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

CRANIOSYNOSTOSIS 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., 1960Craniosynostosis: 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: 0-497-00309-0 1. Craniosynostosis-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 craniosynostosis. 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 CRANIOSYNOSTOSIS ................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Craniosynostosis ........................................................................... 4 The National Library of Medicine: PubMed ................................................................................ 26 CHAPTER 2. ALTERNATIVE MEDICINE AND CRANIOSYNOSTOSIS ................................................. 71 Overview...................................................................................................................................... 71 National Center for Complementary and Alternative Medicine.................................................. 71 Additional Web Resources ........................................................................................................... 73 General References ....................................................................................................................... 73 CHAPTER 3. DISSERTATIONS ON CRANIOSYNOSTOSIS ................................................................... 75 Overview...................................................................................................................................... 75 Dissertations on Craniosynostosis............................................................................................... 75 Keeping Current .......................................................................................................................... 75 CHAPTER 4. BOOKS ON CRANIOSYNOSTOSIS .................................................................................. 77 Overview...................................................................................................................................... 77 Book Summaries: Federal Agencies.............................................................................................. 77 Book Summaries: Online Booksellers........................................................................................... 78 Chapters on Craniosynostosis...................................................................................................... 78 CHAPTER 5. MULTIMEDIA ON CRANIOSYNOSTOSIS ....................................................................... 81 Overview...................................................................................................................................... 81 Video Recordings ......................................................................................................................... 81 CHAPTER 6. PERIODICALS AND NEWS ON CRANIOSYNOSTOSIS .................................................... 83 Overview...................................................................................................................................... 83 News Services and Press Releases................................................................................................ 83 Newsletters on Craniosynostosis ................................................................................................. 85 Academic Periodicals covering Craniosynostosis ........................................................................ 85 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 89 Overview...................................................................................................................................... 89 NIH Guidelines............................................................................................................................ 89 NIH Databases............................................................................................................................. 91 Other Commercial Databases....................................................................................................... 93 The Genome Project and Craniosynostosis .................................................................................. 93 APPENDIX B. PATIENT RESOURCES ................................................................................................. 97 Overview...................................................................................................................................... 97 Patient Guideline Sources............................................................................................................ 97 Finding Associations.................................................................................................................. 100 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 103 Overview.................................................................................................................................... 103 Preparation................................................................................................................................. 103 Finding a Local Medical Library................................................................................................ 103 Medical Libraries in the U.S. and Canada ................................................................................. 103 ONLINE GLOSSARIES................................................................................................................ 109 Online Dictionary Directories ................................................................................................... 110 CRANIOSYNOSTOSIS DICTIONARY.................................................................................... 111 INDEX .............................................................................................................................................. 151

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

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

Craniosynostosis: Part I: Sagittal Synostosis Source: FACES. 7(1): 5. Winter 1993. Contact: Available from National Association for the Craniofacially Handicapped. P.O. Box 11082, Chattanooga, TN 37401. (615) 266-1632; (800) 332-2373. Summary: Craniosynostosis can be defined as the premature closing of one or more of the normally present bony gaps between the different bones of the skull. This brief article discusses the diagnosis of craniosynostosis, saggital synostosis, and the surgical treatment of infants with isolated craniosynostosis. The author emphasizes that these infants are best evaluated and treated by a craniofacial center that utilizes a multidisciplinary team approach.

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

Project Title: ANIMAL MODELS FOR SAETHRE CHOTZEN SYNDROME Principal Investigator & Institution: Gridley, Thomas H.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2002 Summary: The long term goals of this project are to generate and characterize mouse models of human craniofacial disease syndromes, and to understand the genetic and biochemical pathways underlying these disease syndromes. Craniosynostosis, the premature fusion of the calvarial bones of the skull, is a significant medical problem, occurring in 1 in 3000 live births. The abnormal skull growth associated with craniosynostosis may result in raised intracranial pressure, impaired cerebral blood flow, airway obstruction, impaired vision and hearing learning difficulties and adverse psychological effects. In this proposal, we will study a mouse model for SaethreChotzen Syndrome, one of the most common autosomal dominant disorders of craniosynostosis in humans. Haploinsufficiency for the human TWIST gene, which encodes a bHLH-type transcription factor, has been demonstrated to be one of the major causes of Saethre-Chotzen Syndrome. Other familial cases of Saethre-Chotzen Syndrome are caused by mutations in some of the genes encoding fibroblast growth factor receptors (FGR2 and FGR3). A null mutation in the mouse Twist gene results in early embryonic death in homozygotes, and in heterozygotes results in partially penetrant skeletal defects that replicate certain features of Saethre-Chotzen syndrome. The human TWIST gene is a homolog of the Twist gene of Drosophila. Genetic evidence in Drosophila has demonstrated that mutations in the Twist gene interact with mutations in another transcription factor encoded by the Snail gene. We have constructed targeted mutations in two mouse homologs of Snail (termed Sna and Slug). We will test the hypothesis that, as in Drosophila, genes of the Snail and Twist family both function in the same genetic pathway in mice. The specific aims of this proposal are to: 1. Further characterize Twist mutant embryos by testing fro altered expression of the Snail family genes Sna and Slug. Also examine whether expression of other genes responsible for inherited craniosynostosis syndromes (the fibroblast growth factor receptors and the

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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Msx genes) are altered in Twist mutant embryos. 2. Test the hypothesis that, as in Drosophila, genes of the Twist and Snail families will function in the same genetic pathway by generating and analyzing Sna/Twist double mutants. 3. Generate and analyze double mutants with the mother mouse Snail family gene Slug (Slug/Twist double mutants). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CEPHALOMETER FOR RAPID, SAFE MEASUREMENT OF INFANT HEAD Principal Investigator & Institution: Goldie, James H.; Foster-Miller, Inc. 350 2Nd Ave Waltham, Ma 02451 Timing: Fiscal Year 2004; Project Start 15-MAY-2004; Project End 14-NOV-2004 Summary: (provided by applicant): A cranial measurement device, or cephalometer is proposed that will provide a safe and convenient means for screening for and determining the severity and nature of plagiocephaly in an infant. Currently, initial screening by pediatricians is entirely subjective. The first quantitative evaluation is typically done with large calipers by a neurosurgeon or by radiographic means. However, there is need for an inexpensive device that either clinicians or parents can use to rapidly obtain accurate and repeatable data, both for screening and during the course of treatment. The proposed measurement device offers a practical method for obtaining frequent measurements, allowing the treating physician to evaluate the progress and effectiveness of treatment. This will benefit patients with conditions ranging in significance from deformational plagiocephaly, treated with orthotic devices such as helmets, to sagittal synostosis, a congenital skull abnormality requiring surgery. Although not a requirement, the proposed device can be upgraded to include sensors, data acquisition and a computer, in order to create a complete system in which measurements are displayed, evaluated, and diagnostic and record-keeping tasks undertaken. The Phase I will focus on development and test of several cephalometer prototypes. Testing will be done with infant head models that represent both normal head shapes and deformities of interest, in order to evaluate rapidity of measurement, measurement accuracy and repeatability (as compared with calipers and other accepted methods), measurement quality as a function of user's level of training (again, compared with existing methods), and device cost. Testing with infants will be deferred until the Phase II, in which measurements will be taken on many infants with a wide range of head shapes by parents, doctors, and other clinicians. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COPING WITH CRANIOFACIAL DISORDERS Principal Investigator & Institution: Slifer, Keith J.; Kennedy Krieger Institute, Inc. 707 N Broadway Baltimore, Md 21205 Timing: Fiscal Year 2002 Summary: Children with craniofacial disorders have increased incidence of anxiety, withdrawal and social competence problems, but they tend to rate their own appearance more positivity than it is rated by others. Some may learn to cope with facial impairment by minimizing it an developing compensatory behavior. Direct observations of these children reveal social interactions that differ significantly from peers. Other data suggest they have impaired ability to communicate emotion through facial expressions. This study will employ: (1) microanalytic direct observation methods, and (2) computerautomated recognition of facial expressions to quantify the social and facial behavior of

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8 to 16 year-old subjects videotaped during: (1) an analogue social interaction with a confederate peer, and (2) a structured facial encoding task. Results will be compared across matched Craniofacial (oral cleft and craniosynostosis). Non-facial (short stature), and Normal Control groups. Within-group comparisons will examine ow subjects with positive self-perceptions differ from those with comparable physical impairments and average or negative self-perceptions. Differences in self ratings of appearance and selfconcept are expected to be significantly correlated with observable differences in social behavior. Craniofacial subjects (particularly those with oral clefts) are expected to evidence impaired ability to encode emotion through facial expressions. Some differences in social and facial behavior may reflect compensatory behavior developed by those who are better-adjusted and more socially competent, which could be taught those who are less competent. If differences in ability to generate facial expression are found in subjects with craniofacial disorders, and associated with impaired social competence, the results may lead to assessment techniques for detecting subtle but clinically significant facial dysfunction. Some may be amenable to surgical correction, others to behavioral intervention (e.g. response shaping with reinforcement contingencies or biofeedback training of facial muscles). Such intervention could be tested by subsequent demonstration projects. The combined results will provide an empirical basis for selecting specific skills to be taught in future prospective interventions for children with craniofacial disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL Principal Investigator & Institution: Vander Kolk, Craig; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: The overall goal of the Clinical Core is to be the organizational structure to collate information and specimens on patients with craniosynostosis and oral clefting and associated dental and facial anomalies. Patients will participate in our research projects from the Mid-Atlantic (Maryland, Washington D.C., Virginia) and Midwest (Missouri) REGIONS OF THE United States, Denmark, Czech Republic, Mexico, and Argentina. Databases will include information on phenotype, diagnosis, and classification of these individuals. The condition of the patient will be classified as sporadic or familial, isolated or syndromic (and whether the syndrome is recognized or previously unknown), or environmental in origin. Salient medical, surgical, dental, and family history information will be retained in the database. 3D CAT and brain morphology scans will also be entered into the database for patients with craniosynostosis. Using this data, patients will be triaged for future studies, such as chromosomal analysis, molecular DNA analysis, questionnaire of environmental factors, and behavioral analysis. The database will be used by Projects V, VI, VII, and VIII of this Center, in order to correlate genotypes with phenotypes, environmental, and behavioral factors, develop accurate diagnostic criteria, and map and clone genes responsible for isolated, familial, and syndromic craniosynostosis and multiplex families with oral clefting. To implement this project 1) patients with craniosynostosis or oral clefting and their families will be ascertained and enrolled, 2) medical and family histories and radiology test results will be entered into the database, and 3) blood samples will be obtained for chromosome analysis, DNA isolation, and establishment of a lymphoblast cell line and potential other tissue cell lines from surgical specimens for future analysis. Outpatient clinics through the Johns Hopkins Cleft & Craniofacial Center, the Johns Hopkins Division of Dentistry and Oral & Maxillofacial Surgery, the Center for Medical

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Genetics in Rockville, Maryland, the University of Maryland Medical Center and Virginia Commonwealth University's School of Dentistry and Center for Facial Reconstruction will be utilized to recruit patients for these research projects. The collaborative research efforts will identify, isolate and characterize genetic, environmental, and behavioral factors essential in craniofacial development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CRANIOFACIAL DEVELOPMENTAL MOLECULAR BIOLOGY Principal Investigator & Institution: Shuler, Charles F.; Ctr/Craniofacial Molec Biol; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The Craniofacial Developmental Molecular Biology Program will consist of investigators from the University of Southern California, Schools of Dentistry and Medicine who participate in a multi-disciplinary research team focused on investigations of craniofacial genetics and developmental biology. The faculty collaboration includes investigators from the USC Institute of Genetic Medicine, the USC Comprehensive Cancer Center and the USC Center for Craniofacial Molecular Biology. The overall Program theme will use molecular biology approaches to investigate fundamental mechanisms required for normal development of the craniofacial complex. These findings will be applicable to further the understanding of normal developmental regulation and the molecular etiology of craniofacial birth defects. The Craniofacial Developmental Molecular Biology Program will consist of five Research Projects and one Core Resource. Project 1 (Dr. Yang Chai), "Characterization of Genes Involved in the Specification of Tooth and Meckel's Cartilage Morphogenesis," will characterize the Smad- related intracellular signaling pathway that is activated during mandibular morphogenesis. Project 2 (Dr. Larry Kedes) "Co-Activators and Repressors of Muscle Transcription," will investigate the activity of Twist, p300/CBP and PCAF during the differentiation of muscle cells. Project 3 (Dr. Yi-Hsin Liu) "Genes Involved in Skull Suture Morphogenesis," will examine patters of gene expression unique to the cranial sutures that may be correlated with abnormal suture development resulting in craniosynostosis. Project 4 (Dr. Robert Maxon) "Function of MSX2 and Twist in Calvarial Morphogenesis," will examine the regulation and activation of interacting transcription factors Twist and Msx2 during bone cell commitment and differentiation. Project 5 (Dr. Charles Shuler) " Mechanisms of Epithelial-Mesenchymal Transformation during Palatogenesis," will investigate the molecular mechanism underlying the epithelial-mesenchymal transdifferentiation of the medial edge epithelium during palatal fusion. The activities of the Program will be supported by an Administrative Core that will provide support for purchasing, manuscript preparation, scheduling for seminars and collaborative research planning and financial management. The Program will benefit from the availability of several other established cores at the University of Southern California available to support the research activities of all the Projects. This program will continue a long-term series of collaborations that have provided an excellent scientific environment to advanced the understanding of the molecular mechanisms underling craniofacial development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CRANIOSYNOSTOSIS AND SUTURE BIOLOGY Principal Investigator & Institution: Cunningham, Michael L.; Associate Professor; University of Washington Grant & Contract Services Seattle, Wa 98105

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Timing: Fiscal Year 2002 Summary: Craniosynostosis is the morbid condition of premature fusion of calvarial bones. The sequelae of premature calvarial sutural fusion include 1) increased intracranial pressure associated with brain injury, 2) skull malformations requiring extensive surgical correction, and 3) abnormal development of the zygoma and maxilla necessitating orthodontic management and orthognatic surgery. Despite the rapid advance of our understanding of the molecular etiology of hereditary synostosis, the biological basis of craniosynostosis has yet to be elucidated. Over the past four years we have learned that mutations of fibroblast growth factor receptor family (FGFRs) and the TWIST are responsible for the majority of cases of syndromic synostosis. In order to understand the biology behind hereditary suture fusion, we propose to: 1) determine whether osteoblasts derived from patients with syndromic synostosis, harboring FGFR2, FGFR3, or TWIST mutations, will induce premature closure of rat coronal sutures 2) establish whether changes in suture development induced by mutant osteoblasts are due to intrinsic differences in mutant osteoblast growth and bone formation (e.g. cell autonomous) or the elaboration of cytokines which effect suture development and 3) correlate changes induced in suture development by mutant osteoblasts with changes in apoptotic cell death, mitogenic activity, and/or rates of matrix formation or mineralization. In order to test the hypothesis that: Syndromic craniosynostosis in humans is mediated by osteoblasts and their influence on the microenvironment of the calvarial suture. We propose that changes in osteoblast growth, mitotic rate, resistance to apoptosis and/or elaboration of cytokines results in premature suture fusion and craniosynostosis. These studies will lead to important information about the biology behind the development of craniosynostosis and may have significant implications for the treatment and primary prevention of synostosis in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DYSFUNCTIONAL FGFR SIGNALING IN CRANIOSYNOSTOSIS Principal Investigator & Institution: Friesel, Robert E.; Director; Maine Medical Center 22 Bramhall St Portland, Me 04102 Timing: Fiscal Year 2002; Project Start 20-SEP-1998; Project End 31-JUL-2004 Summary: Craniosynostosis, an abnormality of skull development in which the sutures of the growing calvarial bones fuse prematurely, occurs with a frequency of approximately 1 in 2500 live births. Recently, six autosomal dominant craniosynostotic syndromes, Crouzon, Jackson-Weiss, Pfeiffer, Apert, Crouzon with acanthosis nigricans and Beare-Stevenson cutis gyra were shown to be associated with mutations in either fibroblast growth factor receptor (FGFR)-l, FGFR-2 or FGFR-3. In addition, several dwarfing syndromes, achondroplasia, thanatophoric dysplasia types I and II, and hypochondroplasia were shown to be associated with mutations in FGFR-3. The FGFRs consist of a family of four high affinity transmembrane tyrosine kinase receptors. The prototype FGFR is comprised of an extracellular ligand-binding domain made up of three immunoglobulin (Ig)-like domains, a hydrophobic membrane-spanning region and a cytoplasmic tyrosine kinase domain. Mutations in the extracellular ligand-binding domain and the transmembrane domain of FGFR-1, FGFR-2 and FGFR-3 have been associated with craniosynostotic syndromes while mutations in the extracellular, transmembrane and tyrosine kinase domains of FGFR-3 have been associated with dwarfing syndromes. Our recent studies indicate that mutations in the extracellular, transmembrane and tyrosine kinase domains that are associated with craniosynostosis and other skeletal dysplasias result in ligand-independent constitutive activation of the mutant receptors. The central hypothesis of this application is that point mutations in

