people who have osteogenesis imperfecta (OI) and their caregivers with practical advice for living with this disorder, which is characterized by bones that break easily because of imperfectly formed collagen. Part one focuses on medical issues, including normal and abnormal bone formation; the clinical features of OI; prenatal counseling; diagnosis; pregnancy; the nutritional needs of children with OI; and rehabilitation management of the child with OI. Other medical concerns deal with the clinical manifestations and treatment of dental problems, hearing

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impairment, spinal curvature, nonpharmacologic and pharmacologic pain control options, intramedullary rodding, additional complications, and OI research. Part two addresses educational and social concerns, including understanding the psychology of OI within the family; developing self-esteem; having an intimate relationship; educating children and youth with OI; handling false allegations of child abuse; understanding the concerns of people with milder OI; living independently; and deciding to become an adoptive or biological parent. Part three presents guidelines on living with OI. Topics include coping with the first weeks of life with a child who has severe OI; handling the infant or child who has OI; dealing with fractures; caring for a fracture and a cast; participating in physical activities and exercise programs; selecting toys and clothing for children with OI; selecting and adapting equipment and environments; and dealing with travel. In addition, the guidebook provides information on the OI Foundation. 6 appendices and numerous figures and references. •

Managing Osteogenesis Imperfecta: A Medical Manual Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1997. 220 p. Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: $25.00 plus shipping and handling. Summary: This manual for health professionals, people who have osteogenesis imperfecta (OI), and parents of children who have OI provides information on its medical management. Chapter one serves as an introduction, focusing on the genetics of OI, its signs and symptoms, anesthetic care, child abuse, and recommendations for checkups. The next chapter provides information on normal bone development, bone in OI, and treatment. Chapters three and four focus on imaging methods and characteristics. Chapter five describes treating fractures and focuses on cast application, care, and removal. This is followed by a chapter on the surgical management of with intramedullary rod fixation. Chapter seven examines the relationship between OI and osteoporosis, while chapter eight details the aspects of a total fitness program, including aerobic conditioning, muscle strengthening and stretching, and skill- related activities. Topics discussed in chapters nine through 11 include the intrapartum management of a patient with OI, prenatal and clinical diagnosis, and care of a newborn with severe OI. Chapters on developmental and educational issues, the use of growth hormone therapy, and obstacles to motor performance and interventions to minimize or compensate for them follow. Chapters 15 through 19 discuss dental care, cardiovascular manifestations and their treatment, care of the feet, evaluation and treatment of hearing loss, and osteoarthritis. The final two chapters highlight some of the psychological ramifications of having a person with OI in a family and discuss types of pain and pain management. 5 appendices, 4 tables, and numerous figures and references.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “osteogenesis imperfecta” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “osteogenesis imperfecta” (or a

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synonym) in their titles. The following is indicative of the results you might find when searching for “osteogenesis imperfecta” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Living With Osteogenesis Imperfecta: A Guidebook for Families by Heidi C. Glauser (Editor); ISBN: 0964218909; http://www.amazon.com/exec/obidos/ASIN/0964218909/icongroupinterna

•

Managing Osteogenesis Imperfecta: A Medical Manual by Pricisalla, MD Wacaster (Editor); ISBN: 0964218933; http://www.amazon.com/exec/obidos/ASIN/0964218933/icongroupinterna

•

The Brittle Bone Syndrome: Osteogenesis Imperfecta by Roger Smith, et al; ISBN: 0407002111; http://www.amazon.com/exec/obidos/ASIN/0407002111/icongroupinterna

•

The Official Patient's Sourcebook on Osteogenesis Imperfecta: A Revised and Updated Directory for the Internet Age by Icon Health Publications; ISBN: 0597833990; http://www.amazon.com/exec/obidos/ASIN/0597833990/icongroupinterna

•

Third International Conference on Osteogenesis Imperfecta; ISBN: 0897664833; http://www.amazon.com/exec/obidos/ASIN/0897664833/icongroupinterna

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Third International Conference on Osteogenesis Imperfecta (Annals of the New York Academy of Sciences, Vol 543) by Giuseppe Cetta, et al; ISBN: 0897664825; http://www.amazon.com/exec/obidos/ASIN/0897664825/icongroupinterna

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

Temporal Bone Granulomas and Dystrophies Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 801-811. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: Granulomatous disease and osteodystrophy are a diverse group of disorders that include osseous dysplasia, histiocytic proliferation, autoimmune disorders, and infectious diseases. This chapter on temporal bone granulomas and dystrophies is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. The authors discuss osteodystrophies and dysplasias, including Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, osteopetrosis,

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endosteal hyperostosis, and osteitis fibrosa cystica; histiocytic proliferation, notably Langerhans cell histiocytosis; and autoimmune disorders, including Wegener's granulomatosis and sarcoidosis. The authors note that most of these processes are not common, but they are important to otolaryngologists. Local behavior can be aggressive, and audiologic, vestibular, or facial nerve dysfunction can result. 5 figures. 1 table. 73 references. •

Auditory Dysfunction in Genetic Disorders of the Skeleton Source: in Martini, A.; Read, A.; Stephens, D., eds. Genetics and Hearing Impairment. San Diego, CA: Singular Publishing Group, Inc. 1996. p. 130-140. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $54.00 plus shipping and handling. ISBN: 1565937929. Summary: Hearing impairment is a component of a large number of genetic disorders in which the skeleton is primarily involved. This chapter exploring auditory dysfunction in genetic disorders of the skeleton is from a book that offers an overview of genetic hearing loss for audiologists, otolaryngologists, and clinical geneticists. The author reviews the main categories of genetic skeletal disorders in which involvement of the hearing mechanism is an important feature, including sclerosing bone dysplasia, dwarfing skeletal dysplasia, osteogenesis imperfecta, mucopolysaccharidoses, craniofacial malformation syndromes, and miscellaneous skeletal disorders. The author notes that the fact that the auditory dysfunction is predominantly a conductive one in many of the genetic skeletal conditions, and a sensorineural or mixed dysfunction in others has important implications for treatment. 5 figures. 2 tables.

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Otosclerosis Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 467-487. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: Otosclerosis is a bone disease limited to the temporal bone and primarily affecting the otic capsule. The growth of spongy bone usually results in stapes fixation but may also involve the cochlea and other parts of the labyrinth. This chapter on the clinical features of otosclerosis is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. Topics include definition; historical perspective; epidemiology; pathogenesis; pathology; history and physical findings; audiometry, including tuning fork tests, standard audiometry, the Carhart notch, and acoustic impedance; radiographic studies; differential diagnosis; medical management; surgical management, including candidate selection and preoperative management; surgical techniques, including stapedioplasty, stapedectomy, stapedotomy, laser stapedectomy, bilateral stapedectomy, closure, and postoperative care; intraoperative problems and complications, including intraoperative vertigo(dizziness), tympanic membrane (eardrum) perforation, obliterative otosclerosis, cerebrospinal fluid otorrhea (fluid from the ear), dehiscence of the facial nerve, floating footplate, and subluxation of the incus; postoperative complications, including vertigo,

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tinnitus (ringing or other sounds in the ears), cochlear hearing loss, facial paralysis, otitis media (middle ear infection), taste disturbance and oral dryness, perilymph fistula, incus necrosis, middle ear fibrosis, granuloma, postoperative labyrinthitis, meningitis, and recurrence; the evaluation of the results of stapes surgery; results of primary stapes surgery; stapedectomy (removal of the stapes of the middle ear and insertion of a graft and prosthesis) in children; revision stapedectomy; fenestration (surgical opening) and postfenestration stapedectomy; nonotosclerotic lesions of the stapes, including Paget's disease, osteogenesis imperfecta, tympanosclerosis, and degenerative arthritis; and other causes of ossicular fixation, including lateral ossicular fixation and incus annulus fusion. 31 figures. 112 references. •

Molecular Abnormalities of Collagen Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 1. New York, NY: Oxford University Press, Inc. 1993. p. 204-232. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals focuses on molecular abnormalities of collagen. The molecular analysis of human genetic disease is explained. Gene analysis of collagen is described. Collagen folding and self-assembly is discussed. Mutations of collagen genes and proteins are detailed. These mutations include type I collagen mutations that cause osteogenesis imperfecta and Ehlers-Danlos syndrome type VII; type II collagen mutations that cause chondrodystrophies such as spondyloepiphyseal dysplasia congenita, achondrogenesis, and hereditary osteoarthritis; type III collagen mutations that cause Ehlers-Danlos syndrome III and IV; and abnormalities of collagen type VII. Gene mapping of Marfan syndrome is described, focusing on cloning and sequencing of the human fibrillin 15 gene. Research on fibrillin gene markers in human diseases is highlighted. Future directions for genetic research on single-gene disorders of collagen are suggested. 110 references and 19 figures.

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Conditions of Developmental Disturbances Source: in Marx, R.E.; Stern, D. Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Chicago, IL: Quintessence Publishing Co, Inc. 2003. p.207-254. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $ 399.00 plus shipping and handling. ISBN: 0867153903. Summary: This chapter on conditions of developmental disturbances is from a clinically oriented guide for oral and maxillofacial surgeons and other advanced dental and medical specialists who deal with pathologies in the oral cavity, midface, and neck. Topics include persistent lingual thyroid gland, osteoporotic bone marrow defects, lingual salivary gland depressions, idiopathic bone cavities, white sponge nevus, hereditary benign intraepithelial dyskeratosis, Darier disease, psoriasis, focal epithelial hyperplasia (Heck disease), hereditary gingival fibromatosis, hereditary hemorrhagic telangiectasia, encephalotrigeminal angiomatosis, cleidocranial dysplasia, osteogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasia, amelogenesis imperfecta, hemifacial hyperplasia, hemifacial atrophy (Romberg syndrome), Ehlers-Danlos syndrome, Marfan syndrome, mandibulofacial dysostosis (Treacher Collins syndrome), hemifacial microsomia oculoauriculovertebral dysplasia, Beckwith-Wiedemann syndrome, epidermolysis bullosa, and ectodermal dysplasia. For each condition, the authors discuss clinical presentation and pathogenesis, differential diagnosis, diagnostic

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work-up, histopathology, treatment, and prognosis. Full-color photographs and blackand-white radiographs illustrate the chapter. 56 figures. •

Congenital and Hereditable Disorders with Lesser Orofacial Involvement Source: in Scully, C., et al. Color Atlas of Orofacial Health and Disease in Children and Adolescents. London, England: Martin Dunitz Ltd. 2002. p.43-70. Contact: Available from Martin Dunitz Ltd, The Livery House. 7-9 Pratt Street, London, England NW1 0AE. 4404074822202. Website: www.dunitz.co.uk. Email: [email protected]. PRICE: $125.00 plus shipping and handling. ISBN: 1841841021. Summary: This chapter on congenital (present at birth) and hereditable disorders with lesser orofacial involvement is from a full-color atlas that covers the presentation of the common orofacial disorders and a wide range of less common and some rare disorders. Topics include Apert's syndrome, condroectodermal dysplasia (Ellis-Van Creveld syndrome), cleidocranial dysplasia or dysostosis, Coffin-Lowry syndrome, Cowden's syndrome, Crouzon's syndrome (craniofacial dysostosis), dyskeratosis congenital, ectodermal dysplasia, Ehlers-Danlos syndrome, epidermolysis bullosa, epiloia (tuberous sclerosis), fragile X syndrome, Gardner's syndrome, Goldenhar's syndrome, Gorlin's syndrome, incontinentia pigmenti, Kabuki make-up syndrome, mucopolysaccharidoses, Morquio's syndrome, multiple endocrine neoplasia syndrome, Noonan's syndrome, osteogenesis imperfecta, Peutz-Jeghers syndrome, Prader-Willi syndrome, RubensteinTaybi syndrome, Sjogren-Larsson syndrome, Sotos syndrome (cerebral giantism), trichorhinopharyngeal syndrome type 1, Von Recklinhausen neurofibromatosis, and Williams syndrome. Full-color photographs are accompanied by brief text entries describing each condition and noting diagnostic and management considerations for each. 72 figures.