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FGFRs that are associated with craniosynostosis and other skeletal dysplasias result in constitutive activation of these receptors and that these receptors have altered signal transduction capabilities compared to their wild-type counterparts. This altered signaling capacity may in part be responsible for the phenotypic manifestations of these mutations. Accordingly, the specific aims of the proposal are: 1) to determine whether additional mutations identified in FGFRs that are associated with skeletal dysplasias result in constitutive receptor activation; 2) to determine whether these different mutations impart the mutant receptors with altered signal transduction properties, and 3) to determine whether constitutively activating mutations in FGFRs result in altered stability or intracellular trafficking. Together, these studies should begin to elucidate the role of mutant FGFRs in the pathogenesis of craniosynostotic conditions, as well as the role of FGFRs in normal bone growth and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FGF SIGNALING IN BONE GROWTH AND DEVELOPMENT Principal Investigator & Institution: Ornitz, David M.; Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002 Summary: Fibroblast growth factors (FGFs) are essential molecules for mammalian development. Several human genetic diseases have been identified that are caused by point mutations in the genes encoding FGF receptors (FGFRs), 1, 2 and 3. These disorders result in craniofacial and skeletal dysplasias (craniosynostosis syndromes) and chondrodysplasia syndromes and demonstrate that FGF signaling pathways are essential regulators of chondrogenesis and osteogenesis. FGFR is expressed in proliferating and proliferating and pre-hypertrophic chrondrocytes. FGFR1 is expressed in hypertrophic chrondrocytes in an adjacent domain to that of FGFR3. FGFR2 is expressed in mesenchymal condensations, the perichondrium and in the osteoblast compartment of developing bone. These very defined and non-overlapping expression patterns suggest that different FGFRs have unique signaling properties required for different stages of bone development and/or that different FGFRs are utilized to take advantage of unique responsiveness to specific ligands. Additionally, the identity and function of the FGF ligand(s) that activate three different FGFRs throughout bone growth and development is not known. The experiments proposed here will test the hypotheses that unique signaling and unique ligand binding properties of FGFRs are essential to their function at different stages of bone development. In addressing this hypothesis we will elucidate the specific roles for FGFRs in the development of the proliferating and hypertrophic compartment of the growth plate and the perichondrium/periosteum. These studies will also provide insight into the mechanisms underlying human genetic diseases. To accomplish these goals we will specifically disrupt FGFR signaling in each compartment of developing bone versus tissue-specifically expressed cre recombinase and conditionally targeted FGFRs. To test for signaling differences versus ligand specificity differences we will expand the domain of FGFR1 expression in the growth plate to encompass that of FGFR3. Additionally objectives will be to identify physiologically relevant FGF ligands involved in chondrogenesis, cranial suture growth and perichondrium/periosteum growth and to examine the biochemical function of a mutation in FGFR2 that causes Aperts syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FGFR2 IN SKELETOGENESIS--MUTATIONAL ANALYSIS IN MICE Principal Investigator & Institution: Nah-Cederquist, Hyun-Duck; Biochemistry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Provided by Applicant) The development of the craniofacial skeleton with its interposed sutures involves a complex process, for which molecular and cellular regulatory mechanisms are not well understood. Recent genetic studies have linked various activating mutations in the fibroblast growth factor receptor 2 (FGFR2) gene to a subset of craniosynostosis syndromes, which have in common craniofacial skeletal deformities associated with the premature fusion of cranial sutures. This suggests that FGFR2 may play important roles in skeletal and sutural development. To further develop this notion, the investigators have introduced bone-targeted mFGFR2 transgene constructs, containing an activating mutation (Pro253Arg; an Apert mutation) or a dominant negative mutation, into the mouse germ line and generated several lines of transgenic mice. Initial analyses of these mice revealed that those with an activating mutation manifested some of the typical craniofacial features of craniosynostosis patients. The mice with a dominant negative mutation also displayed a variety of skeletal abnormalities, but they were distinctively different from the craniosynostosis phenotype. Based on pro- mitogenic and anti-apoptotic responses to FGF signaling in bone cells, the investigators hypothesize that an activating FGFR2 mutation promotes proliferation of osteoblasts, while suppressing apoptosis in these cells, resulting in uncontrolled bone formation and, ultimately, suture fusion. In contrast, loss of normal FGFR activities may result in reduced bone cell proliferation with an increased rate of apopotosis, culminating in dystrophic bone and wide-open sutures. To test their hypothesis, the investigators will define the skeletal and suture phenotypes of newly generated transgenic mouse lines (Aim 1), investigate how these mutations alter bone cell functions associated with osteogenesis and suture formation (Aim 2), and finally determine whether the mitogene activated protein (MAP) kinase pathway is involved in some of the altered bone cell functions induced by FGFR2 mutations (Aim 3). Data collected from this pilot study will be used to develop hypotheses to be tested in a larger research project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FORMATION

FIBRONECTIN

ANTAGONISTS

IN

CRANIAL

SUTURE

Principal Investigator & Institution: Moursi, Amr M.; Pediatric Dentistry; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Craniosynostoses are a group of congenital disorders which involve the premature fusion of one or more of the cranial sutures, causing cessation or distortion of craniofacial growth. Increased intracranial pressure is the most critical complication, often resulting in poor intellectual development as well as alterations in vision. The prevalence of these disorders is 1:1000 live births and they can occur alone, or in association with craniofacial syndromes, such as Crouzon or Apert. To allow for adequate craniofacial growth and brain development, excision of the fused suture(s) is the treatment of choice. Unfortunately, re-ossification of the excised suture is common and necessitates several surgical procedures throughout childhood. A therapeutic agent which could prevent re-ossification of the excised sutures by transiently blocking osteogenesis would be an effective adjunct to surgery. Therefore,

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this study will investigate the effect on cranial suture ossification of a novel antiosteogenic agent delivered in a collagen gel. Fibronectin (FN), an extracellular matrix molecule, has been shown to play an essential role in calvarial osteoblast osteogenesis. Anti-FN antibodies, soluble cell-binding FN fragments and anti-FN receptor antibodies are all FN antagonists which have been shown to selectively and reversibly block osteogenesis. Preliminary studies utilizing a well-characterized rat calvarial organ culture system have demonstrated that anti-FN antibodies, in particular, can inhibit cranial suture fusion. Preliminary experiments also demonstrated that the delivery system, a collagen gel vehicle, can transfer the active antibody to cranial suture sites and is retained over time. In Aim 1 we will use this novel approach to identify FN antagonists that can prevent suture fusion in rabbit calvarial organ culture. The candidate reagents will be evaluated to determine their optimal suture-perturbing influence and working concentrations prior to in vivo rabbit studies. In Aim 2 we will determine characteristics of the collagen vehicle which will enhance the retention and delivery of reagents in a normal rabbit animal model. Together, studies in Aims 1 and 2 will provide a cost-efficient and time-saving method to identify and optimize the most effective suture perturbing reagents. In Aim 3 the FN antagonist selected from studies conducted in Aims 1 and 2 will be delivered to craniosynostotic rabbits to assess its ability to prevent cranial suture re-ossification. Together, these studies will 1) produce an effective screening method for potential cranial suture-perturbing reagents, 2) provide valuable information on the biology of cranial suture formation and 3) determine the potential for therapeutic applications of FN antagonists in the treatment of craniosynostosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION MORPHOGENESIS

OF

MSX2

AND

TWIST

IN

CALVARIAL

Principal Investigator & Institution: Maxson, Robert E.; Professor; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002 Summary: This is a proposal to investigate mechanisms of cranial patterning and the pathophysiology of of craniosynostosis, a human developmental defect characterized by the premature fusion of calvarial bones. Recent findings in human genetics have demonstrated that mutations in several genes can produce craniosynostosis syndromes. We showed that an activating mutation in the homeodomain protein Msx2 causes craniosynostosis, Boston type. Several groups have demonstrated that activating mutations in FGF receptors 1-3 cause Crouzon, per, Jackson-Weiss, and Pfeiffer syndromes. Loss of function mutations in the basic HLH protein M-twist are responsible for Saethre-Chotzen syndrome. Despite the identification of specific genetic defects that cause craniosynostosis, the cellular an developmental mechanisms underlying this disorder re poorly understood. In this proposal, we focus on these unresolved issues through an investigation of the function of the Msx2 and twist genes. In this proposal, we focus on these unresolved issues through an analysis of the function of the Msx2 and twist genes. We based our proposal on several key findings. First, gain of function and loss of function phenotypes in the mouse suggest a critical and complex role for the Msx2 and twist genes in calvarial morphogenesis, and in the differentiation of calvarial osteogenic cells. Second, a variety of studies suggest that Msx and twist genes are likely to function in growth factor mediated signaling in calvarial development-Msx genes in the BMP and possibly FGF pathways, twist in the FGF pathway. Third, our preliminary data with the Kedes group suggest that the Kedes group suggest that the Msx2 and

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Craniosynostosis

twist proteins can interact physically and functionally (Project 2). These data are the foundation of our overall hypothesis that Msx2 and regulate calvarial morphogenesis through effects on specific cell populations in the calvarial plates and sutures, that these effects re mediated by BMP and FGF signaling, and that a synergistic interaction between Msx2 and twist is a key aspect of this regulation. These are our specific aims: First, we will document in greater detail now normal cranial development is altered in Msx and twist mutant mice, and we will use chimera analysis to identify the tissues in which Msx2 and twist are required for calvarial development Third, we will develop structure-function assays for Msx2 and twist in calvarial development. Third, we will develop structure-function assays for Msx2 and twist in calvarial development, and ultimately test the hypothesis that a synergistic interaction between Msx2 and twist is required for calvarial development. This work will provide fundamental information about the molecular genetics calvarial development and may explain how mutations in three different classes of genes, Msx, fgfr, and twist-produce craniosynostosis in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES INVOLVED IN EAR DEVELOPMENT Principal Investigator & Institution: Mansour, Suzanne L.; Assistant Professor; Institute of Human Genetics; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2004; Project Start 01-JUL-1993; Project End 28-FEB-2007 Summary: (provided by applicant): The main objective of this research is to determine the identities, interactions and regulation of genes that participate in the development and/or function of the mouse peripheral auditory and vestibular systems. Previously, a gene trap screening strategy was employed to identify and mutate genes expressed in or adjacent to the developing inner ear. One of the genes found in the screen, Dusp6 is expressed in otic mesenchyme and encodes a dual-specificity protein phosphate that inactivates the mitogen-activated protein kinase, ERK, a downstream effectors of Fibroblast Growth Factor (FGF) signaling. FGFs play critical roles in many aspects of otic development and Dusp6 mRNA is not only expressed in many sites of FGF signaling, including otic sites, its expression also depends on FGF signaling. Furthermore, mice that lacks Dusp6 have partially penetrate postnatal lethality associated with small size and craniosynostosis. Affected animals also have ossicle and otic capsule abnormalities. The size and cranial phenotypes are characteristic to different extents of humans and mice with dominant activating mutations in FGF receptors. Hearing impairment is variably associated with the human mutations, but has not been evaluated in the mouse models. Taken together, these data suggest the hypothesis that DUSP6 is a partially redundant negative feedback regulator of FGF signaling during the development of otic and other tissues. Three Specific Aims are proposed to test the hypothesis. First, the ontogeny and cellular basis of the otic phenotypes of Dusp6 null mutants will be characterized and the status of the inner ear will be determined. Next, expression analysis performed during the critical period for development of the Dusp6 phenotypes will be used to identify candidate FGF signaling pathways mediating those phenotypes. The otic phenotypes of mouse models of Pfeiffer (FGFR1), Apert (FGFR2) and Muenke (FGFR3) Syndromes will be compared with those of Dusp6 mutants and genetic interaction studies will be used to determine which of the FGFR signaling pathways are regulated by DUSP6. Finally, expression analysis will be used to evaluate other ERK phosphates for potential redundancy with Dusp6 and their roles in otic development will be defined genetically. As the mouse ear is very similar to that of humans, we expect that our studies will apply to human ear development and shed

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light on the genetic mechanisms, which perturbs it, leading to hearing and balance disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES INVOLVED IN SKULL SUTURE MORPHOGENESIS Principal Investigator & Institution: Liu, Yi-Hsin; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002 Summary: Craniosynostosis is a common birth defect that affects newborns (1 in 3000 live births) with manifestations of abnormal skull shape which may result in raised intracranial pressure, blockage of cerebral blood flow and airway, impaired vision and auditory functions, mental retardation and adverse psychological effects, if not corrected surgically. Both genetic and environmental factors contribute to craniosynostosis. Recently, findings implicate involvement of transcription findings, such as MSX2 and TWIST, and growth factor receptors, such as FGFR1 and involvement of transcription factors, such as MSX2 and TWIST, and growth factor receptors, such as FGFR1 and FGFR2, in several craniosynostotic syndromes. Msx2 is a member of the msh gene family. It is known to bind DNA though its homeodomain and transactivate downstream target genes, which are yet to be defined. The notion that Msx2 gene activity is critical for the normal development and maintenance of cranial sutures is supported by the Msx2 gain-of-function phenotypes in a human autosomal dominant genetic disorder of skull supported by Msx2 gain-of-function phenotypes in a human autosomal dominant genetic disorder of skull development-Boston type craniosynostosis-in our transgenic mice in which Msx2 is over- expressed. We find that Msx2 transgenic mice exhibit premature closure of calvarial sutures as a consequence of excessive bone. The precocious closure of the sagit6tal suture correlates to an increase of osteogenic progenitors in the osteogenic front. We hypothesize that the osteogenic front and the suture re critical compartments in controlling the growth of the membraneous bones in the skull. Any perturbation to the osteogenic front and/or the suture, via either genetic or epigenetic means, can result in malformation of the skull. The major objectives of this project are to: (1) investigate the effect on calvarial bone growth and suture morphogenesis as a result of Msx1 and Msx2 null mutations; (2) study the Bono Morphogenetic Protein (BMP) signaling cascade, a regulator of Msx genes, in the normal development of calvarial sutures; and (3) identify additional regulatory components involved in the morphogenesis of sutures and the formation of the osteogenic front. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC EPIDEMIOLOGY OF CRANIOSYNOSTOSIS Principal Investigator & Institution: Boyadjiev Boyd, Simeon A.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: This application proposes a training plan to develop Simeon A. Boyadjiev, M.D., into an independent clinical scientist, expert in clinical and molecular genetics and genetic epidemiology. Since October 1997, Dr. Boyadjiev is a board certified Pediatrician and as of September 1999, he is certified as a Clinical Geneticist by The American Board of Medical Genetics. The Johns Hopkins University is exceptionally well suited to serve as his training site. The training program will consist of mentored research experience, multi-disciplinary conferences, and advanced course work, leading to a Master of Public Health degree in Human Genetics and Genetic Epidemiology. Mentored research will be

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Craniosynostosis

conducted as a member of the Center for Craniofacial Development and Disorders (CCDD) under his primary mentor Prof. Ethylin Wang Jabs, M.D., member of the Institute of Genetic Medicine and Director of CCDD, and co-mentor Terri Beaty, Ph.D., Professor of Epidemiology and Director of the Human Genetics and Genetic Epidemiology program at the School of Hygiene and Public Health. Prof. Garry Cutting, M.D., Director of the DNA Diagnostic Laboratory at Johns Hopkins will serve as a comentor and direct Dr. Boyadjiev's training in Clinical Molecular Genetics during the first year of the award. The research project will be conducted through clinic-based study of patients and utilize molecular and epidemiologic methodologies. The specific aims are: 1) to characterize isolated and syndromic forms of craniosynostosis; 2) to collect a sufficient number of case-parent trios with isolated craniosynostosis in order to achieve sufficient statistical power; 3) to identify and utilize new and existing single nucleotide polymorphisms (SNP) in order to establish linkage to specific chromosomal regions; 4) to identify and test candidate genes and loci for mutations and allelic associations; 5) to identify environmental risk factors for various subtypes of craniosynostosis; and 6) to develop an efficient model that can be applied toward the analysis of genetic and nongenetic causes of craniosynostosis as well as other congenital anomalies with complex inheritance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOTYPIC CRANIOSYNOSTOSIS

AND

PHENOTYPIC

VARIABILITY

IN

Principal Investigator & Institution: Richtsmeier, Joan T.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Premature closure of the neurocranial sutures, craniosynostosis, is a relatively common bir6th defect that results in increased intracranial pressure and abnormal head shape. The condition necessitates reconstructive surgery during the first months of life and therefore represents a significant public health problem. Craniosynostosis is one of a number of clinical features in over 100 syndromes. Some of these syndromes, specifically Crouzon, Apert, Jackson-Weiss, Pfeiffer, and SaethreChotzen, exhibit similarities in craniofacial phenotypes. Craniosynostosis can also occur as an apparently isolated phenomenon. Recent reviews note that over 64 different mutations of seven genes are responsible for craniosynostosis syndromes and that a single, but highly variable mutation is responsible for a large proportion of nonsyndromic coronal synostosis. As of this writing, no specific mutations have been found to be associated with isolated sagittal or isolated metopic synostosis. The long-term goal of the proposed project is to determine the role of genes associated with craniosynostosis in producing craniofacial phenotypes. This will be done by obtaining objective, quantitative measures of the craniofacial phenotypes of the craniosynostosis syndromes named above and for isolated cases for metopic, sagittal, and coronal synostosis, and by identifying the genetic mutations present in this population. Individual phenotypic characterizations will be based on three-dimensional craniofacial image data. The quantitative, three-dimensional, craniofacial characterizations will be analyzed to determine groups of individuals defined solely on the basis of cutaneous, skeletal, and/or CNS craniofacial morphology. Any correspondence between the morphological groups and the genetic mutations present in these individuals will provide an unbiased genotype-phenotype correlation. Explanations of the craniofacial phenotypic variability within our morphological groups will be sought using additional clinical data. These data include standard demographic data, epidemiological factors

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implicated in the occurrence of some craniosynostosis conditions, and clinical evaluations of neuropsychological function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP Principal Investigator & Institution: Rawlins, Joseph T.; Biomedical Sciences; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This application proposes a graduate educational program at Baylor College of Dentistry (BCD), Texas A&M University System for Mr. Joseph T. Rawlins.This program will combine PhD studies in Biomedical Sciences with concurrent clinical training leading to a DDS. Mr. Rawlins' ultimate goal is a career in dental research and academic dentistry. His research interests are directed toward growth factor regulation of bone growth in intramembranous sutures and the premature closure of sutures (craniosynostosis). A research proposal modified by Mr. Rawlins during the initial portion of his research training is submitted. This research will address hypotheses that transforming growth factor a2 (TGF-a2) regulates cell proliferation and apoptosis within the suture and these chances are associated with suture obliteration. Specifically, the research will determine: 1) if TGF-beta2 increases cell proliferation, decreases apoptosis and Twist expression in cells that express Fgfr 2, 2) whether this is followed by decreased Fgfr2 expression and increased Fgfr1 and Runx2 expression, and 3) if TGF-beta2 can induce suture obliteration in TGF-beta2 null mice calvaria in vitro, and to determine which factors are downstream of TGF-beta2 can induce suture obiliteration in TGF- beta2 null mice calvaria in in vitro, and to determine which factors are downstream of TGF-beta2 signaling by gene arrays. Experiments will use an established calvarial system to expose suture to growth factors. These experiments will provide important new information on how growth factors interact with one another to regulate cell proliferation, differentiation, and apoptosis to maintain sutures as intramembranous bone growth sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MATERNAL, FETAL & ENVIRONMENTAL CAUSES OF BIRTH DEFECTS Principal Investigator & Institution: Mitchell, Laura E.; Professor; Biomedical Sciences; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Description) The current proposal is based on the premise that a full understanding of the genetic architecture for many birth defects will only be obtained if "higher-order" effects such as gene-environment (GxE) interactions, gene-gene (GxG) interactions and maternal genotypic effects are evaluated in concert with more traditional epidemiological and genetic risk factors. Moreover, recent advances in molecular and statistical genetics provide a foundation upon which to build studies that address the role of higher-order effects, when such effects are suggested by current understanding of a disease's etiology. The investigators propose to evaluate the role of GxE interactions, GxG interactions and maternal effects in the etiology of two groups of birth defects: neural tube defects and cranial abnormalities including craniosynostosis and nonsynostotic posterior plagiocephaly (CSINSPP). These conditions were selected from other potential candidates because current understanding of their etiologies support multiple hypotheses regarding higher-order

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Craniosynostosis

effects. Hence, for these conditions in particular, it is now feasible to begin to construct a multi- dimensional blueprint of their genetic architecture. They will use state-of- the-art genotyping methods, including high-throughput array technologies, and employ stateof-the-art statistical approaches to evaluate the role of higher- order effects in the etiology of spina bifida and CS/NSPP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Krawchuk, Dayana; Genetics and Development; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-SEP-2002 Summary: (provided by applicant) Saethre-Chotzen syndrome (SCS) is a commonly inherited disorder predisposing humans to premature fusion of the skull calvarial bones (craniosynostosis) and a variety of limb defects. Greater than 45 percent of SCS patients have loss-of-function mutations in one copy of the Twist gene, making Twist haploinsufficiency a causative factor for SCS. Mice also show haploinsufficiency for Twist, as Twist heterozygotes exhibit craniofacial defects and toe duplications. Twist is a well-conserved basic helix-loop-helix (bHLH) protein essential for embryonic development in Drosophila and mouse. Its loss-of-function phenotypes in the limbs suggest that Twist normally has important patterning functions during limb development, interestingly, published and preliminary data show that overexpression of another bHLH protein essential for limb development, HAND2, causes phenotypes resembling those seen in SCS patients and in mice haploinsufficient for Twist. Because HAND2 gain-of-function phenocopies Twist loss-of-function, we hypothesize that HAND2 and Twist interact antagonistically during limb development. We will test for a genetic interaction between the two genes using simultaneous loss-of-function and simultaneous gain-of-function assays in both mouse and chick. In addition, we will use biochemical assays to determine the molecular mechanism behind the interaction between HAND2 and Twist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR BASIS OF SAETHRE CHOTZEN SYNDROME Principal Investigator & Institution: Jabs, Ethylin W.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Craniosynostosis is characterized by premature fusion of calvarial bones, resulting in abnormal head shape. It is one of the most frequent human malformations, occurring either as an isolated abnormality or in association with other congenital anomalies. Saethre-Chotzen syndrome is a common craniosynostosis condition with autosomal dominant inheritance, high penetrance, and variable expressivity. Forty-six percent of these patients have mutations in the TWIST gene. This gene codes for a putative transcription factor with a basic helix-loop-helix motif, suggesting that it must dimerize prior to binding its DNA target. Another 22% of patients have fibroblast Growth Factor Receptor (FGFR) mutations. In Drosophila, twist is an upstream regulator of DFR1, a homologue of FGFR. These data suggest that TWIST and FGFR may be components of a conserved, molecular pathway implicated in cranial development. Mutation of other genes involved in this pathway may also cause craniosynostosis. The goal of this proposal is to study the molecular pathogenesis of craniosynostosis, and in particular, Saethre-Chotzen syndrome. The specific aims are to:

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1) identify mutations in the other 32% of Saethre-Chotzen syndrom patients by screening candidate genes presumed to be involved in the same molecular pathway (e.g., FRS2, SNAIL); 2) identify mutations in candidate genes (e.g., BARX2) for other non-syndromic and syndromic craniosynostosis conditions, such as metopic synostosis; 3) determine the mechanism(s) of the haploinsufficiency of TWIST mutations in SaethreChotzen syndrome patients by assaying for reduction of TWIST transcription of protein levels, dimerization, or DNA binding; 4) determine in Saethre-Chotzen syndrome patients, the effect of TWIST mutations on the level of expression of other candidate genes of the molecular pathway. Those affected would be downstream of TWIST, while those not affected may be upstream components; and 5) determine the gene mutated in a rabbit model of coronal synostosis which may proven to be a useful system to further delineate the molecular pathway of craniosynostosis which may prove to be a useful system to further delineate the molecular pathway of craniosynostosis. These studies may identify additional craniosynostosis loci and provide insight into the molecular pathways involved in development of the skull. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ETIOLOGY OF CRANIOSYNOSTOSIS SYNDROME Principal Investigator & Institution: Gripp, Karen; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR GENETICS OF A SYNDROME WITH HEARING IMPAIRMENT Principal Investigator & Institution: Post, J Christopher.; Director; Allegheny-Singer Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 30-JUN-2005 Summary: This revised application is a continuation of R29 DC02398, "Genetic Mapping of a Syndrome with Hearing Impairment." Our research has focused on the molecular basis of craniofacial disorders, in particular Crouzon craniofacial dysostosis (CFD), which is characterized by craniosynostosis (premature closure of calvarial sutures) and mapping CFD and delineating the entire structure of the mutated gene, FGFR2. We determined that a single point mutant osteoblasts. Based upon these observations, we now hypothesize that the default pattern of tissue growth, when two like tissues come into proximity, is fusion. The normal development of the calvarium (which requires like tissues not to fuse) would then be dependent on complex genetic systems to override the natural fusion process, perhaps by increasing sutural apoptotic rates. Craniosynostosis would result from a reversion to the default (fusion) pathway of tissue growth. Thus, constitutive signaling from mutated FGF4s causes a dominant gain of function initiating involved. Newly developed nucleic acid array technologies permit the comprehensive evaluation of the entire set of expressed genes (the expressome) throughout the course of abnormal suture development. Thus, for this new proposal, we devised a chimeric nude rat model, which when implanted with mutant human osteoblasts beneath the calvarium, develops premature synostosis. The differential gene expression patterns between samples from this novel in vivo model, related in vitro cell co- cultures, and controls will be analyzed across time to identify the downstream genes involved in craniosynostosis. Laboratory techniques for analyzing samples will include differential

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Craniosynostosis

display and robotically gridded nucleic acid arrays. Gene analysis will be prioritized based upon homology to genes known to control multicellular tissue growth, cell contact and adhesion, and osteoblasts processes active in craniosynostosis. Finally, the differentially expressed genes will be related to the biology of cranial development by 1) in situ hybridization for analysis of spatial and temporal patterns; and 2) evaluation of impact on apoptosis for assessment of physiological effect. The delineation of the panoply of genes involved in causing craniosynostosis will enhance our understanding of these diseases and suggest new therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF CRANIAL SUTURE FUSION Principal Investigator & Institution: Longaker, Michael T.; Professor of Surgery; Surgery; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-APR-1999; Project End 30-JUN-2008 Summary: (provided by applicant): This application seeks to understand the biology regulating physiologic and pathologic cranial suture fusion to facilitate the development of therapies to treat human craniosynostosis. With an incidence of 1:2000 world-wide, craniosynostosis represents a significant biomedical burden. Children with craniosynostosis require complex reconstructive surgery associated with significant morbidity. We will study the molecular and cell biology regulating fusion of cranial sutures in mice. In the first part of our application will use microarray analysis to identify differences in the genomic blueprints of regionally differentiated dura from patent and fusing sutures of mice. The data derived from these studies will be used to identify genes that are candidates for regulators of cranial suture and osteoblast biology, and will be further tested in our coculture model to establish their functional role in suture biology. The second part of our application will study the effects of regional dura mater, the primary regulator of suture fusion or patency, on osteoblast biology using a novel dura mater-osteoblast co-culture system. This system will enable us to manipulate the signaling between dura mater and calvarial osteoblasts to determine the paracrine mechanisms mediating suture fate. The third part of this application will determine how FGF signaling regulates suture fusion. We will manipulate the biology of FGF-2 ligand and FGF-R2 null mutants both in cell culture and in vivo in order to determine the mechanism(s) of FGF mediated suture fusion. In the fourth part of this application we will investigate the function of Noggin, a BMP antagonist capable of maintaining suture patency. We will use Noggin null mutants, and Noggin antisense adenovirus, to determine whether Noggin is required to maintain embryonic and post-natal suture patency, respectively. We will then use a double transgenic mouse (FGFR1 / NogginLacZ ) to examine the effects of increased FGF signaling on Noggin expression in a pathologically fusing suture. Finally, pathologically fusing sutures will be rescued with perinatal gene therapy using a Noggin adenovirus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEL-2 GENE IN BONE FORMATION & CRANIAL SUTURE CLOSURES Principal Investigator & Institution: Ting, Kang; Orthodontics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The applicant proposes to investigate the function of NEL-2, a novel gene isolated in craniosynostosis (CS), in bone formation and premature suture closure. CS,

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which affects roughly one of every 3,000 infants, is the premature obliteration of cranial sutures in association with cranial dysmorphism. We have isolated and identified cDNA whose expression is upregulated in the premature suture fusion sites of patients with a prevalent type of CS, non-familial unilateral coronal synostosis (UCS). The nucleotide sequence of the full length cDNA of this gene has approximately 61 percent homology with the chicken nel gene, and thus has been named this cDNA human NEL-2. Both chicken nel and human NEL-2 consist of 6 EGF-like repeats. We demonstrated that the human NEL-2 messages are primarily localized in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins and within the condensing mesenchymal cells of the newly formed bone. Human NEL-2 is specifically expressed in fetal brain but not in fetal lung, kidney or liver. We have also shown that rat NEL-2 is expressed in rat calvarial osteoprogenitor cells and is largely absent in rat tibia and fibroblast cell culture. Mammalian expression vectors expressing rat NEL-2 were constructed and transfected into MC3T3 cell line. An approximate two and a halffold increase in mineralization was seen as compared to the control. In addition, overexpression of rat NEL-2 induced BMP-2 gene expression. Our data suggest that the NEL-2 gene is preferentially expressed in cranial intramembranous bone and neural tissue, and it may be associated with membranous bone formation. Therefore, we hypothesize that the overexpression of the NEL-2 gene product induces the overproduction of cranial membranous bone. In addition premature cranial suture closure, as seen in craniosynostosis (CS) and non-familial unilateral coronal synostosis (UCS), may be due to the overproduction of cranial membranous bone and the overexpression of NEL-2. To test this hypothesis, we propose the following specific aims: 1) Determining expression of NEL-2 in osteoblasts of non-familial UCS patients and at different stages of bone formation in vitro; 2) Determining the effect of NEL-2 on bone formation in vitro; 3) Determining the effect of NEL-2 on bone formation in human calvaria osteoblastic cells from CS patients; 4) Characterizing the regulation of NEL-2 expression; and 5) investigating the overexpression effect of NEL-2 on the rat cranial suture closure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBEHAVIORAL CORRELATES OF CRANIOSYNOSTOSIS Principal Investigator & Institution: Speltz, Matthew L.; Professor; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: In this multi-site, 5-year longitudinal study, infants with one of four types of single-suture craniosynostosis will be recruited: sagittal, metopic, right unilateral coronal, and left unilateral coronal (n=258). A case-matched "control" group of healthy, normal infants (n=285) will also be followed. The long-term objectives are to chart the neurobehavioral course of single-suture fusions and to better understand how the developing cranium affects human brain growth and function. Specific aims are to: (1) Clarify the neurobehavioral development and parental adjustment of infants with and without single-suture fusions at three time points in infancy and early childhood (just prior to cranioplastic surgery and twice post-surgery, at 18 and 36 months of age); (2) Among children with craniosynostosis, clarify relations between neurobehavioral development and abnormality in bone and brain tissue as indicated by measures taken pre-surgery CT scans; (3) Among children with unicoronal synostosis, clarify relations between neurobehavioral development and presence of genetic mutations; (4) Develop predictive models of 36-month outcomes for infants with craniosynostosis; and (5) Determine the relation between age of cranioplastic surgery and pre- and post- surgery

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neurobehavioral development. This research will take place in medical centers located in Seattle, Chicago, St. Louis and Atlanta. Seattle's Children's Hospital and Regional Medical Center is the lead agency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NICOTINIC DEVELOPMENT

ACETYLCHOLINE RECEPTORS

&

NEURONAL

Principal Investigator & Institution: Pugh, Phyllis C.; Anatomy and Neurobiology; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Nicotine, as consumed through tobacco use, is a drug abused by nearly 47 million Americans. Understanding the consequences of nicotine exposure is therefore a major health issue in the United States and of interest at epidemiological, clinical and basic science levels. Of particular concern are the approximately 20% of women who smoke, two-thirds of whom continue to do so during pregnancy. Epidemiological studies link maternal smoking to low infant birthweight, reduced head size, congenital heart defects, isolated craniosynostosis, craniofacial anomalies, and limb malformations. As nicotine is a major toxic component of tobacco smoke and is present at equivalent levels in fetal and maternal tissues, it is strongly implicated as a causative agent of such defects. The physiological effects of nicotine are exerted by activation of nicotinic acetylcholine receptors (AChRs). AChRs are pentameric, ligand-gated ion channels, ubiquitously expressed in both the central and peripheral nervous systems, as well as in skeletal muscle. Thus, in addition to the established functions of AChRs in signaling, addiction, task attention, and neurological disease, AChRs are also likely to participate in smoking-related birth defects. The ability of nicotine to cause such defects is consistent with the appearance of AChRs in neuronal precursors and in the human CNS prior to cortical development. The early appearance of AChRs and their known ability to influence neuronal survival and process outgrowth directly implicate them in normal neuronal development in vivo. At present, however, developmental roles for AChRs are novel and remain poorly understood. This proposal will analyze the developmental significance of neuronal AChRs using the embryonic chick ciliary ganglion (CG) as a model system. CG neurons are ideally suited for such studies because they express well-defined AChR types having distinct properties and unique functions. Moreover, the CG is accessible to manipulation throughout development, both in vivo and in cell culture. A major AChR type is sensitive to blockade by (-bungarotoxin ((Bgt). The investigator has previously shown that these (Bgt-AChRs influence process outgrowth and promote neuronal survival in culture. Further, preliminary studies suggest that (Bgt-AChRs can influence synapse formation on CG neurons in culture. The experiments described here will extend these findings to the in vivo setting using retroviral delivery of mutated AChR genes into embryos during neuronal development. These alterations will be assessed for their impact on neuronal survival (Aim 1), synapse formation (Aim 2), and AChR distribution (Aim 3). The proposed studies are expected to provide new information concerning the developmental significance of AChRs in vivo. Fulfilling the goals of this project will aid in developing the investigator's scientific independence and is expected to reveal additional clues for understanding how nicotine abuse contributes to birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POSTOPERATIVE CYTOKINE THERAPY OF CRANIOSYNOSTOSIS Principal Investigator & Institution: Mooney, Mark P.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: The surgical management of coronal suture synostosis routinely involves the early extirpation of the synostosed coronal suture while brain mass growth is still rapid. Frequently, however, the suturectomy sites show rapid and extensive hyperstosis and eventual resynostosis. This refusion further restricts the growing brain, increases intracranial pressure, alters craniofacial growth, and requires additional and extensive surgical procedure to correct the subsequent problem which increases patient morbidity and mortality. Recent studies have shown that developmental changes in the expression of the carious transforming Growth Factor-beta (TGF- beta) isoforms are responsible, in part, for normal cranial vault suture formation, maintenance, and eventual fusion. Overexpression of TGF-beta1 has also been noted in humans and rabbits with familial, nonsyndromic craniosynostosis, and has been implicated in the production of hyperostosis, leading to synostosis of the cranial vault sutures. Perinatal treatment that interferes with TGF-beta1 production and/or function may prevent post-surgical resynostosis, decrease intracranial pressure, improve craniofacial growth, and obviate multiple surgeries in the clinical management of neonates with various synostotic conditions. The present proposal is designed to test this hypothesis in a unique rabbit model of human familial, non-syndromic craniosynostosis. The proposed research will: 1) surgically extirpate the synostosed coronal suture in 40, 10 day old New Zealand White rabbits with familial, non-syndromic craniosynostosis; 2) treat the suturectomy site in ten synostosed rabbits with either a) anti-TGF-beta1 in a slow release (35 day) collagen past vehicle, b) antiIggamma in a slow release (35 day) collagen paste, which will serve as the antibody control group, c) the slow release (35 day) collagen paste vehicle only, which will serve as the vehicle control group, or d) leave the remaining ten synostosed rabbits with suturectomy untreated which will serve as the sham control group; 3) quantitatively assess intracranial pressure, cranial vault growth, coronal suturectomy site bone volume, intracranial volume, brain morphology, and cranial vault shape at 10, 25, 42 and 84 days of age using serial head radiographs and 3-D CT scan reconstructions; and 4) harvest the suturectomy sites from each group at 42 and 84 days of age for histological examination and quantify the extent of coronal suturectomy site resynostosis following the various experimental manipulations using histomorphometry from serial histological preparations. The ultimate goal of this study is to provide a biological basis for future cytokine therapy protocols designed to manipulate postoperative suturectomy site reossification, decrease intracranial pressure, and ameliorate craniofacial growth deformities in human infants with familial, nonsyndromic craniosynostosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RAMAN IMAGING OF BONE TISSUE MINERALIZATION Principal Investigator & Institution: Morris, Michael D.; Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 10-JAN-2003; Project End 30-NOV-2006 Summary: (provided by applicant): Bone is a complex system consisting of a carbonated apatitic calcium phosphate phase supported on a collagen-rich extracellular matrix. While the macroscopic properties of bone have been extensively investigated using