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Metabolic and Genetic Jaw Diseases Source: in Regezi, J.A. and Sciubba, J.J. Oral Pathology: Clinical Pathologic Correlations. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 417-452. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32821-9854. (800) 545-2522. Fax (800) 874-6418. Website: www.wbsaunders.com. PRICE: $63.95. ISBN: 0721677312. Summary: This chapter on metabolic and genetic jaw diseases is from a pathology textbook that presents current concepts of oral and maxillofacial pathology in order to enhance the reader's diagnostic skills through the use of differential diagnosis strategies. The text offers readers detailed guidance of etiology, pathogenesis, clinical features, histopathology, differential diagnosis, and treatment of oral diseases of the mucosa, submucosa, and bone. This chapter covers metabolic conditions, including Paget's disease, hyperparathyroidism, hyperthyroidism, hypophosphatasia, infantile cortical hyperostosis, phantom bone disease, and acromegaly; and genetic abnormalities, including cherubism, osteopetrosis, osteogenesis imperfecta, cleidocranial dysplasia, Crouzon's syndrome (craniofacial dysostosis), Treacher Collins syndrome (mandibulofacial dysostosis), Pierre Robin syndrome, Marfan's syndrome, Ehlers Danlos syndrome, Down syndrome (trisomy 21), hemifacial atrophy, hemifacial hypertrophy, clefts of the lip and palate, and Fragile X syndrome. 32 figures. 142 references.

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Musculoskeletal Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 310-335. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: This chapter on musculoskeletal disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. The authors note that the jaws and temporomandibular joints are part of the skeletal system, but are rarely involved by systemic disease and few skeletal diseases affect the management of the dental patient directly. Muscle disorders are relatively uncommon and involvement of the masticatory (chewing) and facial muscles is not necessarily a prominent feature. However, for patients with musculoskeletal disease, access to the dental clinic or getting into or out of the chair may be difficult. Topics include genetic skeletal diseases, osteogenesis imperfecta, achondroplasia, cleidocranial dysplasia, osteopetrosis (Albers Schonberg disease), Marfan's syndrome, Ehlers Danlos syndrome, diseases of calcium metabolism and bone, rickets and osteomalacia, osteoporosis, William's syndrome, tumoral calcinosis, fibrous dysplasia, Paget's disease of bone (osteitis deformans), osteoarthritis, rheumatoid arthritis, Felty's syndrome, juvenile rheumatoid arthritis (childhood polyarthritis), psoriatic arthritis, Lyme disease, gout, ankylosing spondylitis, Reiter's disease, prosthetic joint replacements, genetic myopathies, polymyositis and dermatomyositis, and cranial arteritis and polymyalgia rhematica. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 4 figures. 10 tables. 61 references.

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Special Considerations for Children with Fluctuating-Progressive Hearing Loss Source: in Bess, F.H.; Gravel, J.S.; Tharpe, A.M., eds. Amplification for Children with Auditory Deficits. Nashville, TN: Bill Wilkerson Center Press. 1996. p. 339-365. Contact: Available from Bill Wilkerson Center Press. 1114 19th Avenue South, Nashville, TN 37212-2197. (615) 936-5023. Fax (615) 936-5013. PRICE: $55.00 plus shipping and handling. ISBN: 096314393X. Summary: This chapter, from a textbook on amplification for children with auditory deficits, discusses special considerations for children with fluctuating or progressive hearing loss. One consideration, particularly for younger children, is that audiologists may assume that changes in audiometric results reflect attention or nonsensory factors, as opposed to true changes in hearing sensitivity. The author attempts to raise the reader's level of suspicion for fluctuating or progressive hearing loss in children by reviewing several causes and patterns of such changes. The causes discussed include genetic hearing loss without associated abnormalities, including autosomal dominant progressive SNHL, x-linked progressive hearing loss, and otosclerosis; genetic hearing loss with associated abnormalities, including Albers-Schonberg disease, Alport's syndrome, branchio-oto-renal (BOR) syndrome, CHARGE syndrome, mucopolysaccharidosis syndrome (MPS), neurofibromatosis, osteogenesis imperfecta, retinitis pigmentosa, Stickler syndrome, and Waardenburg's syndrome; acquired hearing loss, including prenatal causes such as infections or inner ear malformations, perinatal causes such as hyperbilirubinemia and persistent pulmonary hypertension of the newborn, and postnatal causes, such as autoimmune inner ear disease, Meniere's disease, meningitis, otitis media, and perilymphatic fistula. The author makes

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recommendations for the audiologic management of children with fluctuating or progressive hearing loss. The chapter concludes with the presentation of three relevant case reports. 4 figures. 124 references. •

Physical Disability and Sensory Impairment Source: in Griffiths, J. and Boyle, S. Colour Guide to Holistic Oral Care: A Practical Approach. Mosby-Year Book Europe. 1993. p. 131-150. Contact: Available from Mosby-Year Book Europe. Lynton House, 7-12 Tavistock Square, London WC1H 9LB, England. Telephone 0171-391 4471. Fax 0171-391 6598. ISBN: 0723417792. Summary: This chapter, from a textbook that outlines the role of the nurse in oral health care, discusses the oral care of people with physical disability or sensory impairment. The authors summarize the more common conditions that may affect manual dexterity, arm control, and mobility. Topics covered include the prevalence of physical disability; barriers to oral health; arthritis; brittle bone disease (osteogenesis imperfecta); rickets and osteomalacia; osteoporosis; Paget's disease (oteitis deformans); muscular dystrophies and myotonic disorders; myasthenia gravis; motor neurone disease; multiple sclerosis; Guillain-Barre syndrome; stroke (cerebrovascular accident); Bell's palsy; Parkinson's disease; cleft lip and palate; cerebral palsy; spina bifida and hydrocephalus; spinal injuries and trauma; head injury; epilepsy; and sensory impairment. 6 tables. 22 references. (AA-M).

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CHAPTER 8. MULTIMEDIA ON OSTEOGENESIS IMPERFECTA Overview In this chapter, we show you how to keep current on multimedia sources of information on osteogenesis imperfecta. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on osteogenesis imperfecta is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “osteogenesis imperfecta” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “osteogenesis imperfecta” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on osteogenesis imperfecta: •

Plan for Success: An Educator's Guide to Students with Osteogenesis Imperfecta (OI) Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1998. (videocassette and teaching guide). Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: 5.00 plus shipping and handling. Summary: This videotape and guide for educators helps them work with parents of children with osteogenesis imperfecta (OI) in developing an individualized educational plan for their child. The video guides educators and parents through the planning steps that will help children with OI to fully participate in all school activities. It includes a discussion of education issues by two students with OI, their parents, teachers, and various school personnel. Topics range from adaptive physical education to planning for life after graduation. The video is accompanied by a guide that provides information on

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applicable education laws and requirements, including the Individuals with Disabilities Education Act and Section 504 of the Rehabilitation Act of 1973. It addresses issues related to including children with OI in all school activities: overcoming architectural barriers, making mobility accommodations, using assistive devices or personal aides, developing an appropriate fire evacuation plan, providing accessible transportation, offering physical or occupational therapy, adapting physical education activity and playground equipment, accommodating for hearing loss, and handling absences for surgery or injury. Other topics include dealing with a fracture that occurs at school and helping a student's peers better understand OI. The guide also includes a list of national, State, and print and video resources. •

Going Places: A Day in the Life of a Teenager with Osteogenesis Imperfecta (OI) Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1998. (videocassette and teaching guide). Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: 5.00 plus shipping and handling. Summary: This videotape for pre-adolescents and adolescents with osteogenesis imperfecta (OI), or people who know someone with OI follows a ninth-grade student with OI through a day of classes, extracurricular activities, shopping, and time with her family. She comments on the role that OI plays in her life, including accommodations that help her fully participate in school, friendships, plans for an independent future, and some of the ways OI affects her daily routine. The student advises others with OI to do whatever they are capable of doing and asks that other students be conscientious about including their peers with OI in all of their activities. An accompanying study guide provides information about living with OI, offers tips for friends and classmates, and includes questions for discussion.

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CHAPTER 9. PERIODICALS AND NEWS ON OSTEOGENESIS IMPERFECTA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover osteogenesis imperfecta.

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

Gene targeting disrupts osteogenesis imperfecta mutation in stem cells Source: Reuters Medical News Date: February 20, 2004

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Pamidronate does not harm linear growth in children with osteogenesis imperfecta Source: Reuters Industry Breifing Date: May 26, 2003

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Bisphosphonates provide long-term benefit in osteogenesis imperfecta Source: Reuters Industry Breifing Date: May 06, 2002

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Increased paternal age linked to osteogenesis imperfecta in offspring Source: Reuters Medical News Date: May 22, 2001

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Bisphosphonate therapy promising for severe osteogenesis imperfecta Source: Reuters Medical News Date: October 05, 1998 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 “osteogenesis imperfecta” (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 “osteogenesis imperfecta” (or synonyms). If you know the name of a company that is relevant to osteogenesis imperfecta, you can go to any stock trading Web site (such as

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http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “osteogenesis imperfecta” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “osteogenesis imperfecta” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on osteogenesis imperfecta: •

Spotlight on: Current Progress in Finding Genes Involved in Hearing Impairment Source: Advances in the Genetics of Deafness. 1(2): 1-4. Spring 1995. Contact: Available from Boys Town National Research Hospital (BTNRH). 555 North 30th Street, Omaha, NE 68131. (800) 320-1171. Summary: This article discusses recent progress in research investigating the genes involved in hearing impairment. The author notes that despite rather daunting obstacles, research into the different types of genetic hearing impairment has progressed significantly. Several genes have been localized to specific chromosomes and in some cases, the actual gene responsible has been identified, cloned, and its function determined. Types of hearing impairment discussed include that associated with Usher syndrome; Waardenburg syndrome; Alport syndrome; branchio-oto-renal syndrome; Stickler syndrome; osteogenesis imperfecta; Crouzon syndrome; Treacher-Collins syndrome; Norries syndrome; X-linked hearing impairment; neurofibromatosis II (NF2); and non-syndromic hearing impairment. The author concludes with a brief discussion of the present and future impact of information coming from genetic research in this area. 1 table. 24 references.

Academic Periodicals covering Osteogenesis Imperfecta Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to osteogenesis imperfecta. In addition to these sources, you can search for articles covering osteogenesis imperfecta 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.”

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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. 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 osteogenesis imperfecta. 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 osteogenesis imperfecta. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks,

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etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to osteogenesis imperfecta: Growth Hormone •

Systemic - U.S. Brands: Genotropin; Genotropin Miniquick; Humatrope; Norditropin; Nutropin; Nutropin AQ; Protropin; Saizen; Serostim http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202269.html

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

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

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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

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

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

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

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

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

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

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

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

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

11

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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

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

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

•

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

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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/

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

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

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

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

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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

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

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

12

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

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

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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 “osteogenesis imperfecta” (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 3140 36 22 2 60 3260

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

14

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

15

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

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

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

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

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

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

•

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

The Genome Project and Osteogenesis Imperfecta In the following section, we will discuss databases and references which relate to the Genome Project and osteogenesis imperfecta. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 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. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “osteogenesis imperfecta” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for osteogenesis imperfecta: •

Osteogenesis Imperfecta Congenita Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=166210

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Osteogenesis Imperfecta Congenita, Microcephaly, and Cataracts Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=259410

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Osteogenesis Imperfecta with Opalescent Teeth Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=166240

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Osteogenesis Imperfecta with Opalescent Teeth, Blue Sclerae and Wormian Bones, but without Fractures Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=166230

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Osteogenesis Imperfecta with Unusual Skeletal Lesions Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=166260

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Osteogenesis Imperfecta, Progressively Deforming, with Normal Sclerae Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=259420

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Osteogenesis Imperfecta, Sillence Type Ii/iii, without Abnormality of Type I Collagen Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=259440

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Osteogenesis Imperfecta, Type I Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=166200

•

Osteogenesis Imperfecta, Type Iv Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=166220 Genes and Disease (NCBI - Map)

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

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

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge

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syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html •

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

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

•

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

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

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

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

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

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

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

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

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

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•

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

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

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

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

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

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

•

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

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “osteogenesis imperfecta” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human 23

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “osteogenesis imperfecta” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on osteogenesis imperfecta 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 osteogenesis imperfecta. 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 osteogenesis imperfecta. 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 “osteogenesis imperfecta”:

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Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Child Abuse http://www.nlm.nih.gov/medlineplus/childabuse.html Dwarfism http://www.nlm.nih.gov/medlineplus/dwarfism.html Genetic Testing/Counseling http://www.nlm.nih.gov/medlineplus/genetictestingcounseling.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Paget's Disease of Bone http://www.nlm.nih.gov/medlineplus/pagetsdiseaseofbone.html Phenylketonuria http://www.nlm.nih.gov/medlineplus/phenylketonuria.html

Within the health topic page dedicated to osteogenesis imperfecta, the following was listed: •

General/Overviews Osteogenesis Imperfecta Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=308&topcategory=Abou t%2520Orthopaedics&all=all

•

Diagnosis/Symptoms Bone Densitometry in Children and Adults with OI Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=i118i&doctype=HTML%2BFact%2BSheet& doctitle=Bone%2BDensitometry%2Bin%2BChildren%2Band%2BAdults%2Bwith%2 BOsteogenesis%2BImperfecta

•

Treatment Osteogenesis Imperfecta Issues: Rodding Surgery Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=Rodding Use of Bisphosphonates in Metabolic Bone Diseases Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=p128i&doctitle=Use%2Bof%2BBisphospho nates%2Bin%2BMetabolic%2BBone%2BDiseases&doctype=HTML%2BFact%2BShee t

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Nutrition Osteogenesis Imperfecta Issues: Nutrition Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=Nutrition

•

Coping Osteogenesis Imperfecta Issues: Psychosocial Needs of the Family Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=PsychNeeds

•

Specific Conditions/Aspects Broken Bones Source: Nemours Foundation http://kidshealth.org/parent/general/aches/broken_bones.html Hearing Loss and Bone Disorders Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r604i&doctitle=Hearing%2BLoss%2B%252 6%2BBone%2BDisorders&doctype=HTML%2BFact%2BSheet Novel Forms of Osteogenesis Imperfecta: Types V & VI Source: Osteogenesis Imperfecta Foundation http://oif.convio.com/site/PageServer?pagename=NovelForms Osteogenesis Imperfecta Issues: Fracture Management Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=FractMgmt Osteogenesis Imperfecta Issues: Surgical Considerations Source: Osteogenesis Imperfecta Foundation http://oif.convio.com/site/PageServer?pagename=SurgConsid Understanding Type I OI Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=TypeI What People with Osteogenesis Imperfecta Need to Know about Osteoporosis Source: Osteogenesis Imperfecta Foundation http://oif.convio.com/site/PageServer?pagename=OIandOsteo

•

Children Caring for Infants and Children with Osteogenesis Imperfecta Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=InfChild Planning for Post Operative Care for Children with OI Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=PostOpChildren

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•


From the National Institutes of Health Fast Facts on Osteogenesis Imperfecta Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=i101i&doctype=HTML%2BFact%2BSheet& doctitle=Fast%2BFacts%2Bon%2BOsteogenesis%2BImperfecta Osteogenesis Imperfecta Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/oi.html Questions and Answers about Heritable Disorders of Connective Tissue Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/connective/connective.htm

•

Organizations National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ National Institutes of Health Osteoporosis and Related Bone Diseases~National Resource Center Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.osteo.org Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer

•

Women Osteogenesis Imperfecta Issues: Obstetric Considerations for Women without OI Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=PregNonAffected Osteogenesis Imperfecta Issues: Pregnancy Considerations for Women with OI Source: Osteogenesis Imperfecta Foundation http://www.oif.org/site/PageServer?pagename=PregOI

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 Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on osteogenesis imperfecta. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search

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options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Osteogenesis Imperfecta Source: Atlanta, GA: Arthritis Foundation. 1997. 2 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. http://www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call 800-283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This fact sheet for people with osteogenesis imperfecta (OI) presents an overview of this group of inherited disorders. It explains how OI results from an alteration in either the chemical makeup or production of collagen, and that the most common feature of OI is brittle bones that break easily. The fact sheet describes the types of OI and their symptoms, and it discusses ways to reduce the severity of symptoms. The fact sheet also addresses special considerations applying to children with OI, highlights research efforts, and provides information on the Arthritis Foundation.

•

Fast Facts on Osteogenesis Imperfecta Source: Osteogenesis Imperfecta Foundation. 1999. 3 p. Contact: Available online from Osteogenesis Imperfecta Foundation. Website: www.oif.org. Summary: This fact sheet provides information to patients on osteogenesis imperfecta (OI), a genetic disorder marked by abnormal fragility of the bones due to a genetic defect that affects the body's ability to produce collagen. As many as 50,000 people in the US may be affected by OI. Diagnosis may be based on clinical features and confirmed by collagen and DNA testing. The clinical features of types I, II, III, and IV OI are listed. Treatment for OI focuses on preventing fractures and controlling other symptoms. Mobility aids are used for patients with severe OI. Rodding surgery, used to strengthen and prevent deformity in the long bones, is frequently used. Patients with OI should exercise when possible and maintain a healthy weight. Patients should avoid smoking, alcohol, caffeine, and steroids.

•

Caring for Infants and Children With Osteogenesis Imperfecta Source: Osteogenesis Imperfecta Foundation. February 2002. 11 p. Contact: Available online from Osteogenesis Imperfecta Foundation. Website: www.oif.org. Summary: This fact sheet provides parents of children with osteogenesis imperfecta (OI) with guidelines on caring for their child. Most forms of OI are caused by imperfectly formed bone collagen that results from a genetic defect. Symptoms vary according to the form of OI. The severity of symptoms varies between individuals. The fact sheet outlines the common features of the disease. It also addresses issues that parents need to consider after learning that their child has OI. Topics include choosing and using car seats and strollers, handling, selecting clothing, bathing, recognizing and handling fractures, caring for a cast, teaching a child with OI to be independent, helping him or her achieve maximum mobility by using mobility aids, encouraging physical therapy, using braces, walking, managing symptoms, receiving special educational

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services, and integrating a child with OI into a regular classroom. The fact sheet also addresses the importance of keeping a precise record of the child's X-rays and the importance of dental care. A list of additional resources and readings is appended. •

What People With Osteogenesis Imperfecta Need to Know About Osteoporosis Source: Osteogenesis Imperfecta Foundation. 2003. 2 p. Contact: Available online from Osteogenesis Imperfecta Foundation. Website: www.oif.org. Summary: This fact sheet provides patients with osteogenesis imprefecta (OI) with information for preventing osteoporosis. Osteoporosis is a disease in which bone mass decreases causing the risk of fracture to increase. Patients should eat a diet containing proper amounts of calcium and vitamin D for their body size; perform weight bearing exercises including walking, dancing, and swimming after consulting with their doctor or a physical therapist; and avoid smoking or consuming alcoholic beverages. Because patients with OI may have a lower bone mineral density (BMD) when compared to peak bone measurements of young adults, they should have their bone mineral density measured in early middle age in order to provide a standard in which to measure any later changes in bone density. Patients should consult their doctor about using medications that can help prevent bone loss and increase bone mass.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “osteogenesis imperfecta” (or synonyms). The following was recently posted: •

American Gastroenterological Association medical position statement: celiac sprue Source: American Gastroenterological Association - Medical Specialty Society; 2000 November 12 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3058&nbr=2284&a mp;string=brittle+AND+bone+AND+disease

•

Clinical practice guideline (second edition) for the diagnosis, treatment, and management of reflex sympathetic dystrophy/complex regional pain syndrome (RSD/CRPS) Source: Reflex Sympathetic Dystrophy Syndrome Association - Private Nonprofit Organization; 2002 February; 46 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3204&nbr=2430&a mp;string=brittle+AND+bone+AND+disease

Patient Resources

•

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Diagnosis and treatment of autoimmune hepatitis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2002 August; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3447&nbr=2673&a mp;string=brittle+AND+bone+AND+disease

•

Global initiative for asthma. Global strategy for asthma management and prevention Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1995 January (revised 2002); 176 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3203&nbr=2429&a mp;string=brittle+AND+bone+AND+disease

•

Osteoporosis. Guide to prevention, diagnosis, and treatment Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 1999 (revised 2001); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3430&nbr=2656&a mp;string=osteogenesis+AND+imperfecta

•

Physical activity in the prevention, treatment and rehabilitation of diseases Source: Finnish Medical Society Duodecim - Professional Association; 2002 May 7; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3398&nbr=2624&a mp;string=brittle+AND+bone+AND+disease

•

Reflex sympathetic dystrophy/complex regional pain syndrome clinical practice guidelines - third edition Source: International Research Foundation for RSD/CRPS - Private Nonprofit Research Organization; 2003 January 1; 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4117&nbr=3162&a mp;string=brittle+AND+bone+AND+disease Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

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•


OI (Osteogenesis Imperfecta) Issues: Caring for Children and Infants Summary: Osteogenesis imperfecta (OI) can literally be translated as imperfectly formed bones. Most forms of OI are caused by imperfectly formed bone collagen that results from a genetic defect. Source: Osteogenesis Imperfecta Foundation, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7010