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Craniosynostosis

different techniques in various biological systems, the early steps in bone tissue mineralization are not well understood. In an effort to characterize bone growth, numerous studies have been conducted to understand the chemical mechanisms involved in both de novo bone formation and bone remodeling. Despite this increased interest, an understanding of the processes governing early mineralization of bone is still incomplete. This proposal will use near-infrared Raman microspectroscopy and Raman imaging to study early mineralization in the mouse calvaria (the flat bones that comprise the top of the skull). The goal is to understand the steps leading to the deposition of new mineral and the chemical and physical transformations that the mineral undergoes during fetal and early postnatal development. Because Raman microspectroscopy is a relatively new tool in bone research, the work will begin with validation of protocols for Raman spectroscopy of bone tissue. The effects of standard specimen fLxing and embedding protocols and the potential Raman or fluorescence interference from a set of common histological stains will be examined. It is proposed that there will be few or no problems encountered beyond the known effects, such as protein cross-linking, of certain fixing protocols. If interferences due to the staining protocols occur, multivariate spectral and image processing will be used to overcome them. Because the progress of mineralization is accompanied by shifts in mineral spectral bands, the interpretation of small spectral band shifts will be put on a fawn foundation. In a subcontract to Central Michigan University, vibrational spectra (band positions and frequencies) of substituted hydroxyapatites will be computed by density functional theory and compared to Raman spectral measurements of model compounds (synthetic non-substituted and substituted hydroxyapatites) and on murine calvarial bone tissue. Systematic Raman imaging will be performed on calvarial sections harvested from normal mice just prior to the onset of mineralization (fetal day 15.5) until postnatal day 14. Raman imaging will be carried out at 1-day intervals during the prenatal period and at 2-day intervals during the postnatal period. Correlative immunohistological staining and Raman imaging will be used to understand the effects of bone sialoprotein and osteocalcin on the course of mineralization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CBFAL FUNCTION BY TWIST Principal Investigator & Institution: Karsenty, Gerard; Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 30-JUN-2007 Summary: (provided by applicant) The transcriptional mechanisms regulating osteoblast differentiation are not yet fully understood despite the identification of Cbfa1 as a gene necessary and sufficient for this process. Specifically, one critical question that has not been solved yet is to understand the reason for the long delay (3 days) between the onset of Cbfa1 expression during development and the appearance of the first osteoblasts. One possible molecular mechanism to account for this delay would be that a transcriptional inhibitor of osteoblast differentiation may be coexpressed with Cbfa1 transiently during the early stage of skeletal development. We have accumulated genetic and molecular evidence that Twist, a BFILH containing transcription factor acts as a transcriptional and specific inhibitor of Cbfa1. To address this hypothesis we propose to use in this application biochemical, molecular biology and genetic approaches. We believe that these studies will improve our understanding of osteoblast differentiation and early skeleton development. The specific aims are: To perform systematic deletion mutation and domain swapping analyses of Twist to define the domain responsible for its antiosteogenic function. To overexpress either wild-type or mutated forms of Twist

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during development to delay osteoblast differentiation in vivo. To generate an osteoblast-specific deletion of Twist to initiate osteoblast differentiation earlier during development. To perform biochemical assays to elucidate the molecular bases of the Cbfa 1/Twist interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CRANIAL SUTURE DEVELOPMENT BY TGF AND FGF Principal Investigator & Institution: Gosain, Arun K.; Surgery; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2003; Project Start 10-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Craniosynostosis is a significant health issue in humans, yet the pathogenesis and the mechanism of craniosynostosis are still unsolved. Clinical and experimental studies have implicated Transforming Growth Factor-a 1 (TGF-beta1) and Fibroblast Growth Factor-2 in cranial suture fusion. There is evidence that the effect of one or both molecules on suture fusion may be further altered by noggin, a bone morphogenetic protein antagonist. Gain of function mutations in FGF receptors have been reported in numerous human craniosynostosis syndromes, with the majority of these syndromes implicating FGF receptors 2 (FGFR2). However, the precise role of TGF-beta1 and FGF-2 in cranial suture development has not been explained. We hypothesize that 1) during the period of posterior frontal (PF) suture development in the mouse, altered biologic activity of TGF-beta1 and FGF-2 regulates fusion of the overlying suture calvaria, and 2) expression of these molecules in the fused PF suture in mice parallels that in fused sutures from human children with congenital craniosynostosis. Alteration in FGFR2 and noggin may also contribute to alter biologic activity of TGF-Beta1 and FGF-2 and further regulate suture fusion. Specific aims are 1) To quantity gene expression of TGF-beta1, FGF-2, FGFR2, and noggin in mouse cranial tissues harvested from both in vivo and in vitro models. Additionally, protein levels of TGF- beta1, FDF-2, and noggin will be measured in culture media in vitro using ELISA. 2) To quantitate gene expression of these same growth factors and receptors harvested from human patients with cogenital craniosynostosis. We will harvest tissue from both a fused suture and a patent suture from children undergoing craniotomy as part of the standard treatment for craniosynotosis. These data will be used to help determine the relationship between the mouse and human cranial suture systems. 3) To modulate cranial suture fusion in the mouse model, in vitro by modulating the bioavailability of the growth factor and receptors described in Aim 1. We will add recombinant forms of each molecule or antibodies to these molecules to either induce fusion of the normally patent sagittal suture or block the normal fusion of the PF suture. 4) To investigate the possibility of in vitro plasmid DNA transfection of mouse cranial tissue. If successful, gene manipulation of the target growth factors and receptors may be used to regulate cranial suture development in future studies. 5) To gain adequate knowledge of molecular biology to develop into an independent clinician-scientist. This proposal will provide mechanistic insights into the regulation of cranial suture development, and help to relate mouse and human models of craniosynostosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF FGF SIGNALING IN BONE DEVELOPMENT Principal Investigator & Institution: Basilico, Claudio; Professor and Chairman; Microbiology; New York University School of Medicine 550 1St Ave New York, Ny 10016

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Craniosynostosis

Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-DEC-2005 Summary: Skeletal morphogenesis is controlled by a network of signaling molecules that first determine the fate of undifferentiated stem cells of the mesenchymal lineage and then regulate the proliferation and differentiation of committed osteogenic cells. Among the signaling molecules which influence bone morphogenesis, fibroblast growth factors (FGF) and their cognate receptors (FGFR) have been recently shown to play a major role both in endochondral and intramembranous bone formation. Activating mutations in FGFR3 have been shown to be responsible for several genetic forms of human dwarfism, and other activating mutations in FGFR1, FGFR2 and FGFR3 have been linked to many craniosynostosis syndromes. Mouse genetic experiments have confirmed that unregulated FGF signaling causes bone malformations and suggested that FGFs may act as negative regulators of bone growth. However, the molecular mechanisms through which FGFs influence the proliferation of differentiation of osteogenic cells (e.g. chondrocytes and osteoblasts) remain to be elucidated. The goal of this research project is to study the response to FGF signaling of chondrocytes. We have shown that FGF treatment inhibits the proliferation of chondrocytes, and that this inhibition requires activation of the STAT-1 pathway. Using organ cultures of metatarsal bones rudiments of E15 murine embryos we have also shown that FGFs regulate chondrocyte proliferation and bone development and that this effect also requires STAT-1. We wish to understand the molecular mechanisms underlying the growth inhibitory response of chondrocytes to FGF signaling and how FGF signaling affects chondrocyte proliferation and differentiation. We will study 1) the signal transduction pathways activated by FGF receptors in chondrocytes with an emphasis on the mechanisms leading to activation on STAT-1, which plays an essential role in the chondrocyte response to FGF; 2) how the progress of the differentiation program which takes place during organ culture of bone rudiments from murine embryos is affected by FGF treatment or by molecules in the FGF signaling pathways; 3) the effect of modulating FGF signaling on bone morphogenesis in vivo, using transgenic and knockout mice, to verify how STAT-1 influences long bone development and chondrodysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SKI-REGULATED NETWORKS IN FACIAL AND SKULL DEFECTS Principal Investigator & Institution: Colmenares, Clemencia; Associate Staff; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Craniofacial defects are among the most common human malformations. We have developed a mouse model of facial clefting and defective cranial bone suture closure by generating a knockout of the Ski gene. The craniofacial abnormalities in Ski-null mice correctly predicted the involvement of human Ski in 1p36 deletion syndrome, a human disorder that includes open fontanelles and a low incidence of facial clefting among its diverse features. The incidence of clefting in Ski -null mice is strain-specific, and in mixed backgrounds is determined by a small number of modifier genes. We will use the strain dependent model of facial clefting to identify polymorphisms in modifier loci by their association with clefting in the C57BL/6J strain, but not in 129 mice that do not exhibit facial clefting. Modifiers of this type are likely to be involved in clefting in 1p36 patients, and may be involved in common forms of clefting which are influenced by multiple genes. Mechanistic studies will focus on Ski as a co-regulator of transcription related to the BMP pathway because the BMP-regulated genes, Msx-1, Msx-2 and Cbfa1 play critical roles in craniofacial

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development, and have been implicated in many facial and cranial disorders similar to those resulting from the loss of Ski. We will also search for genes in the affected craniofacial regions that are deregulated in the absence of Ski using microarray technology. Genes identified in this way are likely to play a role in these defects in mice and will make excellent candidates for genes likely to be involved in human craniofacial abnormalities. We propose to identify polymorphisms in the non-deleted allele of human Ski because loss of function mutations of that allele may underlie susceptibility to facial clefting and other defects in 1p36 patients. Finally, we will generate Ski transgenic mice to determine whether they reproduce the craniosynostosis phenotype resulting from a duplication of the Ski locus in humans. These studies will contribute to our understanding of the gene regulatory networks that control craniofacial development, and of how disruption of these networks result in craniofacial defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SNP DISCOVERY AND ANALYSIS IN CRANIOFACIAL BIRTH DEFECTS Principal Investigator & Institution: Scott, Alan F.; Director; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: (Adapted from the Applicant's Description): This application proposes to locate single nucleotide polymorphisms SNPs using high throughput sequencing of genomic PCR products amplified from genes with demonstrated or presumed relevance to human birth defects. High throughput screening for this panel of SNPs will be applied first to a well characterized set of parent- offspring trios ascertained through a case with non-syndromic oral-facial clefts (OFC), including cleft lip with or without cleft palate (CLIP) and cleft palate (CP) using a high-throughput screening process, and second to patients with non-syndromic craniosynostosis. These case-parent trios are drawn from separate studies of oral clefts or craniosynostosis designed to identify genes involved in the etiology of this common group of birth defects and test for possible interaction with environmental exposures. The case- parent trio design proposed here tests for linkage in the presence of linkage disequilibrium, and the availability of these DNA samples on a large number of case-parent trios will allow immediate tests for the SNP markers developed as part of this proposal. Following the OFC study the investigators will extend SNP screening to a collection of craniosynostosis patients and their parents from a previous study conducted by the investigators and from the Centers of Birth Defect Research and Prevention sponsored by the Centers for Disease Control (CDC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT

TRANSCRIPTIONAL

REGULATION

OF

MESODERM

Principal Investigator & Institution: Corsi, Ann K.; Biology; Catholic University of America 620 Michigan Ave Ne Washington, Dc 20064 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-DEC-2005 Summary: (provided by applicant) The research goal is to elucidate a transcriptional cascade involved in mesodermal patterning and development in the nematode Caenorhabditis elegans. The hypothesis that two basic helix-loop-helix transcription factors, CeTwist and CeE/DA, together activate target genes that affect mesodermal fate and function will be tested. Specific Aim 1 will investigate the genetic interactions of

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CeTwist, CeE/DA, and unknown proteins at target promoters by performing a genetic screen designed to find suppressors of a special allele of the CeTwist gene. In Specific Aim 2, DNA microarrays will be hybridized with RNA made from animals overexpressing CeTwist and CeEDA to identify downstream target genes which will be subsequently characterized. These studies are medically relevant because individuals with mutations in the human Twist gene are afflicted with Saethre-Chotzen syndrome. This syndrome is characterized by the premature fusion of cranial sutures called craniosynostosis. Similar defects are found in other syndromes associated with downstream Twist target genes that have homologs in C elegans. Out of about 100 related forms of craniosynostosis, 30 are thought to arise from single gene disorders, and a specific gene has been identified in less than 10 disorders. New genes in the pathway that are identified in C elegans are predicted to be good candidates for the unknown genetic basis underlying these human disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

A 19-week-old fetus with craniosynostosis, renal agenesis and gastroschisis: case report and differential diagnosis. Author(s): Sergi C, Stein H, Heep JG, Otto HF. Source: Pathology, Research and Practice. 1997; 193(8): 579-85; Discussion 587-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9406252

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A case of I-cell disease (mucolipidosis II) presenting with craniosynostosis. Author(s): Aynaci FM, Cakir E, Aynaci O. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2002 December; 18(12): 707-11. Epub 2002 October 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483356

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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 comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. Author(s): Johnson D, Horsley SW, Moloney DM, Oldridge M, Twigg SR, Walsh S, Barrow M, Njolstad PR, Kunz J, Ashworth GJ, Wall SA, Kearney L, Wilkie AO. Source: American Journal of Human Genetics. 1998 November; 63(5): 1282-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9792856

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A comprehensive screen of genes implicated in craniosynostosis. Author(s): Johnson D. Source: Annals of the Royal College of Surgeons of England. 2003 November; 85(6): 3717. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629875

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A craniometric study of bicoronal craniosynostosis (BCC). Author(s): Slomic AM, Bernier JP, Morissette J, Renier D. Source: Journal of Craniofacial Genetics and Developmental Biology. 1992 JulySeptember; 12(3): 174-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1517397

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A craniometric study of sagittal craniosynostosis (SC). Author(s): Slomic AM, Bernier JP, Morissette J, Renier D. Source: Journal of Craniofacial Genetics and Developmental Biology. 1992 JanuaryMarch; 12(1): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1572941

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A distinct autosomal dominant craniosynostosis-brachydactyly syndrome. Author(s): Glass IA, Chapman S, Hockley AD. Source: Clinical Dysmorphology. 1994 July; 3(3): 215-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981856

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A longitudinal, statistical study of reoperation rates in craniosynostosis. Author(s): Williams JK, Cohen SR, Burstein FD, Hudgins R, Boydston W, Simms C. Source: Plastic and Reconstructive Surgery. 1997 August; 100(2): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9252595

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A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis. Author(s): Jabs EW, Muller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB, et al. Source: Cell. 1993 November 5; 75(3): 443-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8106171

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A novel mutation, Ala315Ser, in FGFR2: a gene-environment interaction leading to craniosynostosis? Author(s): Johnson D, Wall SA, Mann S, Wilkie AO. Source: European Journal of Human Genetics : Ejhg. 2000 August; 8(8): 571-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10951518

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A plea for early operation for craniosynostosis. Author(s): Shillito J Jr. Source: Surgical Neurology. 1992 March; 37(3): 182-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1536022

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A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals. Author(s): Elanko N, Sibbring JS, Metcalfe KA, Clayton-Smith J, Donnai D, Temple IK, Wall SA, Wilkie AO. Source: Human Mutation. 2001 December; 18(6): 535-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748846

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A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) causes non-syndromic craniosynostosis. Author(s): Tsai FJ, Wu JY, Lee CC, Tsa CH. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 June; 89(6): 672-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914960

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A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome. Author(s): Muenke M, Gripp KW, McDonald-McGinn DM, Gaudenz K, Whitaker LA, Bartlett SP, Markowitz RI, Robin NH, Nwokoro N, Mulvihill JJ, Losken HW, Mulliken JB, Guttmacher AE, Wilroy RS, Clarke LA, Hollway G, Ades LC, Haan EA, Mulley JC, Cohen MM Jr, Bellus GA, Francomano CA, Moloney DM, Wall SA, Wilkie AO, et al. Source: American Journal of Human Genetics. 1997 March; 60(3): 555-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9042914

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A variant of Fine-Lubinsky syndrome: a Japanese boy with profound deafness, cataracts, mental retardation, and brachycephaly without craniosynostosis. Author(s): Nakane T, Mizobe N, Hayashibe H, Nakazawa S. Source: Clinical Dysmorphology. 2002 July; 11(3): 195-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072800

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Absence of multiple extraocular muscles in craniosynostosis. Author(s): Greenberg MF, Pollard ZF. Source: Journal of Aapos : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus. 1998 October; 2(5): 307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10646755

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Absent fibula and craniosynostosis: a 25 year follow up. Author(s): Lowry RB. Source: Journal of Medical Genetics. 1993 May; 30(5): 445-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8100584

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Advancement-onlay: an improved technique of fronto-orbital remodeling in craniosynostosis. Author(s): Cohen SR, Kawamoto HK Jr, Burstein F, Peacock WJ. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1991 September; 7(5): 264-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1933927

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Advances in craniosynostosis research and management. Author(s): Guimaraes-Ferreira J, Miguens J, Lauritzen C. Source: Adv Tech Stand Neurosurg. 2004; 29: 23-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15035336

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Airway obstruction in severe syndromic craniosynostosis. Author(s): Lo LJ, Chen YR. Source: Annals of Plastic Surgery. 1999 September; 43(3): 258-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10490176

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Akinesia, arthrogryposis, craniosynostosis: a presentation of neonatal myasthenia with fetal onset. Author(s): Cantagrel S, Maury L, Yamamoto AM, Maheut J, Toutain A, Castelnau P. Source: American Journal of Perinatology. 2002 August; 19(6): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357420

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Analysis of patients with craniosynostosis syndromes for a pro246Arg mutation of FGFR4. Author(s): Gaudenz K, Roessler E, Vainikka S, Alitalo K, Muenke M. Source: Molecular Genetics and Metabolism. 1998 May; 64(1): 76-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9682222

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Anomalous medial rectus muscle insertion in a child with craniosynostosis. Author(s): Coats DK, Ou R. Source: Binocul Vis Strabismus Q. 2001 Summer; 16(2): 119-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388885

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Anomalous venous drainage in a case of non-syndromic craniosynostosis. Author(s): Anderson PJ, Harkness WJ, Taylor W, Jones BM, Hayward RD. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1997 February; 13(2): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9105746

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Are routine preoperative CT scans necessary in the management of single suture craniosynostosis? Author(s): Cerovac S, Neil-Dwyer JG, Rich P, Jones BM, Hayward RD. Source: British Journal of Neurosurgery. 2002 August; 16(4): 348-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12389887

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Assessment and treatment of craniosynostosis. Author(s): Thompson D, Jones B, Hayward R, Harkness W. Source: Br J Hosp Med. 1994 June 15-July 12; 52(1): 17-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7952760

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Assessment of continuous intracranial pressure recordings in childhood craniosynostosis. Author(s): Eide PK, Helseth E, Due-Tonnessen B, Lundar T. Source: Pediatric Neurosurgery. 2002 December; 37(6): 310-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422046

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Assessment of extraocular muscles position and anatomy by 3-dimensional ultrasonography: a trial in craniosynostosis patients. Author(s): Somani S, Mackeen LD, Morad Y, Buncic JR, Armstrong DC, Phillips JH, Levin AV. Source: Journal of Aapos : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus. 2003 February; 7(1): 54-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12690371

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Assignment of a gene locus involved in craniosynostosis to chromosome 5qter. Author(s): Muller U, Warman ML, Mulliken JB, Weber JL. Source: Human Molecular Genetics. 1993 February; 2(2): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8499900

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Autosomal dominant holocalvarial craniosynostosis. Author(s): Pillar G, Zaaroor M, Gershoni-Baruch R. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1995 November; 11(11): 617-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8608575

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Baller-Gerold syndrome craniosynostosis-radial aplasia syndrome. Author(s): Anyane-Yeboa K, Gunning L, Bloom AD. Source: Clinical Genetics. 1980 February; 17(2): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7363501

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Baller-Gerold syndrome: an 11th case of craniosynostosis and radial aplasia. Author(s): Boudreaux JM, Colon MA, Lorusso GD, Parro EA, Pelias MZ. Source: American Journal of Medical Genetics. 1990 December; 37(4): 447-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2260585

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Barrel stave osteotomy for correction of turribrachycephaly craniosynostosis deformity. Author(s): Persing JA, Edgerton MT, Park TS, Jane JA. Source: Annals of Plastic Surgery. 1987 June; 18(6): 488-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3605983

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Bilateral coronal and right lambdoidal craniosynostosis. Case report and review of the literature. Author(s): Weiss SR, Raskind R. Source: Int Surg. 1969 September; 52(3): 215-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5804093

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Bilateral flap operation for craniosynostosis. Author(s): Samra KA, Sorour O. Source: Journal of Neurosurgery. 1968 December; 29(6): 591-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5708032

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Bilateral peninsula-shaped linear craniectomy for mild degrees of craniosynostosis: indication, technique and long-term results. Author(s): Erdincler P, Kaya AH, Kafadar A, Canbaz B, Kuday C. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 2004 April; 32(2): 64-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980584

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Binary nature and radiographic identifiability of craniosynostosis. Author(s): Pilgram TK, Vannier MW, Marsh JL, Kraemer BB, Rayne SC, Gado MH, Moran CJ, McAlister WH, Shackelford GD, Hardesty RA. Source: Investigative Radiology. 1994 October; 29(10): 890-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7852040

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Blood loss after endoscopic strip craniectomy for craniosynostosis. Author(s): Johnson JO, Jimenez DF, Barone CM. Source: Journal of Neurosurgical Anesthesiology. 2000 January; 12(1): 60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636624

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Blood loss and transfusion practice in the perioperative management of craniosynostosis repair. Author(s): Faberowski LW, Black S, Mickle JP. Source: Journal of Neurosurgical Anesthesiology. 1999 July; 11(3): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414670

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Blood loss during repair of craniosynostosis. Author(s): Meyer P, Renier D, Arnaud E, Jarreau MM, Charron B, Buy E, Buisson C, Barrier G. Source: British Journal of Anaesthesia. 1993 December; 71(6): 854-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8280553

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Blood salvage in craniosynostosis surgery. Author(s): Velardi F, Di Chirico A, Di Rocco C. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 November; 15(11-12): 695-710. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10603011

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Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. Author(s): Cole DE, Carpenter TO. Source: The Journal of Pediatrics. 1987 January; 110(1): 76-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3794889

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Brief clinical report: a sixth report (eighth case) of craniosynostosis-radial aplasia (Baller-Gerold) syndrome. Author(s): Pelias MZ, Superneau DW, Thurmon TF. Source: American Journal of Medical Genetics. 1981; 10(2): 133-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7315870

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Brief communication: the skull attributed to Mozart--craniosynostosis or not? Author(s): Hauser G, Kritscher H. Source: American Journal of Physical Anthropology. 1994 June; 94(2): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8085616

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Central nervous system phenotypes in craniosynostosis. Author(s): Aldridge K, Marsh JL, Govier D, Richtsmeier JT. Source: Journal of Anatomy. 2002 July; 201(1): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12171474

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Changes in orbital volume during childhood in cases of craniosynostosis. Author(s): Bentley RP, Sgouros S, Natarajan K, Dover MS, Hockley AD. Source: Journal of Neurosurgery. 2002 April; 96(4): 747-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990817

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Children with suspected craniosynostosis: a cost-effectiveness analysis of diagnostic strategies. Author(s): Medina LS, Richardson RR, Crone K. Source: Ajr. American Journal of Roentgenology. 2002 July; 179(1): 215-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076939

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Chronic headache as a sequela of rigid fixation for craniosynostosis. Author(s): Beck J, Parent A, Angel MF. Source: The Journal of Craniofacial Surgery. 2002 March; 13(2): 327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000898

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Clinical findings precede objective diagnostic testing in the identification of increased ICP in syndromic craniosynostosis. Author(s): David LR, Velotta E, Weaver RG Jr, Wilson JA, Argenta LC. Source: The Journal of Craniofacial Surgery. 2002 September; 13(5): 676-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12218797

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Comparison of perioperative blood salvage and postoperative reinfusion of drained blood during surgical correction of craniosynostosis in infants. Author(s): Orliaguet GA, Bruyere M, Meyer PG, Blanot S, Renier D, Carli PA. Source: Paediatric Anaesthesia. 2003 November; 13(9): 797-804. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617121

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Cranial remodeling to treat craniosynostosis by gradual distraction using a new device. Author(s): Imai K, Komune H, Toda C, Nomachi T, Enoki E, Sakamoto H, Kitano S, Hatoko M, Fujimoto T. Source: Journal of Neurosurgery. 2002 April; 96(4): 654-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990803

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Craniosynostosis and congenital heart anomalies associated with a maternal deletion of 15q15-22.1. Author(s): Shur N, Cowan J, Wheeler PG. Source: American Journal of Medical Genetics. 2003 August 1; 120A(4): 542-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884436

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Craniosynostosis and fetal exposure to sodium valproate. Author(s): Lajeunie E, Barcik U, Thorne JA, Ghouzzi VE, Bourgeois M, Renier D. Source: Journal of Neurosurgery. 2001 November; 95(5): 778-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702867

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Craniosynostosis and Klippel-Feil syndrome: a rare association. Author(s): Chattopadhyay A, Shah AM, Kher A, Bharucha BA, Karapurkar AP. Source: Indian J Pediatr. 1996 November-December; 63(6): 819-22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10830068

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Craniosynostosis and related limb anomalies. Author(s): Wilkie AO, Oldridge M, Tang Z, Maxson RE Jr. Source: Novartis Found Symp. 2001; 232: 122-33; Discussion 133-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277076

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Craniosynostosis associated with intracranial calcification: a novel recessive syndrome. Author(s): Longman C, Whiteford M, Koppel D, Donaldson M, Paterson W, Tolmie J. Source: Clinical Dysmorphology. 2003 October; 12(4): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564206

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Craniosynostosis associated with ocular and distal limb defects is very likely caused by mutations in a gene different from FGFR, TWIST, and MSX2. Author(s): Passos-Bueno MR, Armelin LM, Alonso LG, Neustein I, Sertie AL, Abe K, Pavanello Rde C, Elkis LC, Koiffmann CP. Source: American Journal of Medical Genetics. 2002 November 22; 113(2): 200-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407713

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Craniosynostosis due to premature closing of the sagittal suture. Author(s): Shaoul R, Toubi A. Source: Archives of Disease in Childhood. 2003 March; 88(3): 260. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598397

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Craniosynostosis in Alagille syndrome. Author(s): Kamath BM, Stolle C, Bason L, Colliton RP, Piccoli DA, Spinner NB, Krantz ID. Source: American Journal of Medical Genetics. 2002 October 1; 112(2): 176-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12244552

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Craniosynostosis in cherubism. Author(s): Stiller M, Urban M, Golder W, Tiziani V, Reichenberger E, Frege J, Opitz C, Peters H. Source: American Journal of Medical Genetics. 2000 December 11; 95(4): 325-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186885

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Craniosynostosis in transgenic mice overexpressing Nell-1. Author(s): Zhang X, Kuroda S, Carpenter D, Nishimura I, Soo C, Moats R, Iida K, Wisner E, Hu FY, Miao S, Beanes S, Dang C, Vastardis H, Longaker M, Tanizawa K, Kanayama N, Saito N, Ting K. Source: The Journal of Clinical Investigation. 2002 September; 110(6): 861-70. Erratum In: J Clin Invest 2002 November; 110(10): 1573. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235118

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Craniosynostosis with tracheal sleeve: a patient with Pfeiffer syndrome, tracheal sleeve and additional malformations in whom an FGFR2 mutation was found. Author(s): Zackai EH, McDonald-McGinn DM, Stolle C, Huff DS. Source: Clinical Dysmorphology. 2003 July; 12(3): 209. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564165

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Craniosynostosis, ectopia lentis, and congenital heart defects: further delineation of an autosomal dominant syndrome with incomplete penetrance. Author(s): Quercia NL, Teebi AS. Source: American Journal of Medical Genetics. 2002 January 1; 107(1): 38-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807865

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Craniosynostosis, telecanthus, scalp hair abnormalities, and sensorineural deafness in two sibs. Author(s): Megarbane A, Hersh JH, Chouery E, Fabre M. Source: American Journal of Medical Genetics. 2002 May 15; 109(4): 323-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992488

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Craniosynostosis. Author(s): Aviv RI, Rodger E, Hall CM. Source: Clinical Radiology. 2002 February; 57(2): 93-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11977940

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De novo del(7)(pter----p21.2::p15.2----qter) and craniosynostosis. Implications for critical segment assignment in the 7p2 monosomy syndrome. Author(s): Garcia-Esquivel L, Garcia-Cruz D, Rivera H, Plascencia ML, Cantu JM. Source: Annales De Genetique. 1986; 29(1): 36-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3487273

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De novo partial 2q3 trisomy/distal 7p22 monosomy in a malformed newborn with 7p deletion phenotype and craniosynostosis. Author(s): Fryns JP, Haspeslagh M, Agneessens A, van den Berghe H. Source: Annales De Genetique. 1985; 28(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3874588

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De novo terminal deletion 7p22.1--pter in a child without craniosynostosis. Author(s): Speleman F, Craen M, Leroy J. Source: Journal of Medical Genetics. 1989 August; 26(8): 528-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2671374

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Deciding on surgery: supporting parents of infants with craniosynostosis. Author(s): Letourneau N, Neufeld S, Drummond J, Barnfather A. Source: Axone. 2003 March; 24(3): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739353

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Delayed and progressive multiple suture craniosynostosis. Author(s): Reddy K, Hoffman H, Armstrong D. Source: Neurosurgery. 1990 March; 26(3): 442-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2320213

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Deletions of the short arm of chromosome 7 without craniosynostosis. Author(s): Carlo B, Lina A, Vincenzo Z. Source: Clinical Genetics. 1982 May; 21(5): 348-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7116680

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Detection of craniosynostosis by bone scanning. Author(s): Gates GF, Dore EK. Source: Radiology. 1975 June; 115(3): 665-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1129481

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Development of the frontal sinus and glabellar morphology after frontocranial remodeling for craniosynostosis in infancy. Author(s): Arnaud E, Renier D, Marchac D. Source: The Journal of Craniofacial Surgery. 1994 May; 5(2): 81-92; Discussion 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7918861

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Diagnostic practice and the estimated prevalence of craniosynostosis in Colorado. Author(s): Alderman BW, Fernbach SK, Greene C, Mangione EJ, Ferguson SW. Source: Archives of Pediatrics & Adolescent Medicine. 1997 February; 151(2): 159-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9041871

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Differential expression of fibroblast growth factor receptors in human digital development suggests common pathogenesis in complex acrosyndactyly and craniosynostosis. Author(s): Britto JA, Chan JC, Evans RD, Hayward RD, Jones BM. Source: Plastic and Reconstructive Surgery. 2001 May; 107(6): 1331-8; Discussion 133945. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11335797

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Difficult tracheal intubation induced by maxillary distraction devices in craniosynostosis syndromes. Author(s): Roche J, Frawley G, Heggie A. Source: Paediatric Anaesthesia. 2002 March; 12(3): 227-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903936

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Diffuse polymicrogyria associated with congenital hydrocephalus, craniosynostosis, severe mental retardation, and minor facial and genital anomalies. Author(s): Pavone L, Rizzo R, Pavone P, Curatolo P, Dobyns WB. Source: Journal of Child Neurology. 2000 July; 15(7): 493-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10921525

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Disseminated porokeratosis in an infant with craniosynostosis. Author(s): Judge MR, Michaels M, Sams VR, David TJ, Harper JI. Source: The British Journal of Dermatology. 1990 August; 123(2): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2400728

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Dissociated eye movements in craniosynostosis: a hypothesis revived. Author(s): Cheng H, Burdon MA, Shun-Shin GA, Czypionka S. Source: The British Journal of Ophthalmology. 1993 September; 77(9): 563-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8218052

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Distinctive syndrome of short stature, craniosynostosis, skeletal changes, and malformed ears. Author(s): Hurst JA, Winter RM, Baraitser M. Source: American Journal of Medical Genetics. 1988 January; 29(1): 107-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3344763

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Distraction osteogenesis and its application to the midface and bony orbit in craniosynostosis syndromes. Author(s): Toth BA, Kim JW, Chin M, Cedars M. Source: The Journal of Craniofacial Surgery. 1998 March; 9(2): 100-13; Discussion 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9586536

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Dual midfacial distraction osteogenesis: Le Fort III minus I and Le Fort I for syndromic craniosynostosis. Author(s): Satoh K, Mitsukawa N, Hosaka Y. Source: Plastic and Reconstructive Surgery. 2003 March; 111(3): 1019-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621171

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Early detection of craniosynostosis by 99mTc-pyrophosphate bone scanning. Author(s): de Rossi G, Focacci C. Source: Radiol Diagn (Berl). 1979; 20(3): 405-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=229510

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Early diagnosis and surgical indication in craniosynostosis. Author(s): Di Rocco C, Iannelli A, Velardi F. Source: Childs Brain. 1980; 6(4): 175-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7371441

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Early experience with poly L-lactic acid bioabsorbable fixation system for paediatric craniosynostosis surgery. Report of 3 cases. Author(s): Arai H, Sato K, Okuda O, Miyajima M, Hishii M, Nakanishi H, Ishii H. Source: Acta Neurochirurgica. 2000; 142(2): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10795893