•

OI Issues: Genetics Summary: Osteogenesis imperfecta (OI) is the result of a mutation in one of the two genes that carry instructions for making type 1 collagen (the major protein in bone and skin). Source: Osteogenesis Imperfecta Foundation, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7012

•

Osteogenesis Imperfecta: Fast Facts Summary: This online consumer health document offers a definition of this genetic disorder, as well as prevalence, diagnosis, clinical features, and treatment information. Source: Osteogenesis Imperfecta Foundation, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2230 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 osteogenesis imperfecta. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

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

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

Patient Resources

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

•

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

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Associations and Osteogenesis Imperfecta The following is a list of associations that provide information on and resources relating to osteogenesis imperfecta: •

Canadian Osteogenesis Imperfecta Society Telephone: 519-436-0025 Fax: 519-351-4043 Email: [email protected] Web Site: http://www.oif.org Background: The Canadian Osteogenesis Imperfecta Society (COIS) is an international, nonprofit, charitable organization dedicated to assisting individuals affected by Osteogenesis Imperfecta (OI). Osteogenesis Imperfecta is a genetic disorder characterized by abnormally fragile, brittle bones. Established in 1983, the Society aims to provide emotional support on a personal level for parents and people with Osteogenesis Imperfecta; encourage and foster Canadian medical research into the underlying causes of OI; acquaint medical personnel, hospitals, educational institutions, and social agencies with all facets of Osteogenesis Imperfecta; maintain and up-to-date library of literature both medical and general pertaining to OI; promote and understand awareness of brittle bones by the public; and solicit and receive funds to carry out the aims of the Canadian Osteogenesis Imperfecta Society. Relevant area(s) of interest: Brittle Bone Disease, Lobstein Disease Type I, Osteogenesis Imperfecta, Osteopathyrosis, Vrolik Disease Type II

•

Osteogenesis Imperfecta Foundation, Inc Telephone: (301) 947-0083 Toll-free: (800) 981-2663 Fax: (301) 947-0456 Email: [email protected] Web Site: http://www.oif.org Background: The Osteogenesis Imperfecta Foundation, Inc. is a nonprofit organization dedicated to improving the quality of life for individuals affected by osteogenesis imperfecta through research, education, awareness, and mutual support. Osteogenesis imperfecta (OI) is a genetic disorder characterized by abnormally fragile bones. Established in 1970, the Foundation offers information and support to affected individuals, family members, and health professionals. The Foundation also funds and encourages research into the causes of and treatments for OI. In addition, the Foundation provides numerous print, video, and online resources, facilitates peer contact, fosters local support groups, holds biannual conferences, engages in patient advocacy, and provides physician referrals. Relevant area(s) of interest: Osteogenesis Imperfecta

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to osteogenesis imperfecta. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with osteogenesis imperfecta. 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 osteogenesis imperfecta. 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 “osteogenesis imperfecta” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “osteogenesis imperfecta”. 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 “osteogenesis imperfecta” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “osteogenesis imperfecta” (or a synonym) into the search box, and click “Submit Query.”

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.25

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

25

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)26: •

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

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

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

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

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

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

•

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

26

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

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•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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/

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

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

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

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

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

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

•

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

•

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

•

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

•

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

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

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

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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/

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

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

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

•

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

•

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

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

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Osteogenesis Imperfecta Osteogenesis imperfecta Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001573.htm

•

Signs & Symptoms for Osteogenesis Imperfecta Bruising Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Deafness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Hearing loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Low nasal bridge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003056.htm

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Pectus carinatum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003321.htm Pectus excavatum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003320.htm Short stature Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003271.htm •

Diagnostics and Tests for Osteogenesis Imperfecta Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Bone X-rays Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003808.htm Punch biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

•

Surgery and Procedures for Osteogenesis Imperfecta Bone marrow transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003009.htm

•

Background Topics for Osteogenesis Imperfecta Bone fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Broken bone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Fractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm

Online Glossaries 145

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

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

•

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

•

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

•

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

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OSTEOGENESIS IMPERFECTA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] 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] 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] 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] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] 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] 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] Airway: A device for securing unobstructed passage of air into and out of the lungs during

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general anesthesia. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [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] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] 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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amelogenesis Imperfecta: Either hereditary enamel hypoplasia or hypocalcification. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH]

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Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] 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 and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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

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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] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [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] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteritis: Inflammation of an artery. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and

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necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] 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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Audiometry: The testing of the acuity of the sense of hearing to determine the thresholds of the lowest intensity levels at which an individual can hear a set of tones. The frequencies between 125 and 8000 Hz are used to test air conduction thresholds, and the frequencies between 250 and 4000 Hz are used to test bone conduction thresholds. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU]

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Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] 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] 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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to

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bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Conduction: Sound transmission through the bones of the skull to the inner ear. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH]

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Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [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] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [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] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [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 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)

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and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [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] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord.

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Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] 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] Chondrodysplasia Punctata: A heterogeneous group of bone dysplasias, the common character of which is stippling of the epiphyses in infancy. The group includes a severe autosomal recessive form (Chondrodysplasia punctata, rhizomelic), an autosomal dominant form (Conradi-Hunermann syndrome), and a milder X-linked form. Metabolic defects associated with impaired peroxisomes are present only in the rhizomelic form. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] 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] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH]

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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the

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classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH]

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Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [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 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be

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classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [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] 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] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystostomy: Surgical creation of an opening (stoma) for drainage of the urinary bladder. [NIH]

Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] 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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids

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produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental implant: A small metal pin placed inside the jawbone to mimic the root of a tooth. Dental implants can be used to help anchor a false tooth or teeth, or a crown or bridge. [NIH] Dentin Dysplasia: Abnormal tissue development or growth occurring subsequent to the appearance of the primordial cells. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexterity: Ability to move the hands easily and skillfully. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] 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] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disability Evaluation: Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for Social Security and workmen's compensation benefits. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] 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

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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] Disulphide: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]

Dyskeratosis Congenita: A disturbance in normal keratinization, resulting, in the eye, in hornification of the epithelial layer of the cornea or conjunctiva. [NIH] Dysostosis: Defective bone formation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eardrum: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus

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becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [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] 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] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH]

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Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epiphyses: The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] 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] 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] Expander: Any of several colloidal substances of high molecular weight. used as a blood or

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plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [NIH] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [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] Febrile: Pertaining to or characterized by fever. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [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] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is

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a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroma: A benign tumor of fibrous or fully developed connective tissue. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes bony callus formation and normal replacement of bone tissue. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] 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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be

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detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [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] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH]

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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] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [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] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts

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may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [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] Hemoglobinuria: The presence of free hemoglobin in the urine. [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]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: 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]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

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Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] 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] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperostosis: Increase in the mass of bone per unit volume. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH]

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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] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] 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] Illusion: A false interpretation of a genuine percept. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] 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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH]

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Incontinentia Pigmenti: A genodermatosis occurring mostly in females and characterized by skin changes in three phases - vesiculobullous, verrucous papillomatous, and macular melanodermic. Hyperpigmentation is bizarre and irregular. Sixty percent of patients have abnormalities of eyes, teeth, central nervous system, and skin appendages. [NIH] Incus: One of three ossicles of the middle ear. It conducts sound vibrations from the malleus to the stapes. [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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important

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processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] 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] Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest

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DNA fragments are up to 50 kilobases long. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Kink: Deviation from the normal long axis, as in a fractured bone healed out of line. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Labyrinthitis: Inflammation of the inner ear. [NIH] Lacrimal: Pertaining to the tears. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] 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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH]

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Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] 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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH]

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Malleus: The largest of the auditory ossicles, and the one attached to the membrana tympani (tympanic membrane). Its club-shaped head articulates with the incus. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mandibulofacial Dysostosis: A rare congenital anomaly characterized by antimongoloid oblique palpebral fissures, coloboma of the lower eyelids, hypoplasia of the facial bones, malformations of the external ears and sometimes middle and inner ears, an abnormally large mouth. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and

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lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microradiography: Production of a radiographic image of a small or very thin object on fine-grained photographic film under conditions which permit subsequent microscopic examination or enlargement of the radiograph at linear magnifications of up to several hundred and with a resolution approaching the resolving power of the photographic emulsion (about 1000 lines per millimeter). [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH]

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Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] 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] 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] Morphological: Relating to the configuration or the structure of live organs. [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Mucopolysaccharidoses: Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]

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Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] 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] Neurologic: Having to do with nerves or the nervous system. [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

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system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [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] 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 Family: A family composed of spouses and their children. [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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [NIH]

Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic cup: The white, cup-like area in the center of the optic disc. [NIH]

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Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Orthopedics: A surgical specialty which utilizes medical, surgical, and physical methods to treat and correct deformities, diseases, and injuries to the skeletal system, its articulations, and associated structures. [NIH] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteitis Fibrosa Cystica: A fibrous degeneration, cyst formation, and the presence of fibrous nodules in bone, usually due to hyperparathyroidism. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteochondrodysplasias: Abnormal development of cartilage and bone. [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] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes

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via protoplasmic projections called canaliculi. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [NIH] Otorrhea: A discharge from the ear, especially a purulent one. [EU] Otosclerosis: The formation of spongy bone in the labyrinth capsule. The ossicles can become fixed and unable to transmit sound vibrations, thereby causing deafness. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or

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concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Patella: The flat, triangular bone situated at the anterior part of the knee. [NIH] Paternal Age: Age of the father. [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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pedicle: Embryonic link between the optic vesicle or optic cup and the forebrain or diencephalon, which becomes the optic nerve. [NIH]

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Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Pericytes: Smooth muscle cell that wraps around normal blood vessels. [NIH] Perilymph: The fluid contained within the space separating the membranous from the osseous labyrinth of the ear. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Personnel, Hospital: The individuals employed by the hospital. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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.