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Early management of craniosynostosis using endoscopic-assisted strip craniectomies and cranial orthotic molding therapy. Author(s): Jimenez DF, Barone CM, Cartwright CC, Baker L. Source: Pediatrics. 2002 July; 110(1 Pt 1): 97-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093953

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Endoscopic craniectomy for early correction of craniosynostosis. Author(s): Barone CM, Jimenez DF. Source: Plastic and Reconstructive Surgery. 1999 December; 104(7): 1965-73; Discussion 1974-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11149758

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Endoscopic craniectomy for early surgical correction of sagittal craniosynostosis. Author(s): Jimenez DF, Barone CM. Source: Journal of Neurosurgery. 1998 January; 88(1): 77-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9420076

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Endoscopic strip craniectomy: a minimally invasive treatment for early correction of craniosynostosis. Author(s): Cartwright CC, Jimenez DF, Barone CM, Baker L. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 2003 June; 35(3): 130-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830660

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Endoscopic treatment of craniosynostosis. Author(s): Stelnicki EJ. Source: Atlas Oral Maxillofac Surg Clin North Am. 2002 March; 10(1): 57-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087866

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Enigma of raised intracranial pressure in patients with complex craniosynostosis: the role of abnormal intracranial venous drainage. Author(s): Taylor WJ, Hayward RD, Lasjaunias P, Britto JA, Thompson DN, Jones BM, Evans RD. Source: Journal of Neurosurgery. 2001 March; 94(3): 377-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11235939

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Enlarged parietal foramina and craniosynostosis in an American Indian child. Author(s): Mann RW. Source: Ajr. American Journal of Roentgenology. 1990 March; 154(3): 658. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2106245

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Epidemiology and genetics of craniosynostosis. Author(s): Wilkie AO. Source: American Journal of Medical Genetics. 2000 January 3; 90(1): 82-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10602123

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Erythropoietin therapy and acute preoperative normovolaemic haemodilution in infants undergoing craniosynostosis surgery. Author(s): Meneghini L, Zadra N, Aneloni V, Metrangolo S, Faggin R, Giusti F. Source: Paediatric Anaesthesia. 2003 June; 13(5): 392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791111

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Etiopathogenesis of craniosynostosis. Author(s): Cohen MM Jr. Source: Neurosurg Clin N Am. 1991 July; 2(3): 507-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1821298

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Evaluation of acute normovolemic hemodilution for surgical repair of craniosynostosis. Author(s): Hans P, Collin V, Bonhomme V, Damas F, Born JD, Lamy M. Source: Journal of Neurosurgical Anesthesiology. 2000 January; 12(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636618

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Evaluation of craniosynostosis with three-dimensional CT imaging. Author(s): Parisi M, Mehdizadeh HM, Hunter JC, Finch IJ. Source: Journal of Computer Assisted Tomography. 1989 November-December; 13(6): 1006-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2584477

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Evidence for locus heterogeneity in acrocephalosyndactyly: a refined localization for the Saethre-Chotzen syndrome locus on distal chromosome 7p--and exclusion of Jackson-Weiss syndrome from craniosynostosis loci on 7p and 5q. Author(s): van Herwerden L, Rose CS, Reardon W, Brueton LA, Weissenbach J, Malcolm S, Winter RM. Source: American Journal of Human Genetics. 1994 April; 54(4): 669-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8128964

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Evolving concepts in the pre-operative management and surgical treatment of craniosynostosis. Author(s): Francel PC, Persing JA. Source: Indian J Pediatr. 1991 March-April; 58(2): 183-90. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1879898

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Expanding cranioplasty for craniosynostosis and allied disorders. Author(s): Mori K, Sakamoto T, Nakai K. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1992 October; 8(7): 399-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1458498

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Experience in Egypt with 25 cases of craniosynostosis and forehead advancement. Author(s): Assaad A, Gheita AA. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1987; 3(4): 219-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3690558

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Expression profiles of craniosynostosis-derived fibroblasts. Author(s): Carinci F, Bodo M, Tosi L, Francioso F, Evangelisti R, Pezzetti F, Scapoli L, Martinelli M, Baroni T, Stabellini G, Carinci P, Bellucci C, Lilli C, Volinia S. Source: Molecular Medicine (Cambridge, Mass.). 2002 October; 8(10): 638-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477974

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Familial craniosynostosis due to Pro250Arg mutation in the fibroblast growth factor receptor 3 gene. Author(s): Hughes J, Nevin NC, Morrison PJ. Source: Ulster Med J. 2001 May; 70(1): 47-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11428324

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Familial craniosynostosis with oral anomalies. Author(s): Kernohan DC, Nevin NC, Dodge JA. Source: Developmental Medicine and Child Neurology. 1970 June; 12(3): 315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5433149

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Familial craniosynostosis, anal anomalies, and porokeratosis: CAP syndrome. Author(s): Flanagan N, Boyadjiev SA, Harper J, Kyne L, Earley M, Watson R, Jabs EW, Geraghty MT. Source: Journal of Medical Genetics. 1998 September; 35(9): 763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9733036

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Familial inheritance of coronal craniosynostosis. Author(s): Kosnik EJ, Gilbert G, Sayers MP. Source: Developmental Medicine and Child Neurology. 1975 October; 17(5): 630-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1183742

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Fertility treatments and craniosynostosis: California, Georgia, and Iowa, 1993-1997. Author(s): Reefhuis J, Honein MA, Shaw GM, Romitti PA. Source: Pediatrics. 2003 May; 111(5 Part 2): 1163-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728131

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FGFR2 mutation in clinically nonclassifiable autosomal dominant craniosynostosis with pronounced phenotypic variation. Author(s): Steinberger D, Reinhartz T, Unsold R, Muller U. Source: American Journal of Medical Genetics. 1996 December 2; 66(1): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8957519

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Fibroblast growth factor receptor mutations and craniosynostosis: three receptors, five syndromes. Author(s): Wilkie AO. Source: Indian J Pediatr. 1996 May-June; 63(3): 351-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10830010

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Fibroblast growth factor receptor-2 mutations in craniosynostosis. Author(s): Malcolm S, Reardon W. Source: Annals of the New York Academy of Sciences. 1996 June 8; 785: 164-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8702123

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Floating C-shaped orbital osteotomy for orbital rim advancement in craniosynostosis: preliminary report. Author(s): Persing JA, Jane JA, Park TS, Edgerton MT, Delashaw JB. Source: Journal of Neurosurgery. 1990 January; 72(1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2294180

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Fontaine-Farriaux craniosynostosis: second report in the literature. Author(s): Priolo M, De Toni T, Baffico M, Cama A, Seri M, Cusano R, Costabello L, Fondelli P, Capra V, Silengo M, Ravazzolo R, Lerone M. Source: American Journal of Medical Genetics. 2001 May 1; 100(3): 214-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343306

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Frequency of craniosynostosis in Yorkshire, UK. Author(s): Kirby PJ, Beverley DW, Batchelor AG. Source: Lancet. 1993 May 29; 341(8857): 1412-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8098816

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Frontonasal dysplasia with coronal craniosynostosis in three sibs. Author(s): Slover R, Sujansky E. Source: Birth Defects Orig Artic Ser. 1979; 15(5B): 75-83. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=526592

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Frontonasal dysplasia, coronal craniosynostosis, pre- and postaxial polydactyly and split nails: a new autosomal dominant mutant with reduced penetrance and variable expression? Author(s): Kwee ML, Lindhout D. Source: Clinical Genetics. 1983 September; 24(3): 200-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6627724

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Fronto-orbital re-operation in craniosynostosis. Author(s): Wall SA, Goldin JH, Hockley AD, Wake MJ, Poole MD, Briggs M. Source: British Journal of Plastic Surgery. 1994 April; 47(3): 180-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8193856

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Functional prognosis of surgical treatment of craniosynostosis. Author(s): Abe H, Ikota T, Akino M, Kitami K, Tsuru M. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1985; 1(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3986842

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Further evidence for an association between maternal smoking and craniosynostosis. Author(s): Honein MA, Rasmussen SA. Source: Teratology. 2000 September; 62(3): 145-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10935977

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Genetic and environmental risk factors for sagittal craniosynostosis. Author(s): Zeiger JS, Beaty TH, Hetmanski JB, Wang H, Scott AF, Kasch L, Raymond G, Jabs EW, VanderKolk C. Source: The Journal of Craniofacial Surgery. 2002 September; 13(5): 602-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12218784

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Genetic heterogeneity among craniosynostosis syndromes: mapping the SaethreChotzen syndrome locus between D7S513 and D7S516 and exclusion of JacksonWeiss and Crouzon syndrome loci from 7p. Author(s): Lewanda AF, Cohen MM Jr, Jackson CE, Taylor EW, Li X, Beloff M, Day D, Clarren SK, Ortiz R, Garcia C, et al. Source: Genomics. 1994 January 1; 19(1): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8188211

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Genetic perspectives on craniosynostosis and syndromes with craniosynostosis. Author(s): Cohen MM Jr. Source: Journal of Neurosurgery. 1977 December; 47(6): 886-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=925743

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Genetic study of nonsyndromic coronal craniosynostosis. Author(s): Lajeunie E, Le Merrer M, Bonaiti-Pellie C, Marchac D, Renier D. Source: American Journal of Medical Genetics. 1995 February 13; 55(4): 500-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7762595

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Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Author(s): Kan SH, Elanko N, Johnson D, Cornejo-Roldan L, Cook J, Reich EW, Tomkins S, Verloes A, Twigg SR, Rannan-Eliya S, McDonald-McGinn DM, Zackai EH, Wall SA, Muenke M, Wilkie AO. Source: American Journal of Human Genetics. 2002 February; 70(2): 472-86. Epub 2002 January 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781872

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Genomic structure, sequence, and mapping of human FGF8 with no evidence for its role in craniosynostosis/limb defect syndromes. Author(s): Yoshiura K, Leysens NJ, Chang J, Ward D, Murray JC, Muenke M. Source: American Journal of Medical Genetics. 1997 October 31; 72(3): 354-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9332670

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Gradual bone distraction in craniosynostosis. Preliminary results in seven cases. Author(s): do Amaral CM, Di Domizio G, Tiziani V, Galhardi F, Buzzo CL, Rinco T, Kharmandayan P, Bueno MA, Bolzani N, Sabbatini RM, Lopes LD, Lopes PF, Paiva B, Paiva RM, Turchiari LA. Source: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery / Nordisk Plastikkirurgisk Forening [and] Nordisk Klubb for Handkirurgi. 1997 March; 31(1): 25-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9075285

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Growth following craniofacial remodeling in craniosynostosis. Author(s): Salyer KE, Ubinas EE, Snively SL. Source: Prog Clin Biol Res. 1985; 187: 161-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4059231

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Growth of the cranial base in craniosynostosis. Author(s): Richtsmeier JT, Grausz HM, Morris GR, Marsh JL, Vannier MW. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1991 January; 28(1): 55-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2004097

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Heterozygous P250L mutation of fibroblast growth factor receptor 3 in a case of isolated craniosynostosis. Author(s): Schindler S, Friedrich M, Wagener H, Lorenz B, Preising MN. Source: Journal of Medical Genetics. 2002 October; 39(10): 764-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362036

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Histopathological and biochemical changes in the sutural region in craniosynostosis. Author(s): Pathak A, Sandhu BK, Radotra BD, Khandelwal N, Nath R, Kak VK. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2000 September; 16(9): 564-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11048630

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Holoprosencephaly and primary craniosynostosis: the Genoa syndrome. Author(s): Camera G, Lituania M, Cohen MM Jr. Source: American Journal of Medical Genetics. 1993 December 1; 47(8): 1161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8291548

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Hunterian Lecture. What can we learn about mechanisms of mutation from a study of craniosynostosis? Author(s): Moloney D. Source: Annals of the Royal College of Surgeons of England. 2001 January; 83(1): 1-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11212439

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Hunter-McAlpine craniosynostosis phenotype associated with skeletal anomalies and interstitial deletion of chromosome 17q. Author(s): Thomas JA, Manchester DK, Prescott KE, Milner R, McGavran L, Cohen MM Jr. Source: American Journal of Medical Genetics. 1996 April 24; 62(4): 372-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723067

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Hydrocephalus and craniosynostosis. Author(s): Cinalli G, Sainte-Rose C, Kollar EM, Zerah M, Brunelle F, Chumas P, Arnaud E, Marchac D, Pierre-Kahn A, Renier D. Source: Journal of Neurosurgery. 1998 February; 88(2): 209-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452225

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Hydrocephalus and mental retardation in craniosynostosis. Author(s): Noetzel MJ, Marsh JL, Palkes H, Gado M. Source: The Journal of Pediatrics. 1985 December; 107(6): 885-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4067746

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Hydrocephalus in craniosynostosis. Author(s): Collmann H, Sorensen N, Krauss J, Muhling J. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1988 October; 4(5): 279-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3242797

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Incidence of increased intracranial pressure after early surgical treatment of syndromic craniosynostosis. Author(s): Pollack IF, Losken HW, Biglan AW. Source: Pediatric Neurosurgery. 1996; 24(4): 202-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8873162

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Incidence of venous air embolism during craniectomy for craniosynostosis repair. Author(s): Faberowski LW, Black S, Mickle JP. Source: Anesthesiology. 2000 January; 92(1): 20-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10638894

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Increased bone formation and osteoblastic cell phenotype in premature cranial suture ossification (craniosynostosis). Author(s): De Pollack C, Renier D, Hott M, Marie PJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1996 March; 11(3): 401-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8852951

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Increased osteoblast apoptosis in apert craniosynostosis: role of protein kinase C and interleukin-1. Author(s): Lemonnier J, Hay E, Delannoy P, Fromigue O, Lomri A, Modrowski D, Marie PJ. Source: American Journal of Pathology. 2001 May; 158(5): 1833-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11337381

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Increased risk of craniosynostosis with higher antenatal maternal altitude. Author(s): Alderman BW, Zamudio S, Baron AE, Joshua SC, Fernbach SK, Greene C, Mangione EJ. Source: International Journal of Epidemiology. 1995 April; 24(2): 420-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7635605

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Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy. Author(s): Root S. Source: Teratology. 1995 May; 51(5): 289-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7482349

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Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy. Author(s): Alderman BW, Bradley CM, Greene C, Fernbach SK, Baron AE. Source: Teratology. 1994 July; 50(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7974250

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Infantile spasms in a patient with williams syndrome and craniosynostosis. Author(s): Morimoto M, An B, Ogami A, Shin N, Sugino Y, Sawai Y, Usuku T, Tanaka M, Hirai K, Nishimura A, Hasegawa K, Sugimoto T. Source: Epilepsia. 2003 November; 44(11): 1459-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636357

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Inhibition of apoptosis: a potential mechanism for syndromic craniosynostosis. Author(s): Dry GM, Yasinskaya YI, Williams JK, Ehrlich GD, Preston RA, Hu FZ, Gruss JS, Ellenbogen RG, Cunningham ML. Source: Plastic and Reconstructive Surgery. 2001 February; 107(2): 425-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11214058

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Insidious onset of familial craniosynostosis. Author(s): Cohen SR, Dauser RC, Gorski JL. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1993 July; 30(4): 401-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8399270

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Interstitial deletion of 2q associated with craniosynostosis, ocular coloboma, and limb abnormalities: cytogenetic and molecular investigation. Author(s): Nixon J, Oldridge M, Wilkie AO, Smith K. Source: American Journal of Medical Genetics. 1997 June 13; 70(3): 324-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9188674

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Intracranial hypertension after cranial vault decompression for craniosynostosis. Author(s): Campbell JW, Albright AL, Losken HW, Biglan AW. Source: Pediatric Neurosurgery. 1995; 22(5): 270-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547460

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Intracranial migration of fixation wires following correction of craniosynostosis in an infant. Author(s): Kosaka M, Miyanohara T, Wada Y, Kamiishi H. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 2003 February; 31(1): 15-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553921

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Intracranial pressure in single-suture craniosynostosis. Author(s): Cohen SR, Persing JA. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1998 May; 35(3): 194-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603551

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Intracranial pressure in single-suture craniosynostosis. Author(s): Thompson DN, Malcolm GP, Jones BM, Harkness WJ, Hayward RD. Source: Pediatric Neurosurgery. 1995; 22(5): 235-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547454

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Intracranial volume change in craniosynostosis. Author(s): Sgouros S, Hockley AD, Goldin JH, Wake MJ, Natarajan K. Source: Journal of Neurosurgery. 1999 October; 91(4): 617-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10507384

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Intraoperative autologous blood transfusion in the surgical correction of craniosynostosis. Author(s): Jimenez DF, Barone CM. Source: Neurosurgery. 1995 December; 37(6): 1075-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8584147

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Intra-operative scalp expansion for wound closure without tension in craniosynostosis operation--technical innovation. Author(s): Onishi K, Maruyama Y, Seiki Y. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 1995 October; 23(5): 317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8530708

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Investigation of the influences of biomechanical force on the ultrastructure of human sagittal craniosynostosis. Author(s): Ozaki W, Buchman SR, Muraszko KM, Coleman D. Source: Plastic and Reconstructive Surgery. 1998 October; 102(5): 1385-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773992

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Isolated craniosynostosis: prenatal ultrasound of scaphocephaly with polyhydramnios. Author(s): Huang HW, Lin H, Chang SY, Hsu YH, Hsu TY. Source: Chang Gung Med J. 2001 December; 24(12): 816-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858399