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[NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] 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] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for

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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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Progeny: The offspring produced in any generation. [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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein 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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It

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begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]

Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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]

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Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation 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] Radicular: Having the character of or relating to a radicle or root. [NIH] Radicular Cyst: Slow-growing fluid-filled epithelial sac at the apex of a tooth with a nonvital pulp or defective root canal filling. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] 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] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the

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cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Reoperation: A repeat operation for the same condition in the same patient. It includes reoperation for reexamination, reoperation for disease progression or recurrence, or reoperation following operative failure. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Research Support: Financial support of research activities. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH]

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Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [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] 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] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [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]

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Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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]

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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH]

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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] Skin Abnormalities: Congenital structural abnormalities of the skin. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of

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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] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Injuries: Injuries involving the vertebral column. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Spontaneous Fractures: Fracture in the course of a normal movement of a bone weakened by disease. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Stabilization: The creation of a stable state. [EU] Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

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] Stippling: A dotted appearance in cells on staining. [NIH] Stoma: A surgically created opening from an area inside the body to the outside. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]

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Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Subtrochanteric: Below a trochanter. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Synchrotron: An accelerator in which the particles are guided by an increasing magnetic field while they are accelerated several times in an approximately circular path by electric fields produced by a high-frequency generator. [NIH] Syncytium: A living nucleated tissue without apparent cellular structure; a tissue composed of a mass of nucleated protoplasm without cell boundaries. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] 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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thanatophoric Dysplasia: A severe form of neonatal dwarfism with very short limbs. All cases have died at birth or in the neonatal period. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU]

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Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [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] 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] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tibiae: The long bone on the medial and pre-axial border of the leg. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Expansion: Process whereby tissue adjacent to a soft tissue defect is expanded by means of a subcutaneously implanted reservoir. The procedure is used in reconstructive surgery for injuries caused by trauma, burns, or ablative surgery. [NIH] 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] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of

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toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [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]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Uterine Rupture: A tearing of uterine tissue; it may be traumatic or spontaneous due to

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multiple pregnancy, large fetus, previous scarring, or obstruction. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Venous: Of or pertaining to the veins. [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 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] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH]

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Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [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] Volition: Voluntary activity without external compulsion. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX 3 3-dimensional, 19, 147, 186 A Abdomen, 147, 153, 174, 183, 193, 195, 198 Acoustic, 100, 147, 197 Actin, 147, 179 Acuity, 147, 151 Adaptation, 22, 147, 180 Adenosine, 147, 153, 184 Adjustment, 147 Adverse Effect, 6, 23, 147, 191 Aerobic, 98, 147 Afferent, 147, 165 Affinity, 9, 10, 147, 192 Age of Onset, 4, 147, 153 Airway, 147, 192 Alendronate, 5, 12, 28, 148 Alertness, 148, 153 Algorithms, 148, 152 Alkaline, 19, 148, 154 Alkaline Phosphatase, 19, 148 Alleles, 9, 23, 59, 148, 169 Allogeneic, 8, 25, 52, 77, 148 Allogeneic bone marrow transplantation, 8, 148 Allograft, 91, 148 Alpha Particles, 148, 188 Alternative medicine, 108, 148 Alternative Splicing, 58, 148, 187 Alveolar Bone Loss, 93, 148 Alveolar Process, 148, 189 Amelogenesis Imperfecta, 101, 148 Amino Acid Sequence, 21, 148, 149, 164, 167, 186 Amino Acid Substitution, 27, 148 Amino Acids, 9, 19, 21, 68, 148, 149, 167, 184, 185, 187 Amino-terminal, 149, 186 Amnion, 149 Amniotic Fluid, 66, 149 Amplification, 103, 149 Anaesthesia, 65, 149, 172 Anal, 149, 166 Analogous, 5, 149, 196 Anaphylatoxins, 149, 158 Anaplasia, 149 Anatomical, 13, 149, 151, 163, 171, 191 Anemia, 121, 149, 182

Anesthesia, 62, 65, 148, 149 Aneurysm, 67, 149 Animal model, 5, 6, 11, 149 Anorexia, 149, 182 Antagonism, 149, 153 Antibodies, 7, 17, 22, 149, 150, 164, 168, 171, 175, 185 Antibody, 147, 150, 157, 160, 168, 170, 171, 172, 176, 188, 192 Anticoagulant, 150, 186 Antigen, 147, 149, 150, 158, 164, 167, 170, 171, 172, 176 Antigen-Antibody Complex, 150, 158 Anti-inflammatory, 150, 167 Aorta, 8, 150, 197 Aortic Valve, 56, 63, 150 Aphakia, 150, 189 Aplasia, 150, 162 Apnea, 150 Apoptosis, 94, 150, 155 Aqueous, 150, 151, 160, 163, 174 Arginine, 54, 92, 149, 150 Arterial, 19, 27, 150, 155, 170, 187 Arteries, 19, 21, 150, 152, 159, 175, 177, 179, 187 Arterioles, 150, 152, 154 Arteritis, 103, 150 Articular, 150, 181 Ascorbic Acid, 150, 170 Aspartate, 28, 151 Assay, 7, 10, 151, 171 Ataxia, 121, 151, 170, 194 Atrial, 52, 151 Atrium, 151, 177, 197 Atrophy, 101, 102, 121, 151 Audiometry, 100, 151 Auditory, 100, 103, 151, 162, 176, 196 Autoimmune disease, 151, 178 Autoimmune Hepatitis, 131, 151 Autologous, 8, 9, 151 B Bacteria, 150, 151, 161, 163, 177, 193, 197 Bacterial Physiology, 147, 151 Bacterium, 9, 151 Basal Ganglia, 151, 153 Basal Ganglia Diseases, 151 Base, 11, 35, 151, 160, 161, 167, 173, 185, 194

Osteogenesis imperfecta

Basement Membrane, 152, 165 Benign, 101, 152, 153, 166, 168, 179, 180 Benign tumor, 152, 166 Bewilderment, 152, 158 Bifida, 152 Bilateral, 30, 32, 100, 152, 183, 190 Bilirubin, 152, 170 Binding Sites, 10, 21, 152 Biochemical, 18, 19, 24, 30, 33, 54, 73, 76, 77, 92, 148, 152, 181, 186 Biological therapy, 152, 168 Biopolymers, 16, 152 Biopsy, 144, 152, 184 Biosynthesis, 90, 94, 152, 174, 182, 191 Biotechnology, 24, 26, 108, 117, 119, 120, 121, 122, 152 Bladder, 152, 160, 171, 178, 186, 196 Blood Coagulation, 152, 154, 195 Blood pressure, 152, 154, 170, 178, 187, 192 Blood vessel, 19, 152, 153, 154, 156, 163, 173, 176, 184, 192, 193, 194, 195, 197 Blot, 24, 92, 152 Body Fluids, 152, 162, 192 Bone Cements, 152, 185 Bone Conduction, 151, 153 Bone Density, 23, 66, 83, 84, 85, 90, 93, 130, 153 Bone Development, 11, 98, 153 Bone Marrow, 6, 8, 13, 14, 17, 20, 25, 33, 39, 52, 64, 66, 77, 101, 153, 175, 176, 178, 179, 194 Bone Marrow Cells, 6, 153, 176, 178 Bone Marrow Transplantation, 33, 153 Bone Resorption, 12, 50, 85, 153 Bone scan, 67, 153 Bowel, 149, 153, 161 Bowel Movement, 153, 161 Brain Neoplasms, 153, 170, 194 Branch, 73, 141, 153, 160, 176, 182, 183, 192, 194 Breakdown, 85, 153, 161, 166, 180, 191 Burns, 153, 195 C Caffeine, 129, 153 Calcification, 19, 154 Calcinosis, 103, 154 Calcium, 27, 32, 38, 103, 130, 153, 154, 158, 164, 170, 177, 181, 182, 183 Calculi, 154, 168 Callus, 30, 39, 41, 48, 49, 57, 72, 154, 166 Capillary, 154, 155, 197 Capillary Fragility, 154, 155

200

Carbon Dioxide, 154, 166 Carboxy, 57, 154 Carboxy-terminal, 57, 154 Carcinogen, 92, 154 Carcinogenic, 154, 180, 186, 193 Cardiac, 7, 32, 72, 153, 154, 179, 193 Cardiovascular, 94, 98, 154 Cardiovascular disease, 94, 154 Carotene, 154, 189 Case report, 4, 23, 29, 31, 32, 39, 41, 49, 51, 58, 59, 64, 68, 77, 104, 154, 157 Case series, 154, 157 Caspase, 94, 155 Cataract, 150, 155, 189 Catechin, 77, 155 Cause of Death, 68, 155 Cell, 7, 10, 12, 13, 17, 19, 20, 22, 25, 50, 52, 59, 72, 77, 90, 92, 94, 100, 120, 121, 147, 149, 150, 151, 152, 155, 156, 158, 160, 163, 165, 166, 167, 168, 169, 172, 173, 177, 178, 179, 180, 181, 182, 184, 185, 188, 189, 191, 194, 195, 196, 198 Cell Adhesion, 155, 172 Cell Death, 150, 155, 167, 179 Cell Division, 120, 151, 155, 160, 168, 177, 185, 191 Cell Lineage, 13, 155 Cell proliferation, 10, 72, 155 Cell Survival, 155, 168 Cell Transplantation, 13, 77, 155 Central Nervous System, 13, 27, 153, 155, 168, 170, 172, 178, 181, 185 Central Nervous System Infections, 155, 168, 170 Cerebellar, 151, 155, 189 Cerebral, 23, 27, 102, 104, 151, 153, 155, 156, 163, 165, 170, 187, 188 Cerebral Infarction, 155, 170 Cerebral Palsy, 23, 104, 155 Cerebrospinal, 100, 155, 170 Cerebrospinal fluid, 100, 155, 170 Cerebrovascular, 104, 151, 154, 156, 194 Cerebrum, 155, 156, 196 Cervical, 64, 68, 156 Cervix, 156 Character, 156, 160, 188 Chemotactic Factors, 156, 158 Cherubism, 102, 156 Cholesterol, 94, 156, 159, 174, 175, 191, 193 Chondrodysplasia Punctata, 26, 156 Chorioretinitis, 156, 190 Choroid, 156, 189, 190

201

Chromatin, 150, 156 Chromosomal, 10, 149, 156, 178, 190 Chromosome, 92, 156, 173, 174, 190, 191, 196 Chronic, 18, 93, 120, 156, 157, 161, 163, 172, 173, 185, 187, 194 Chronic Disease, 156, 157 Chronic renal, 156, 185 CIS, 156, 189 Cleave, 24, 156 Clinical Medicine, 49, 157, 186 Clinical study, 4, 157 Clinical trial, 5, 10, 13, 20, 83, 86, 117, 157, 187, 188 Clone, 92, 157 Cloning, 101, 152, 157 Cochlea, 100, 157, 172 Cochlear, 33, 101, 157, 195, 197 Cochlear Diseases, 157, 195 Coenzyme, 151, 157, 174, 191 Cofactor, 157, 187, 195 Collagen, 5, 6, 7, 9, 10, 11, 12, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 34, 35, 36, 37, 40, 43, 44, 45, 46, 47, 48, 50, 53, 54, 57, 58, 59, 61, 63, 65, 67, 68, 69, 72, 76, 81, 85, 90, 92, 97, 101, 120, 129, 132, 152, 155, 157, 159, 166, 182, 186 Collagen disease, 21, 157 Collapse, 153, 157, 192 Colloidal, 157, 164, 165 Coloboma, 157, 176 Complement, 20, 91, 149, 157, 158, 167, 172, 173, 175 Complementary and alternative medicine, 75, 79, 158 Complementary medicine, 75, 158 Computational Biology, 117, 119, 158 Computed tomography, 18, 31, 153, 158 Computerized axial tomography, 158 Computerized tomography, 158 Conduction, 151, 158 Cones, 158, 189 Confusion, 58, 158, 161 Congenita, 46, 101, 120, 159, 162 Congestive heart failure, 7, 159 Conjunctiva, 159, 162 Connective Tissue Cells, 159 Connective Tissue Diseases, 13, 159 Consolidation, 14, 159 Constitutional, 159, 178, 190 Constriction, 159, 173, 190

Contraindications, ii, 159 Coordination, 159, 178 Cornea, 159, 162, 191, 194 Corneum, 11, 159, 164 Coronary, 154, 159, 177, 179 Coronary heart disease, 154, 159 Coronary Thrombosis, 159, 177, 179 Cortex, 12, 151, 159, 165, 188, 189 Cortical, 20, 66, 102, 159, 191, 194 Corticosteroids, 159, 167 Cranial, 103, 159, 165, 168, 173, 181, 184, 197 Craniocerebral Trauma, 151, 159, 168, 170, 194, 195 Crossing-over, 160, 188 Curative, 22, 160, 190, 194 Cyclic, 35, 153, 160 Cyst, 4, 160, 181 Cysteine, 92, 160, 162 Cystine, 9, 160, 162 Cystostomy, 4, 160 Cytogenetics, 160, 190 Cytokines, 13, 94, 160 Cytoplasm, 150, 160, 163, 178, 179 Cytoskeleton, 160, 172 D Databases, Bibliographic, 117, 160 Defense Mechanisms, 160, 173 Degenerative, 90, 101, 160, 181, 189 Deletion, 7, 24, 35, 36, 150, 160, 166 Delivery of Health Care, 160, 168 Density, 5, 6, 15, 18, 20, 23, 31, 32, 35, 66, 84, 85, 130, 153, 160, 180 Dental Care, 98, 130, 160 Dental Caries, 4, 160, 192 Dental implant, 31, 161, 181 Dentin Dysplasia, 101, 161 Deoxyribonucleotides, 161, 180 Dermal, 40, 161, 162 Deuterium, 161, 170 Dexterity, 104, 161 Diagnostic procedure, 89, 108, 161 Diencephalon, 161, 183 Digestion, 45, 153, 161, 174, 193 Digestive system, 86, 161 Dihydrotestosterone, 161, 189 Dilatation, 149, 161, 186, 197 Dilation, 161, 170 Dimerization, 10, 161 Diploid, 161, 185, 196 Direct, iii, 14, 16, 19, 37, 72, 94, 111, 157, 161, 185, 189


Disability Evaluation, 18, 161 Disease Progression, 161, 189 Dislocation, 21, 150, 161 Disorientation, 158, 161 Dissociation, 147, 161 Distal, 23, 162, 187 Disulphide, 38, 162 Diuresis, 153, 162 Dizziness, 100, 162, 197 Dose-dependent, 94, 162 Drug Interactions, 112, 162 Duct, 162, 190 Dura mater, 162, 176, 182 Dwarfism, 83, 84, 126, 162, 194 Dyskeratosis Congenita, 102, 162 Dysostosis, 102, 162 Dysplasia, 90, 99, 100, 101, 102, 103, 121, 162 Dystrophic, 19, 162, 164 Dystrophy, 23, 121, 130, 131, 162 E Eardrum, 100, 162 Ectoderm, 162 Ectodermal Dysplasia, 101, 102, 162 Effector, 157, 162 Efficacy, 15, 20, 23, 24, 28, 40, 162 Elastin, 157, 159, 162 Electrolyte, 162, 192 Electrons, 151, 163, 173, 182, 188 Embolus, 163, 172 Embryo, 149, 153, 155, 162, 163, 165, 167, 172, 182, 186 Emulsion, 163, 166, 177 Enamel, 56, 148, 160, 163 Encephalocele, 42, 163 Endemic, 163, 193 Endothelial cell, 12, 163, 166, 195 Endothelium, 12, 163 Endothelium, Lymphatic, 163 Endothelium, Vascular, 163 Endotoxins, 158, 163 End-stage renal, 156, 163, 185 Energetic, 16, 164 Enhancer, 12, 164 Environmental Exposure, 164, 180 Environmental Health, 116, 118, 164 Enzymatic, 154, 158, 160, 164, 189 Enzyme, 148, 155, 157, 162, 164, 174, 177, 178, 186, 187, 189, 191, 195, 198 Epidemic, 164, 193 Epidermis, 159, 162, 164 Epidermolysis Bullosa, 22, 101, 102, 164

202

Epiphyseal, 90, 164 Epiphyses, 156, 164 Epithelial, 101, 162, 164, 188 Epithelium, 152, 163, 164, 173, 189 Epitopes, 17, 164 Erythrocytes, 149, 153, 164 Esophagus, 161, 164, 193 Essential Tremor, 121, 164 Etidronate, 39, 164 Eukaryotic Cells, 164, 171, 181 Evacuation, 106, 164 Exogenous, 19, 164, 167 Exon, 35, 58, 63, 148, 164 Expander, 43, 164 Extender, 165 Extensor, 165, 187 Extracellular, 7, 8, 20, 40, 41, 55, 67, 90, 159, 165, 166, 172, 181, 192 Extracellular Matrix, 7, 8, 20, 55, 67, 91, 159, 165, 166, 172, 181 Extracellular Space, 165 Extraction, 150, 165, 189 Extrapyramidal, 60, 165 Extremity, 55, 165, 183 F Facial, 100, 103, 165, 176, 183 Facial Nerve, 100, 165, 183 Facial Paralysis, 101, 165 Family Planning, 117, 165 Fat, 22, 153, 154, 159, 163, 165, 174, 178, 190, 192 Febrile, 50, 165, 193 Femoral, 6, 18, 57, 165, 169 Femoral Neck Fractures, 165, 169 Femur, 8, 23, 165, 169 Fetal Development, 6, 165 Fetus, 153, 165, 186, 197 Fibril, 8, 10, 16, 21, 35, 90, 165 Fibroblast Growth Factor, 94, 165 Fibroblasts, 10, 19, 25, 26, 40, 46, 64, 72, 73, 81, 92, 159, 166 Fibroma, 52, 166 Fibronectin, 77, 166 Fibrosis, 101, 121, 166, 190, 191 Fistula, 101, 103, 166 Fixation, 98, 100, 166 Fold, 90, 166 Fovea, 166 Fracture Healing, 6, 166 G Gallbladder, 161, 166 Gas, 154, 166, 170, 180, 187, 189

203

Gas exchange, 166, 189 Gastrin, 166, 170 Gelatin, 166, 167 Gene Deletion, 53, 166 Gene Expression, 19, 76, 122, 167 Gene Targeting, 9, 167 Generator, 75, 167, 194 Genetic Code, 167, 180 Genetic Engineering, 152, 157, 167 Genetic Screening, 16, 167 Genotype, 19, 60, 167, 184 Germ Cells, 92, 167, 182, 192 Germ Layers, 153, 162, 167 Gestation, 54, 157, 167, 184 Giant Cells, 94, 167, 190 Gland, 101, 167, 175, 183, 185, 186, 191, 193, 195 Glucocorticoid, 93, 167 Glucose, 121, 150, 167, 169 Glycine, 16, 24, 25, 28, 36, 43, 54, 92, 167 Glycoprotein, 69, 166, 167, 195 Glycosaminoglycans, 46, 168, 178, 187 Gout, 103, 168 Governing Board, 168, 186 Grade, 106, 168 Graft, 8, 31, 101, 168, 170 Grafting, 8, 168, 171 Granuloma, 101, 168 Gravis, 104, 168 Growth factors, 94, 168 Growth Plate, 19, 84, 168 H Handicap, 161, 168 Haplotypes, 68, 168 Haptens, 147, 168 Headache, 153, 168, 170 Health Care Costs, 16, 168, 169 Health Expenditures, 168 Health Promotion, 17, 169 Heart attack, 154, 169 Heart failure, 169 Hematopoiesis, 13, 169 Hemoglobin, 149, 164, 169 Hemoglobinuria, 121, 169 Hemorrhage, 42, 160, 168, 169, 193 Hemostasis, 169, 173 Hepatic, 169, 191 Hereditary, 4, 101, 148, 156, 159, 162, 168, 169, 185, 190 Heredity, 166, 167, 169 Heterodimers, 169, 172, 196 Heterogeneity, 45, 147, 169

Heterozygotes, 47, 169 Hip Fractures, 94, 165, 169 Histiocytosis, 100, 169 Histology, 6, 169 Homodimer, 169, 196 Homogeneous, 17, 170 Homologous, 10, 14, 17, 148, 160, 167, 169, 170, 191 Hormonal, 151, 170 Hormone therapy, 32, 46, 98, 170 Host, 8, 20, 21, 165, 170 Hybrid, 157, 170 Hybridization, 20, 170 Hydrocephalus, 104, 170, 173 Hydrogen, 9, 16, 151, 161, 170, 178, 180, 182, 184, 187 Hydroxylysine, 157, 170 Hydroxyproline, 21, 157, 170 Hyperbilirubinemia, 103, 170, 173 Hypercalcemia, 93, 164, 170 Hyperostosis, 100, 102, 170 Hyperplasia, 101, 170 Hypersensitivity, 170, 190 Hypertension, 154, 170, 173 Hyperthyroidism, 102, 170 Hypertrophy, 102, 170, 171 Hyperuricemia, 168, 171 Hypoplasia, 148, 162, 171, 176 I Id, 74, 78, 120, 130, 131, 132, 140, 142, 171 Idiopathic, 23, 52, 101, 171, 190 Illusion, 171, 197 Immune function, 171, 196 Immune response, 150, 151, 168, 171, 175, 194, 198 Immune system, 151, 152, 171, 175, 178, 197, 198 Immunoassay, 32, 171 Immunodeficiency, 121, 171 Immunofluorescence, 76, 171 Immunohistochemistry, 12, 171 Immunologic, 156, 171 Immunology, 147, 171 Immunosuppressant, 8, 171 Immunosuppressive, 93, 167, 171 Immunosuppressive therapy, 93, 171 Impairment, 3, 47, 98, 100, 104, 109, 151, 152, 171, 176 Implantation, 8, 10, 17, 33, 171 In situ, 8, 19, 20, 91, 171 In Situ Hybridization, 20, 171 In vitro, 7, 10, 11, 17, 19, 24, 94, 171, 195


In vivo, 7, 8, 9, 11, 12, 17, 19, 20, 24, 91, 94, 171 Incision, 171, 173 Incontinence, 170, 171 Incontinentia Pigmenti, 102, 172 Incus, 100, 172, 176, 193 Indicative, 19, 99, 172, 183, 197 Induction, 12, 172, 191 Infancy, 15, 156, 172, 190 Infantile, 102, 172 Infarction, 7, 155, 172 Infection, 101, 152, 156, 171, 172, 175, 190, 194, 198 Inflammation, 150, 156, 166, 172, 174, 176, 180, 182, 185, 190, 193 Infusion, 17, 20, 35, 40, 85, 172, 196 Inlay, 172, 189 Inner ear, 62, 84, 103, 153, 157, 172, 174, 176 Innervation, 165, 172 Inorganic, 172, 192 Insight, 6, 20, 172 Insulator, 172, 178 Integrins, 7, 172 Intermittent, 14, 173 Interstitial, 49, 165, 173 Intestinal, 154, 173, 175 Intoxication, 173, 198 Intracellular, 153, 172, 173, 175 Intracranial Hemorrhages, 170, 173, 194 Intracranial Hypertension, 168, 170, 173, 195 Intraepithelial, 101, 173 Intramuscular, 12, 173 Intramuscular injection, 12, 173 Intravenous, 15, 18, 23, 25, 30, 31, 38, 47, 51, 85, 172, 173 Intrinsic, 19, 147, 152, 173 Invasive, 8, 58, 173, 175 Involuntary, 23, 151, 164, 173, 179, 189 Ions, 151, 161, 162, 170, 173, 178 Iris, 159, 173, 191 Ischemia, 151, 173 J Jaundice, 170, 173 Joint, 32, 35, 37, 38, 44, 47, 59, 65, 69, 78, 90, 103, 150, 173, 175, 181, 194 K Karyotype, 53, 173 Kb, 92, 116, 173 Keratolytic, 161, 173 Kidney Disease, 86, 116, 121, 173