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Lack of ossification after cranioplasty for craniosynostosis: a review of relevant factors in 592 consecutive patients. Author(s): Prevot M, Renier D, Marchac D. Source: The Journal of Craniofacial Surgery. 1993 October; 4(4): 247-54; Discussion 255-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8110906

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Lacrimal gland prolapse in craniosynostosis syndromes and poor function congenital ptosis. Author(s): Jordan DR, Germer BA, Anderson RL, Morales L. Source: Ophthalmic Surg. 1990 February; 21(2): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2330205

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Lambdoid craniosynostosis. A 3D-computerized tomographic approach. Author(s): Leboucq N, Montoya P, Martinez Y, Castan P, Bourbotte G. Source: Journal of Neuroradiology. Journal De Neuroradiologie. 1993 March; 20(1): 2433. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8492173

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LeFort III internal distraction in syndromic craniosynostosis. Author(s): Holmes AD, Wright GW, Meara JG, Heggie AA, Probert TC. Source: The Journal of Craniofacial Surgery. 2002 March; 13(2): 262-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000884

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Letter: A newly recognized inherited syndrome of dwarfism, craniosynostosis, retinitis pigmentosa, and multiple congenital malformations. Author(s): Armendares S, Antillon F, Del Castillo V, Jimenez M. Source: The Journal of Pediatrics. 1974 December; 85(6): 872-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4370943

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Localization of craniosynostosis Adelaide type to 4p16. Author(s): Hollway GE, Phillips HA, Ades LC, Haan EA, Mulley JC. Source: Human Molecular Genetics. 1995 April; 4(4): 681-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7633418

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Longitudinal assessment of mental development in infants with nonsyndromic craniosynostosis with and without cranial release and reconstruction. Author(s): Kapp-Simon KA, Figueroa A, Jocher CA, Schafer M. Source: Plastic and Reconstructive Surgery. 1993 October; 92(5): 831-9; Discussion 840-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8415964

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Long-term neuropsychological effects of sagittal craniosynostosis on child development. Author(s): Magge SN, Westerveld M, Pruzinsky T, Persing JA. Source: The Journal of Craniofacial Surgery. 2002 January; 13(1): 99-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11887004

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Management of craniosynostosis. Author(s): Panchal J, Uttchin V. Source: Plastic and Reconstructive Surgery. 2003 May; 111(6): 2032-48; Quiz 2049. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12711969

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Management of nonsyndromic craniosynostosis. Author(s): Ghali GE, Sinn DP, Tantipasawasin S. Source: Atlas Oral Maxillofac Surg Clin North Am. 2002 March; 10(1): 1-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087862

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Management of pediatric head shape abnormalities: craniosynostosis and positional posterior plagiocephaly. Author(s): Weaver CE, Duncan JA. Source: Medicine and Health, Rhode Island. 2001 December; 84(12): 395-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11797582

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Management of syndromic craniosynostosis. Author(s): Tantipasawasin S, Sinn DP, Ghali GE. Source: Atlas Oral Maxillofac Surg Clin North Am. 2002 March; 10(1): 101-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087863

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Management of the ventricular shunt in posterior deformities of the skull in craniosynostosis. Author(s): Sun P, Shin JH, Persing JA. Source: The Journal of Craniofacial Surgery. 1997 January; 8(1): 38-41; Discussion 42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332297

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Marfanoid features and craniosynostosis: report of one case and review. Author(s): Lacombe D, Battin J. Source: Clinical Dysmorphology. 1993 July; 2(3): 220-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8287183

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Maternal smoking and craniosynostosis. Author(s): Kallen K. Source: Teratology. 1999 September; 60(3): 146-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10471899

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Maxillary volume growth in craniosynostosis. Author(s): Langford RJ, Sgouros S, Natarajan K, Nishikawa H, Dover MS, Hockley AD. Source: Plastic and Reconstructive Surgery. 2003 April 15; 111(5): 1598-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655203

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Meningioma and sagittal craniosynostosis in an infant: case report. Author(s): Chadduck WM, Boop FA, Blankenship JB, Husain M. Source: Neurosurgery. 1992 March; 30(3): 441-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1620313

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Mental development and learning disorders in children with single suture craniosynostosis. Author(s): Kapp-Simon KA. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1998 May; 35(3): 197-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603552

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Mental development in infants with nonsyndromic craniosynostosis with and without cranial release and reconstruction. Author(s): Kapp-Simon KA. Source: Plastic and Reconstructive Surgery. 1994 August; 94(2): 408-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8041840

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Molecular genetic advances in understanding craniosynostosis. Author(s): Robin NH. Source: Plastic and Reconstructive Surgery. 1999 March; 103(3): 1060-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10077104

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Monobloc and midface distraction osteogenesis in pediatric patients with severe syndromal craniosynostosis. Author(s): Meling TR, Tveten S, Due-Tonnessen BJ, Skjelbred P, Helseth E. Source: Pediatric Neurosurgery. 2000 August; 33(2): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070435

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Monozygotic twins with Crouzon syndrome: concordance for craniosynostosis and discordance for thumb duplication. Author(s): Lajeunie E, Bonaventure J, El Ghouzzi V, Catala M, Renier D. Source: American Journal of Medical Genetics. 2000 March 13; 91(2): 159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10748419

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More on craniosynostosis. Author(s): Williams MS. Source: Pediatric Annals. 1997 December; 26(12): 711. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9442528

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MR venography in children with complex craniosynostosis. Author(s): Rollins N, Booth T, Shapiro K. Source: Pediatric Neurosurgery. 2000 June; 32(6): 308-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971192

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Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans. Author(s): Liu YH, Tang Z, Kundu RK, Wu L, Luo W, Zhu D, Sangiorgi F, Snead ML, Maxson RE. Source: Developmental Biology. 1999 January 15; 205(2): 260-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9917362

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Multispiral three-dimensional computed tomography in the investigation of craniosynostosis: technique optimization. Author(s): Craven CM, Naik KS, Blanshard KS, Batchelor AG, Spencer JA. Source: The British Journal of Radiology. 1995 July; 68(811): 724-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7640927

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Mutation detection in FGFR2 craniosynostosis syndromes. Author(s): Hollway GE, Suthers GK, Haan EA, Thompson E, David DJ, Gecz J, Mulley JC. Source: Human Genetics. 1997 February; 99(2): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9048930

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Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome. Author(s): Sood S, Eldadah ZA, Krause WL, McIntosh I, Dietz HC. Source: Nature Genetics. 1996 February; 12(2): 209-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8563763

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Neonatal hyperthyroidism with accelerated skeletal maturation, craniosynostosis, and brachydactyly. Author(s): Riggs W Jr, Wilroy RS Jr, Etteldorf JN. Source: Radiology. 1972 December; 105(3): 621-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4642468

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Neonatal thyrotoxicosis: intellectual impairment and craniosynostosis in later years. Author(s): Daneman D, Howard NJ. Source: The Journal of Pediatrics. 1980 August; 97(2): 257-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7400892

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Neurocranial suture autotransplantation and periosteal dura stripping to provide a passive growth site in craniosynostosis--a case report. Author(s): Mommaerts MY, Staels PF. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 2003 August; 31(4): 202-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12914704

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Neurodevelopment in children with single-suture craniosynostosis and plagiocephaly without synostosis. Author(s): Panchal J, Amirsheybani H, Gurwitch R, Cook V, Francel P, Neas B, Levine N. Source: Plastic and Reconstructive Surgery. 2001 November; 108(6): 1492-8; Discussion 1499-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711916

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Neuropsychological evaluation in a series of 17 cases operated on for craniosynostosis. Author(s): Turtas S, Tondi M, Tola G, Sehrbundt Viale E, Martinez PL. Source: Acta Neurochirurgica. 1993; 120(3-4): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8460562

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New insights into craniosynostosis. Author(s): Flores-Sarnat L. Source: Semin Pediatr Neurol. 2002 December; 9(4): 274-91. Review. Erratum In: Semin Pediatr Neurol. 2003 June; 10(2): 159. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12523552

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New Marfanoid syndrome with craniosynostosis. Author(s): Furlong J, Kurczynski TW, Hennessy JR. Source: American Journal of Medical Genetics. 1987 March; 26(3): 599-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3565476

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New Zealand Maori family with the pro250arg fibroblast growth factor receptor 3 mutation associated with craniosynostosis. Author(s): Moko SB, Blandin de Chalain TM. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 2001 February; 29(1): 22-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467490

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Newer approaches to the treatment of craniosynostosis. Author(s): Chadduck WM, Cathey SL. Source: J Ark Med Soc. 1986 March; 82(10): 447-51. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2939057

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Newly recognised craniosynostosis syndrome that does not map to known disease loci. Author(s): Blair EM, Walsh S, Oldridge M, Wall SA, Wilkie AO. Source: American Journal of Medical Genetics. 2000 November 6; 95(1): 4-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074486

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Newly recognized autosomal dominant disorder with craniosynostosis. Author(s): Warman ML, Mulliken JB, Hayward PG, Muller U. Source: American Journal of Medical Genetics. 1993 June 1; 46(4): 444-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8357019

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Non-invasive aortic blood flow measurement in infants during repair of craniosynostosis. Author(s): Orliaguet GA, Meyer PG, Blanot S, Jarreau MM, Charron B, Cuttaree H, Perie AC, Carli PA, Renier D. Source: British Journal of Anaesthesia. 1998 November; 81(5): 696-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10193279

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Nonsyndromal craniosynostosis: longitudinal outcome following cranio-orbital reconstruction in infancy. Author(s): Polley JW, Charbel FT, Kim D, MaFee MF. Source: Plastic and Reconstructive Surgery. 1998 September; 102(3): 619-28; Discussion 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9727425

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Normal growth and development in a child with Baller-Gerold syndrome (craniosynostosis and radial aplasia). Author(s): Galea P, Tolmie JL. Source: Journal of Medical Genetics. 1990 December; 27(12): 784-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2074565

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Novel SNP at the common primer site of exon IIIa of FGFR2 gene causes error in molecular diagnosis of craniosynostosis syndrome. Author(s): Wong LJ, Chen TJ, Dai P, Bird L, Muenke M. Source: American Journal of Medical Genetics. 2001 August 15; 102(3): 282-5. Erratum In: Am J Med Genet 2002 April 22; 109(2): 166. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484208

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Observations on the temporal muscle in craniosynostosis. Author(s): Vargervik K, Miller AJ. Source: Birth Defects Orig Artic Ser. 1982; 18(1): 45-51. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7115913

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Obstructive sleep apnea attack in complex craniosynostosis. Author(s): Tajima S, Imai K. Source: Acta Otolaryngol Suppl. 1994; 517: 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7856442

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Occipital plagiocephaly: an epidemic of craniosynostosis? Author(s): Jones BM, Hayward R, Evans R, Britto J. Source: Bmj (Clinical Research Ed.). 1997 September 20; 315(7110): 693-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9314744

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Occipital remodeling and suboccipital decompression in severe craniosynostosis associated with tonsillar herniation. Author(s): Cinalli G, Chumas P, Arnaud E, Sainte-Rose C, Renier D. Source: Neurosurgery. 1998 January; 42(1): 66-71; Discussion 71-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9442505

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Occurrence of craniosynostosis in neonates exposed to cocaine and tobacco in utero. Author(s): Beeram MR, Abedin M, Shoroye A, Jayam-Trouth A, Young M, Reid Y. Source: Journal of the National Medical Association. 1993 November; 85(11): 865-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8107163

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Ocular anterior chamber dysgenesis in craniosynostosis syndromes with a fibroblast growth factor receptor 2 mutation. Author(s): Okajima K, Robinson LK, Hart MA, Abuelo DN, Cowan LS, Hasegawa T, Maumenee IH, Wang Jabs E. Source: American Journal of Medical Genetics. 1999 July 16; 85(2): 160-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10406670

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On the assets of CAD planning for craniosynostosis surgery. Author(s): Mommaerts MY, Jans G, Vander Sloten J, Staels PF, Van der Perre G, Gobin R. Source: The Journal of Craniofacial Surgery. 2001 November; 12(6): 547-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711821

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Operative positioning for patients undergoing repair of craniosynostosis. Author(s): Francel PC, Bell A, Jane JA. Source: Neurosurgery. 1994 August; 35(2): 304-6; Discussion 306. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7969839

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Ophthalmic features of craniosynostosis. Author(s): Newman SA. Source: Neurosurg Clin N Am. 1991 July; 2(3): 587-610. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1821306

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Outcome analysis for correction of single suture craniosynostosis using resorbable fixation. Author(s): Losken A, Williams JK, Burstein FD, Cohen SR, Hudgins R, Boydston W, Reisner A, Simms C. Source: The Journal of Craniofacial Surgery. 2001 September; 12(5): 451-5; Discussion 456-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11572250

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Pancraniosynostosis after surgery for single sutural craniosynostosis. Author(s): Greene CS Jr. Source: Pediatric Neurosurgery. 1998 September; 29(3): 127-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9838264

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Parental occupations as risk factors for craniosynostosis in offspring. Author(s): Bradley CM, Alderman BW, Williams MA, Checkoway H, Fernbach SK, Greene C, Bigelow PL, Reif JS. Source: Epidemiology (Cambridge, Mass.). 1995 May; 6(3): 306-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7619941

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Partial duplication of the long arm of chromosome 15: confirmation of a causative role in craniosynostosis and definition of a 15q25-qter trisomy syndrome. Author(s): Zollino M, Tiziano F, Di Stefano C, Neri G. Source: American Journal of Medical Genetics. 1999 December 22; 87(5): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10594876

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Pathogenesis of craniosynostosis. Author(s): Becker LE, Hinton DR. Source: Pediatric Neurosurgery. 1995; 22(2): 104-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7710971

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Pathogenesis of craniosynostosis. Author(s): Walker ML. Source: Pediatric Neurosurgery. 1995; 22(5): 280. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547462

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Patient with craniosynostosis and marfanoid phenotype (Shprintzen-Goldberg syndrome) and cloverleaf skull. Author(s): Saal HM, Bulas DI, Allen JF, Vezina LG, Walton D, Rosenbaum KN. Source: American Journal of Medical Genetics. 1995 July 17; 57(4): 573-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7573131

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Pediatric approach to craniosynostosis. Author(s): Liptak GS, Serletti JM. Source: Pediatrics in Review / American Academy of Pediatrics. 1998 October; 19(10): 352; Quiz 359. Review. Erratum In: Pediatr Rev 1999 January; 20(1): 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9785935

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Perioperative blood salvage during surgical correction of craniosynostosis in infants. Author(s): Dahmani S, Orliaguet GA, Meyer PG, Blanot S, Renier D, Carli PA. Source: British Journal of Anaesthesia. 2000 October; 85(4): 550-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11064613

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Perioperative specific management of blood volume loss in craniosynostosis surgery. Author(s): Kang JK, Lee SW, Baik MW, Son BC, Hong YK, Jung CK, Ryu KH. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1998 July; 14(7): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9726579

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Perioperative transcranial Doppler US to evaluate intracranial compliance in young children undergoing craniosynostosis repair surgery. Author(s): Westra SJ, Stotland MA, Lazareff J, Anderson CT, Sayre JW, Kawamoto H. Source: Radiology. 2001 March; 218(3): 816-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11230661

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Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family. Author(s): Golla A, Lichmer P, von Gernet S, Winterpacht A, Fairley J, Murken J, Schuffenhauer S. Source: Journal of Medical Genetics. 1997 August; 34(8): 683-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9279764

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Positron emission tomography studies confirm the need for early surgical intervention in patients with single-suture craniosynostosis. Author(s): David LR, Genecov DG, Camastra AA, Wilson JA, Argenta LC. Source: The Journal of Craniofacial Surgery. 1999 January; 10(1): 38-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10388424

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Post-operative mental development in patients with hydrocephalus and craniosynostosis. Author(s): Bhardwaj M, Rohtagi M. Source: Indian Pediatrics. 1994 October; 31(10): 1301-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7875803

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Prenatal identification of a G338E mutation in FGFR2 in a fetus without sonographic appearance of craniosynostosis. Author(s): Chen CP, Chern SR, Lin SP, Wang W, Tsai FJ. Source: Prenatal Diagnosis. 2003 February; 23(2): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12575031

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Prenatal sonographic appearance of asymmetric craniosynostosis: a case report. Author(s): Meilstrup JW, Botti JJ, MacKay DR, Johnson DL. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1995 April; 14(4): 307-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7602691

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Prenatal ultrasound diagnosis of fetal craniosynostosis. Author(s): Delahaye S, Bernard JP, Renier D, Ville Y. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 April; 21(4): 347-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704742

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Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis. Author(s): Moloney DM, Wall SA, Ashworth GJ, Oldridge M, Glass IA, Francomano CA, Muenke M, Wilkie AO. Source: Lancet. 1997 April 12; 349(9058): 1059-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9107244

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Primary craniosynostosis: imaging features. Author(s): Benson ML, Oliverio PJ, Yue NC, Zinreich SJ. Source: Ajr. American Journal of Roentgenology. 1996 March; 166(3): 697-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8623653

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Progressive postnatal craniosynostosis and increased intracranial pressure. Author(s): Connolly JP, Gruss J, Seto ML, Whelan MF, Ellenbogen R, Weiss A, Buchman SR, Cunningham ML. Source: Plastic and Reconstructive Surgery. 2004 April 15; 113(5): 1313-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15060342