204

Kilobase, 92, 173 Kinetics, 32, 38, 174 Kink, 28, 174 L Labile, 157, 174 Labyrinth, 100, 157, 172, 174, 182, 184, 191, 197 Labyrinthitis, 101, 174 Lacrimal, 165, 174 Large Intestine, 161, 174, 188, 192 Latent, 174, 186 Lens, 150, 155, 159, 174, 189, 198 Lesion, 168, 174 Lethal, 15, 26, 27, 28, 35, 43, 45, 50, 53, 54, 67, 68, 69, 73, 92, 174 Lethargy, 170, 174 Leukemia, 41, 92, 120, 174, 178 Leukocytes, 153, 156, 160, 174, 178 Library Services, 140, 174 Ligament, 174, 186 Ligands, 11, 172, 174 Linkage, 54, 65, 68, 174 Lip, 102, 104, 174 Lipid, 11, 174, 178 Liver, 131, 151, 161, 163, 166, 169, 174, 190 Localization, 20, 49, 54, 67, 171, 174 Localized, 109, 160, 166, 172, 174, 185 Lovastatin, 94, 174, 191 Low-density lipoprotein, 174, 175 Lumbar, 37, 175 Lupus, 157, 175 Luxation, 161, 175 Lymph, 156, 163, 175, 190 Lymph node, 156, 175, 190 Lymphatic, 163, 172, 175, 177, 193 Lymphocyte, 150, 175, 176 Lymphoid, 150, 159, 175 Lymphoma, 120, 175 Lysine, 170, 175, 186 Lysosomal Storage Diseases, 175, 178 M Macrophage, 94, 175 Magnetic Resonance Imaging, 51, 175 Major Histocompatibility Complex, 168, 175 Malabsorption, 121, 175 Malformation, 100, 175 Malignancy, 93, 175 Malignant, 120, 153, 169, 175, 179 Malleus, 172, 176 Malnutrition, 151, 176, 178 Mammogram, 154, 176, 177

205

Mandible, 4, 14, 148, 176, 189 Mandibulofacial Dysostosis, 101, 102, 176 Mastication, 14, 176 Meatus, 162, 176, 196 Medial, 176, 195 Mediate, 13, 176 Mediator, 24, 176 MEDLINE, 117, 119, 121, 176 Megakaryocytes, 153, 176 Melanocytes, 176, 180 Melanoma, 120, 176 Membrane, 22, 149, 156, 158, 159, 162, 164, 176, 178, 181, 184, 189, 196 Meninges, 155, 159, 162, 176 Meningitis, 101, 103, 176 Menopause, 176, 185 Mental Disorders, 87, 176, 187 Mental Processes, 161, 176, 187 Mental Retardation, 60, 122, 176 Mesenchymal, 8, 9, 13, 14, 17, 20, 22, 25, 52, 66, 68, 77, 176 Metabolic disorder, 168, 177 Metabolite, 174, 177 Metastasis, 177 MI, 91, 93, 145, 177 Microbiology, 147, 177 Microcalcifications, 154, 177 Microorganism, 157, 177, 198 Micro-organism, 161, 177 Microradiography, 37, 177 Microscopy, 7, 8, 19, 37, 56, 152, 177 Migration, 13, 94, 177 Milliliter, 153, 177 Millimeter, 18, 177 Mineralization, 17, 18, 30, 35, 37, 66, 177, 182 Mitochondrial Swelling, 177, 179 Mitosis, 150, 177 Mitral Valve, 25, 53, 177 Mobility, 104, 106, 129, 177 Modeling, 12, 25, 56, 177 Modification, 11, 167, 178, 188 Molecular, 6, 8, 12, 16, 21, 50, 58, 60, 65, 68, 101, 117, 119, 152, 158, 160, 164, 165, 178 Molecular Structure, 16, 21, 178 Molecule, 8, 21, 150, 151, 152, 157, 158, 161, 162, 178, 180, 182, 185, 187, 188, 197 Monitor, 65, 178, 180 Monocytes, 6, 174, 178 Mononuclear, 168, 178 Morphological, 37, 77, 163, 176, 178

Mosaicism, 45, 60, 69, 178 Mucopolysaccharidoses, 100, 102, 178 Mucosa, 102, 175, 178, 194 Multiple sclerosis, 104, 178 Muscle Fibers, 178, 179 Muscular Atrophy, 121, 178 Muscular Diseases, 165, 178 Muscular Dystrophies, 104, 162, 178 Musculoskeletal System, 13, 178, 181 Myasthenia, 104, 178 Myelin, 178 Myelodysplasia, 23, 178 Myelogenous, 178, 179 Myocardial infarction, 159, 177, 179, 197 Myocardium, 7, 177, 179 Myofibrils, 7, 179 Myopia, 179, 189 Myosin, 12, 179 Myotonic Dystrophy, 121, 179 N NCI, 1, 86, 115, 156, 179 Necrosis, 101, 150, 155, 172, 177, 179, 190 Need, 3, 19, 84, 93, 97, 99, 105, 109, 127, 129, 130, 134, 147, 156, 179 Neonatal, 7, 13, 179, 194 Neonatal period, 179, 194 Neoplasia, 102, 120, 179 Neoplasm, 179 Neoplastic, 92, 149, 175, 179 Nephropathy, 173, 179 Nerve, 149, 151, 165, 172, 176, 178, 179, 181, 191, 193, 196, 197 Nervous System, 121, 147, 155, 176, 179, 180, 184 Neural, 13, 147, 163, 179, 189 Neurologic, 163, 170, 179 Neuronal, 13, 179 Neurons, 179, 197 Neuroretinitis, 180, 190 Neutrons, 148, 180, 188 Nevus, 101, 180 Night Blindness, 180, 190 Nitrogen, 94, 166, 180, 196 Nuclear, 59, 67, 69, 151, 163, 164, 179, 180 Nuclear Family, 69, 180 Nuclei, 148, 163, 165, 167, 175, 177, 180, 181, 187, 197 Nucleic acid, 91, 167, 170, 171, 180 Nucleic Acid Hybridization, 170, 180 Nucleus, 150, 151, 156, 160, 161, 164, 178, 180, 187, 193, 194, 197


O Occupational Therapy, 106, 180 Oligodeoxyribonucleotides, 92, 180 Oncogene, 92, 120, 180 Oncogenic, 173, 180 Opacity, 155, 160, 180 Ophthalmology, 47, 55, 166, 180, 189 Opsin, 180, 189 Optic cup, 180, 183 Optic Nerve, 180, 181, 182, 183, 189, 190, 191 Oral Health, 103, 104, 181 Organ Culture, 181, 195 Organelles, 160, 176, 178, 181 Orofacial, 102, 181 Orthopaedic, 8, 11, 20, 34, 39, 41, 43, 56, 61, 72, 91, 126, 181 Orthopedics, 27, 30, 38, 39, 43, 44, 50, 51, 55, 58, 64, 76, 181 Osseointegration, 153, 181 Ossicles, 172, 176, 181, 182, 193 Ossification, 181, 182, 190 Osteitis Fibrosa Cystica, 100, 181 Osteoarthritis, 11, 21, 90, 93, 98, 101, 103, 181 Osteoblasts, 6, 9, 13, 20, 41, 50, 55, 72, 76, 93, 181 Osteocalcin, 19, 20, 24, 181 Osteochondrodysplasias, 29, 181 Osteoclasts, 6, 93, 181 Osteocytes, 11, 181 Osteodystrophy, 99, 182 Osteolysis, 93, 182 Osteomalacia, 103, 104, 182 Osteopetrosis, 99, 102, 103, 182 Osteoporosis, 9, 11, 16, 21, 23, 25, 31, 52, 79, 90, 91, 92, 93, 98, 103, 104, 126, 127, 128, 130, 131, 148, 182 Osteotomy, 14, 64, 182 Otitis, 101, 103, 182 Otitis Media, 101, 103, 182 Otolaryngologist, 99, 100, 182 Otolaryngology, 33, 52, 63, 99, 100, 182 Otology, 3, 29, 46, 47, 64, 65, 99, 100, 182 Otorrhea, 100, 182 Otosclerosis, 29, 64, 84, 100, 103, 182 Ovary, 182, 194 Overexpress, 8, 182 Ovum, 167, 182, 198 Oxidation, 160, 162, 182 P Pachymeningitis, 176, 182

206

Paediatric, 27, 34, 37, 52, 56, 61, 182 Palate, 102, 104, 183 Palliative, 183, 194 Palsy, 23, 104, 183 Pamidronate, 18, 25, 31, 35, 38, 40, 47, 48, 49, 51, 56, 61, 62, 85, 108, 183 Pancreas, 161, 183 Pancreatic, 120, 183 Pancreatic cancer, 120, 183 Parathyroid, 183, 190 Parathyroid Glands, 183, 190 Paresis, 165, 183 Parotid, 183, 190 Paroxysmal, 121, 183 Patella, 64, 183 Paternal Age, 39, 40, 108, 183 Pathogenesis, 8, 100, 101, 102, 183 Pathologic, 102, 150, 152, 154, 159, 170, 183, 185, 187, 189 Pathologic Processes, 150, 183 Pathologies, 101, 183 Patient Advocacy, 133, 183 Patient Education, 128, 138, 140, 145, 183 Pedicle, 65, 183 Pelvic, 184, 186 Peptide, 10, 21, 22, 165, 184, 185, 186, 187 Percutaneous, 9, 61, 184 Perforation, 100, 184 Pericytes, 12, 184 Perilymph, 101, 184 Perinatal, 54, 92, 103, 184 Periodontal disease, 148, 184 Peripheral blood, 6, 184 Peripheral Nervous System, 183, 184, 194 Personnel, Hospital, 133, 184 PH, 25, 26, 27, 36, 38, 40, 42, 43, 44, 50, 51, 53, 63, 69, 153, 184 Phallic, 166, 184 Pharmacologic, 18, 98, 149, 184, 195 Phenotype, 13, 16, 19, 24, 25, 31, 55, 60, 68, 92, 167, 184 Phospholipids, 165, 184 Phosphorus, 154, 183, 184 Physical Examination, 85, 184 Physical Therapy, 129, 184 Physiologic, 152, 165, 184, 188, 189 Physiology, 22, 185 Pigment, 152, 176, 185, 189 Pituitary Gland, 165, 185 Plants, 154, 155, 167, 185, 196 Plasma, 150, 163, 165, 166, 169, 185, 191 Plasma cells, 150, 185

207

Plasmids, 92, 185 Point Mutation, 37, 69, 185 Polyarthritis, 103, 185 Polycystic, 121, 185 Polymorphism, 53, 185 Polypeptide, 148, 149, 154, 157, 170, 185, 186, 198 Polysaccharide, 150, 185, 187 Pons, 165, 185 Porosity, 12, 18, 185 Posterior, 149, 151, 156, 173, 183, 185, 191 Postmenopausal, 25, 148, 182, 185 Postnatal, 7, 103, 185, 193 Postoperative, 50, 100, 185 Postoperative Complications, 100, 185 Practice Guidelines, 118, 130, 131, 185 Preclinical, 13, 186 Precursor, 6, 162, 164, 186, 196 Predisposition, 90, 186 Prenatal, 37, 42, 45, 51, 58, 62, 65, 69, 97, 98, 103, 163, 167, 186 Prenatal Diagnosis, 37, 42, 45, 51, 58, 62, 65, 186 Prevalence, 23, 104, 132, 186 Probe, 19, 27, 186 Procollagen, 21, 24, 25, 26, 31, 35, 36, 37, 38, 54, 61, 66, 72, 73, 186 Progeny, 22, 186 Progression, 149, 186 Progressive, 13, 15, 103, 156, 168, 178, 179, 181, 186, 190 Proline, 157, 170, 186 Promoter, 12, 92, 186 Prostate, 120, 186 Prosthesis, 101, 186 Protease, 45, 186 Protein C, 22, 90, 148, 181, 186 Protein Conformation, 148, 186 Protein Folding, 57, 186 Protein Isoforms, 148, 187 Protein S, 121, 122, 152, 167, 181, 186, 187 Proteoglycan, 7, 28, 35, 187 Proteolytic, 158, 187 Protocol, 16, 187 Protons, 148, 170, 187, 188 Proximal, 162, 187 Psoriasis, 101, 187 Psychiatry, 29, 166, 187 Psychology, 98, 161, 187 Psychomotor, 163, 187 Public Policy, 117, 187 Publishing, 24, 100, 101, 187

Pulmonary, 103, 152, 187, 189, 197 Pulmonary hypertension, 103, 187 Pulmonary Ventilation, 187, 189 Pulse, 14, 24, 75, 178, 187 Purulent, 182, 188 Pyramidal Tracts, 165, 188 Q Quality of Life, 133, 188 Quaternary, 186, 187, 188 Quiescent, 12, 188 R Race, 173, 177, 188 Radiation, 18, 147, 164, 188, 198 Radiation therapy, 147, 188 Radicular, 4, 188 Radicular Cyst, 4, 188 Radioactive, 153, 170, 171, 180, 188 Radiological, 4, 184, 188 Radiology, 32, 40, 48, 49, 57, 58, 60, 61, 62, 64, 188 Radiopharmaceutical, 167, 188 Randomized, 162, 188 Receptor, 6, 94, 147, 150, 188 Recombinant, 11, 63, 188, 197 Recombination, 14, 17, 68, 167, 188 Rectum, 153, 161, 166, 171, 174, 186, 188 Recurrence, 101, 188, 189 Red Nucleus, 151, 188 Reductase, 94, 174, 189, 191 Refer, 1, 157, 162, 166, 174, 180, 185, 189, 197 Reflex, 130, 131, 189 Regeneration, 4, 20, 91, 166, 189 Regimen, 13, 15, 162, 189 Remission, 188, 189 Reoperation, 32, 189 Reproductive cells, 167, 189 Research Support, 92, 189 Resolving, 27, 177, 189 Resorption, 8, 18, 32, 93, 148, 170, 181, 189 Respiratory System, 85, 189 Restoration, 18, 166, 184, 189, 198 Retina, 156, 158, 174, 179, 180, 181, 189, 190, 198 Retinal, 55, 181, 189 Retinal Detachment, 55, 189 Retinitis, 103, 190 Retinitis Pigmentosa, 103, 190 Retinoblastoma, 120, 190 Retinol, 189, 190 Rheumatism, 190 Rheumatoid, 103, 157, 190


Rheumatoid arthritis, 103, 157, 190 Rickets, 103, 104, 190 Rod, 55, 64, 65, 98, 151, 190 S Saline, 18, 190 Saliva, 190 Salivary, 101, 161, 165, 183, 190 Salivary glands, 161, 165, 190 Sarcoidosis, 100, 190 Satellite, 12, 190 Schizoid, 190, 198 Schizophrenia, 190, 198 Schizotypal Personality Disorder, 190, 198 Sclera, 33, 156, 159, 191 Sclerae, 41, 49, 58, 84, 120, 182, 191 Sclerosis, 121, 157, 178, 191 Scoliosis, 23, 64, 90, 191 Screening, 11, 37, 157, 167, 191 Secretion, 25, 38, 162, 191, 196 Segregation, 188, 191 Seizures, 183, 191 Semen, 186, 191 Semicircular canal, 172, 191 Senile, 182, 191 Sequencing, 37, 101, 191 Serologic, 171, 191 Serous, 163, 191 Serum, 69, 149, 157, 175, 181, 191 Sex Determination, 121, 191 Shock, 191, 196 Side effect, 93, 111, 147, 152, 171, 191, 195 Signs and Symptoms, 98, 189, 191 Simvastatin, 94, 191 Skeletal, 4, 9, 12, 19, 20, 48, 57, 61, 62, 63, 76, 100, 103, 120, 162, 178, 179, 181, 192 Skeleton, 100, 147, 165, 173, 192 Skin Abnormalities, 21, 192 Skull, 153, 160, 163, 192, 194 Sleep apnea, 52, 192 Small intestine, 170, 192, 197 Smooth muscle, 12, 19, 149, 153, 159, 178, 184, 192, 194 Social Environment, 188, 192 Sodium, 44, 153, 168, 192 Sodium Fluoride, 44, 192 Soft tissue, 11, 153, 192, 195 Solvent, 76, 192 Soma, 192 Somatic, 69, 92, 177, 184, 192 Somatic cells, 92, 177, 192 Spatial disorientation, 162, 192 Specialist, 134, 161, 192

208

Species, 148, 155, 170, 173, 177, 185, 188, 192, 196, 198 Specificity, 147, 192 Spectrum, 178, 192 Sperm, 156, 189, 193 Spina bifida, 23, 104, 193 Spinal cord, 155, 156, 162, 176, 179, 182, 184, 188, 189, 193 Spinal Injuries, 104, 193 Spleen, 175, 190, 193 Splenomegaly, 182, 193 Spondylitis, 103, 193 Spontaneous Fractures, 4, 193 Sporadic, 40, 190, 193 Sprue, 130, 193 Stabilization, 21, 193 Stapes, 63, 65, 67, 100, 172, 193 Stem Cells, 8, 9, 12, 14, 17, 20, 22, 44, 76, 107, 148, 193 Steroid, 191, 193 Stimulant, 153, 193 Stimulus, 172, 189, 193 Stippling, 156, 193 Stoma, 160, 193 Stomach, 161, 164, 166, 170, 192, 193 Strand, 9, 193 Stress, 154, 186, 190, 193 Stroke, 87, 104, 116, 154, 193 Stroma, 22, 173, 194 Stromal, 13, 14, 17, 25, 39, 55, 64, 94, 153, 194 Stromal Cells, 13, 14, 17, 25, 39, 55, 64, 94, 153, 194 Subacute, 172, 194 Subclinical, 172, 191, 194 Subcutaneous, 17, 194 Substance P, 177, 191, 194 Subtrochanteric, 169, 194 Supplementation, 78, 194 Support group, 133, 194 Symphysis, 186, 194 Synchrotron, 18, 194 Syncytium, 167, 194 Systemic, 17, 103, 112, 150, 152, 157, 172, 173, 188, 190, 194 Systemic disease, 103, 194 T Telangiectasia, 101, 121, 194 Temporal, 32, 99, 100, 176, 194 Testosterone, 189, 194 Thalamic, 151, 194 Thalamic Diseases, 151, 194

209

Thanatophoric Dysplasia, 39, 194 Therapeutics, 77, 112, 194 Thermal, 26, 59, 161, 180, 194 Thigh, 165, 195 Thorax, 147, 175, 195 Thrombin, 186, 195 Thrombomodulin, 186, 195 Thrombosis, 173, 187, 193, 195 Thrombus, 159, 172, 195 Thyroid, 101, 170, 183, 195 Thyroid Gland, 101, 170, 183, 195 Thyroid Hormones, 195 Tibiae, 20, 195 Tinnitus, 101, 182, 195, 197 Tissue Culture, 20, 195 Tissue Expansion, 41, 195 Tomography, 18, 195 Tooth Preparation, 147, 195 Torsion, 172, 195 Toxic, iv, 162, 164, 195 Toxicity, 162, 195 Toxicology, 118, 195 Toxins, 150, 163, 172, 196 Trachea, 195, 196 Transfection, 152, 196 Transforming Growth Factor beta, 39, 196 Transfusion, 165, 196 Transmitter, 176, 196 Transplantation, 9, 13, 156, 175, 196 Trauma, 23, 41, 84, 104, 179, 195, 196 Trisomy, 102, 196 Tryptophan, 157, 196 Tuberous Sclerosis, 102, 121, 196 Tympanic membrane, 100, 176, 181, 196 U Unconscious, 160, 171, 196 Urethra, 186, 196 Uric, 168, 171, 196 Urinary, 32, 68, 154, 160, 170, 171, 196 Urine, 69, 152, 162, 169, 171, 196 Uterine Rupture, 34, 55, 196 Uterus, 156, 197

V Vaccine, 187, 197 Vascular, 12, 14, 19, 156, 163, 172, 195, 197 Vector, 10, 197 Vein, 85, 149, 173, 180, 183, 190, 197 Venous, 155, 187, 197 Ventricle, 150, 177, 187, 197 Ventricular, 7, 25, 53, 170, 197 Ventricular Remodeling, 7, 197 Venules, 152, 154, 163, 197 Vertebrae, 193, 197 Vertebral, 18, 37, 61, 69, 152, 193, 197 Vertigo, 100, 182, 197 Vestibular, 69, 100, 197 Vestibule, 157, 172, 191, 197 Vestibulocochlear Nerve, 195, 197 Vestibulocochlear Nerve Diseases, 195, 197 Veterinary Medicine, 117, 197 Villi, 170, 197 Viral, 167, 180, 198 Virus, 9, 92, 155, 164, 167, 198 Viscera, 192, 198 Visual field, 190, 198 Vitreous Humor, 189, 198 Vitro, 7, 19, 24, 94, 198 Vivo, 10, 19, 68, 94, 198 Volition, 173, 198 W White blood cell, 150, 174, 175, 185, 198 Windpipe, 195, 198 Withdrawal, 39, 198 Wound Healing, 19, 166, 173, 198 X Xenograft, 149, 198 X-ray, 18, 20, 21, 27, 66, 85, 130, 144, 153, 158, 176, 180, 188, 198 Y Yeasts, 184, 198 Z Zygote, 178, 198 Zymogen, 186, 198


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