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Prominent basal emissary foramina in syndromic craniosynostosis: correlation with phenotypic and molecular diagnoses. Author(s): Robson CD, Mulliken JB, Robertson RL, Proctor MR, Steinberger D, Barnes PD, McFarren A, Muller U, Zurakowski D. Source: Ajnr. American Journal of Neuroradiology. 2000 October; 21(9): 1707-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11039354

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Radiologic evaluation of the child with craniosynostosis. Author(s): Fernbach SK, Feinstein KA. Source: Neurosurg Clin N Am. 1991 July; 2(3): 569-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1821305

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Radiological case of the month. Sagittal and lambdoidal craniosynostosis. Author(s): Thorkelsson T, Mimouni F, Ball WS Jr, Wood BP. Source: Am J Dis Child. 1992 November; 146(11): 1311-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1415068

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Radioulnar synostosis and craniosynostosis in one family. Author(s): Berant M, Berant N. Source: The Journal of Pediatrics. 1973 July; 83(1): 88-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4768942

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Raised intracranial pressure in minimal forms of craniosynostosis. Author(s): Martinez-Lage JF, Alamo L, Poza M. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 January; 15(1): 11-5; Discussion 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10066015

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Craniosynostosis

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Rapid detection of FGFR mutations in syndromic craniosynostosis by temporal temperature gradient gel electrophoresis. Author(s): Higashimoto T, Yano S, Ito M, Clark-Sheehan NC, Cowan L, Boles RG. Source: Clinical Chemistry. 1999 November; 45(11): 2005-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10545072

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Rapid development of Chiari I malformation in an infant with Seckel syndrome and craniosynostosis. Case report and review of the literature. Author(s): Hopkins TE, Haines SJ. Source: Journal of Neurosurgery. 2003 May; 98(5): 1113-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744374

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Re: Sequence analysis of fibroblast growth factor receptor 2 (FGFR2) in Japanese patients with craniosynostosis. Sakai et al. J Craniofac. Surg. 2001, 12: 580-585. Author(s): Warren SM, Longaker MT. Source: The Journal of Craniofacial Surgery. 2002 July; 13(4): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140430

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Reattachment of the temporalis muscle to methacrylate in secondary surgery for craniosynostosis. Author(s): Cavadas PC. Source: Plastic and Reconstructive Surgery. 1996 September; 98(3): 573-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8701006

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Recurrent and multiple suture closures after craniectomy for craniosynostosis. Author(s): Norwood CW, Alexander E Jr, Davis CH Jr, Kelly DL Jr. Source: Journal of Neurosurgery. 1974 December; 41(6): 715-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4424010

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Reduction of operating time and blood transfusion for craniosynostosis by simulated surgery using three-dimensional solid models. Author(s): Imai K, Tsujiguchi K, Toda C, Enoki E, Sung KC, Sakamoto H, Kitano S, Hatoko M, Tajima S. Source: Neurol Med Chir (Tokyo). 1999 June; 39(6): 423-6; Discussion 427. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10396116

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Relationship between intracranial pressure and intracranial volume in craniosynostosis. Author(s): Fok H, Jones BM, Gault DG, Andar U, Hayward R. Source: British Journal of Plastic Surgery. 1992 July; 45(5): 394-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1638296

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Resorbable coupling fixation in craniosynostosis surgery: experimental and clinical applications. Author(s): Eppley BL, Sadove AM. Source: The Journal of Craniofacial Surgery. 1995 November; 6(6): 477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9020737

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Results of extended craniectomy including supraorbital advancement in premature coronal and frontal craniosynostosis. Author(s): Kaiser G, Bittel M. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery. [et Al] = Zeitschrift Fur Kinderchirurgie. 1991 August; 1(4): 227-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1931842

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Retrospective study of nonsyndromic craniosynostosis treated over a 10-year period. Author(s): Breugem CC, van R Zeeman BJ. Source: The Journal of Craniofacial Surgery. 1999 March; 10(2): 140-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10388415

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Rickets and secondary craniosynostosis associated with long-term antacid use in an infant. Author(s): Shetty AK, Thomas T, Rao J, Vargas A. Source: Archives of Pediatrics & Adolescent Medicine. 1998 December; 152(12): 1243-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9856439

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Rigid fixation of the calvaria in craniosynostosis without using "rigid" fixation. Author(s): Fearon JA. Source: Plastic and Reconstructive Surgery. 2003 January; 111(1): 27-38; Discussion 39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12496562

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Role of N-cadherin and protein kinase C in osteoblast gene activation induced by the S252W fibroblast growth factor receptor 2 mutation in Apert craniosynostosis. Author(s): Lemonnier J, Hay E, Delannoy P, Lomri A, Modrowski D, Caverzasio J, Marie PJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 May; 16(5): 832-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11341328

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Role of the extracellular matrix and growth factors in skull morphogenesis and in the pathogenesis of craniosynostosis. Author(s): Carinci P, Becchetti E, Bodo M. Source: Int J Dev Biol. 2000; 44(6): 715-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061436

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Craniosynostosis

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Safety and efficacy of remifentanil in craniosynostosis repair in children less than 1 year old. Author(s): Chiaretti A, Pietrini D, Piastra M, Polidori G, Savioli A, Velardi F, Ciano F, Di Rocco C. Source: Pediatric Neurosurgery. 2000 August; 33(2): 83-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070434

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Safety and efficacy of remifentanil infusion in craniosynostosis repair in infants. Author(s): Chiaretti A, Pietrini D. Source: Pediatric Neurosurgery. 2002 January; 36(1): 55-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11818751

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Sagittal craniosynostosis outcome assessment for two methods and timings of intervention. Author(s): Panchal J, Marsh JL, Park TS, Kaufman B, Pilgram T, Huang SH. Source: Plastic and Reconstructive Surgery. 1999 May; 103(6): 1574-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323690

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Sagittal craniosynostosis: cognitive development, behaviour, and quality of life in unoperated children. Author(s): Boltshauser E, Ludwig S, Dietrich F, Landolt MA. Source: Neuropediatrics. 2003 December; 34(6): 293-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681754

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Salvaged Le Fort II halo distraction for an unfavorable outcome of midfacial distraction using an internal device in syndromic craniosynostosis. Author(s): Mitsukawa N, Satoh K, Hayashi T, Uemura T, Hosaka Y. Source: Plastic and Reconstructive Surgery. 2004 April 1; 113(4): 1219-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15083024

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Screening of patients with craniosynostosis: molecular strategy. Author(s): Chun K, Teebi AS, Azimi C, Steele L, Ray PN. Source: American Journal of Medical Genetics. 2003 August 1; 120A(4): 470-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884424

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Secondary craniofacial management following initial correction of nonsyndromic craniosynostosis. Author(s): Shin JH, Sun P, Persing JA. Source: Clin Plast Surg. 1997 July; 24(3): 415-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9246510

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Sequence analysis of fibroblast growth factor receptor 2 ( FGFR2 ) in Japanese patients with craniosynostosis. Author(s): Sakai N, Tokunaga K, Yamazaki Y, Shida H, Sakata Y, Susami T, Nakakita N, Takato T, Uchinuma E. Source: The Journal of Craniofacial Surgery. 2001 November; 12(6): 580-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711827

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Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation. Author(s): Lajeunie E, El Ghouzzi V, Le Merrer M, Munnich A, Bonaventure J, Renier D. Source: Journal of Medical Genetics. 1999 January; 36(1): 9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9950359

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Short-limb skeletal dysplasias and craniosynostosis: what do they have in common? Author(s): Cohen MM Jr. Source: Pediatric Radiology. 1997 May; 27(5): 442-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9133360

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Simulation of oculomotility in Craniosynostosis patients. Author(s): Clement R, Nischal K. Source: Strabismus. 2003 December; 11(4): 239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730461

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Skull base growth in craniosynostosis. Author(s): Sgouros S, Natarajan K, Hockley AD, Goldin JH, Wake M. Source: Pediatric Neurosurgery. 1999 December; 31(6): 281-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702727

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Spectrum of craniosynostosis phenotypes associated with novel mutations at the fibroblast growth factor receptor 2 locus. Author(s): Pulleyn LJ, Reardon W, Wilkes D, Rutland P, Jones BM, Hayward R, Hall CM, Brueton L, Chun N, Lammer E, Malcolm S, Winter RM. Source: European Journal of Human Genetics : Ejhg. 1996; 4(5): 283-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8946174

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State of the art in craniofacial surgery: nonsyndromic craniosynostosis. Author(s): Williams JK, Ellenbogen RG, Gruss JS. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1999 November; 36(6): 471-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574666

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Subdural intracranial pressure monitoring in craniosynostosis: its role in surgical management. Author(s): Thompson DN, Harkness W, Jones B, Gonsalez S, Andar U, Hayward R. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1995 May; 11(5): 269-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7648567

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Surgical advancement influences perioperative care: a comparison of two surgical techniques for sagittal craniosynostosis repair. Author(s): Ririe DG, David LR, Glazier SS, Smith TE, Argenta LC. Source: Anesthesia and Analgesia. 2003 September; 97(3): 699-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933388

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Surgical correction of craniosynostosis in malignant osteopetrosis. Author(s): Krimmel M, Niemann G, Will B, Reinert S. Source: The Journal of Craniofacial Surgery. 2004 March; 15(2): 218-20; Discussion 221. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15167232

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Surgical correction of sagittal craniosynostosis: complications of the pi procedure. Author(s): Kanev PM, Lo AK. Source: The Journal of Craniofacial Surgery. 1995 March; 6(2): 98-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8601027

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Sutural exostoses, rib hyperostoses, craniosynostosis, mental retardation with focal fat deposition: Proteus syndrome? Author(s): Christianson AL, Van Allen MI. Source: American Journal of Medical Genetics. 1996 December 11; 66(2): 150-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8958321

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Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene. Author(s): Lowry RB, Jabs EW, Graham GE, Gerritsen J, Fleming J. Source: American Journal of Medical Genetics. 2001 November 22; 104(2): 112-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11746040

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The differential diagnosis of abnormal head shapes: separating craniosynostosis from positional deformities and normal variants. Author(s): Huang MH, Mouradian WE, Cohen SR, Gruss JS. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1998 May; 35(3): 204-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603553

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The effect of neurocranial surgery on basicranial morphology in isolated sagittal craniosynostosis. Author(s): DeLeon VB, Zumpano MP, Richtsmeier JT. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2001 March; 38(2): 134-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11294541

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The effectiveness of papilledema as an indicator of raised intracranial pressure in children with craniosynostosis. Author(s): Tuite GF, Chong WK, Evanson J, Narita A, Taylor D, Harkness WF, Jones BM, Hayward RD. Source: Neurosurgery. 1996 February; 38(2): 272-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8869054

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The elbow in syndromic craniosynostosis. Author(s): Anderson PJ, Hall CM, Evans RD, Hayward RD, Jones BM. Source: The Journal of Craniofacial Surgery. 1998 May; 9(3): 201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9693548

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The jugular foramen in complex and syndromic craniosynostosis and its relationship to raised intracranial pressure. Author(s): Rich PM, Cox TC, Hayward RD. Source: Ajnr. American Journal of Neuroradiology. 2003 January; 24(1): 45-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533326

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The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Author(s): Vajo Z, Francomano CA, Wilkin DJ. Source: Endocrine Reviews. 2000 February; 21(1): 23-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10696568

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The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences. Author(s): Ma L, Golden S, Wu L, Maxson R. Source: Human Molecular Genetics. 1996 December; 5(12): 1915-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8968743

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The pathogenesis of craniosynostosis in the fetus. Author(s): Warren SM, Longaker MT. Source: Yonsei Medical Journal. 2001 December; 42(6): 646-59. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11754148

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The Ptolemaic concept versus the Copernican system: rethinking the etiology and results of treatment in craniosynostosis in 2002. Author(s): Matic D, Vander Kolk CA. Source: Plastic and Reconstructive Surgery. 2003 February; 111(2): 929-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560723

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The treatment of craniosynostosis: an ethical perspective. Author(s): Ward C. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 1998 May; 35(3): 212-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603554

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The use of intraoperative autotransfusion during cranial vault remodeling for craniosynostosis. Author(s): Deva AK, Hopper RA, Landecker A, Flores R, Weiner H, McCarthy JG. Source: Plastic and Reconstructive Surgery. 2002 January; 109(1): 58-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786792

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The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children. Author(s): Fearon JA, Weinthal J. Source: Plastic and Reconstructive Surgery. 2002 June; 109(7): 2190-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12045535

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The use of recombinant erythropoietin in the reduction of transfusion rates in craniosynostosis repair in infants and children. Author(s): Przybylo HJ, Przybylo JH. Source: Plastic and Reconstructive Surgery. 2003 June; 111(7): 2485-6; Author Reply 2486-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794515

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The value of transcranial Doppler ultrasonography in craniosynostosis. Author(s): Govender PV, Nadvi SS, Madaree A. Source: The Journal of Craniofacial Surgery. 1999 May; 10(3): 260-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10530237

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Three-dimensional CT for pre- and postsurgical imaging of patients with craniosynostosis: correlation of operative procedure and radiologic imaging. Author(s): Boyle CM, Rosenblum JD. Source: Ajr. American Journal of Roentgenology. 1997 October; 169(4): 1173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9308485

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Three-dimensional CT maximum intensity projections of the calvaria: a new approach for diagnosis of craniosynostosis and fractures. Author(s): Medina LS. Source: Ajnr. American Journal of Neuroradiology. 2000 November-December; 21(10): 1951-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110553

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Toward understanding the pathogenesis of craniosynostosis through clinical and molecular correlates. Author(s): Jabs EW. Source: Clinical Genetics. 1998 February; 53(2): 79-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9611066

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Tracing craniosynostosis to its developmental stage through bone center displacement. Author(s): Mathijssen IM, van Splunder J, Vermeij-Keers C, Pieterman H, de Jong TH, Mooney MP, Vaandrager JM. Source: Journal of Craniofacial Genetics and Developmental Biology. 1999 April-June; 19(2): 57-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416148

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Transforming growth factor beta s and fibroblast growth factors and their receptors: role in sutural biology and craniosynostosis. Author(s): Cohen MM Jr. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1997 March; 12(3): 322-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9076574

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TWIST gene mutation in a patient with radial aplasia and craniosynostosis: further evidence for heterogeneity of Baller-Gerold syndrome. Author(s): Gripp KW, Stolle CA, Celle L, McDonald-McGinn DM, Whitaker LA, Zackai EH. Source: American Journal of Medical Genetics. 1999 January 15; 82(2): 170-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9934984

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Ultrasound diagnosis of craniosynostosis. Author(s): Miller C, Losken HW, Towbin R, Bowen A, Mooney MP, Towbin A, Faix RS. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2002 January; 39(1): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11772173

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•

Unclassifiable craniosynostosis phenotypes, FGFR2 Trp290 mutations, acanthosis nigricans, and unpaired cysteine mutations. Author(s): Cohen MM Jr. Source: American Journal of Medical Genetics. 2002 November 15; 113(1): 1-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12400057

•

Unknown syndrome: congenital heart disease, ptosis, hypodontia, and craniosynostosis. Author(s): Mehta L, Lewis I, Patton MA. Source: Journal of Medical Genetics. 1989 October; 26(10): 664-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2585465

•

Unusual association of congenital malformations: craniosynostosis, heart defect, abnormal intestinal innervation and urogenital abnormalities. Author(s): Van Nesselrooij BP, Spliet W, Beemer FA. Source: Clinical Dysmorphology. 1998 January; 7(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9546831

•

Upper airway obstruction and raised intracranial pressure in children with craniosynostosis. Author(s): Gonsalez S, Hayward R, Jones B, Lane R. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1997 February; 10(2): 367-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9042634

•

Use of scanning electron microscopy in the evaluation of craniosynostosis. Author(s): Ozaki W, Buchman SR. Source: The Journal of Craniofacial Surgery. 1998 January; 9(1): 30-8; Discussion 39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9558564

•

Use of three-dimensional ultrasonography in differentiating craniosynostosis from severe fetal molding. Author(s): Krakow D, Santulli T, Platt LD. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2001 April; 20(4): 427-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11316322

•

Using three-dimensional ultrasound to detect craniosynostosis in a fetus with Pfeiffer syndrome. Author(s): Benacerraf BR, Spiro R, Mitchell AG. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 September; 16(4): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11169319

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•

Value of computed tomography in the evaluation of craniosynostosis. Author(s): Goldstein SJ, Kidd RC. Source: Comput Radiol. 1982 November-December; 6(6): 331-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7166030

•

Venous air embolism during endoscopic strip craniectomy for repair of craniosynostosis in infants. Author(s): Tobias JD, Johnson JO, Jimenez DF, Barone CM, McBride DS Jr. Source: Anesthesiology. 2001 August; 95(2): 340-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11506103

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Venous air embolism in craniosynostosis surgery: what do we want to detect? Author(s): Meyer PG, Renier D, Orliaguet G, Blanot S, Carli P. Source: Anesthesiology. 2000 October; 93(4): 1157-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020781

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Venous intracranial haemodynamics in children undergoing operative treatment for the repair of craniosynostosis. A prospective study using transcranial colour-coded duplex sonography. Author(s): Mursch K, Enk T, Christen HJ, Markakis E, Behnke-Mursch J. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 March; 15(2-3): 110-6; Discussion 117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10230667

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Virchow and the pathogenesis of craniosynostosis: a translation of his original work. Author(s): Persing JA, Jane JA, Shaffrey M. Source: Plastic and Reconstructive Surgery. 1989 April; 83(4): 738-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2648432

•

Visual failure caused by raised intracranial pressure in craniosynostosis. Author(s): Stavrou P, Sgouros S, Willshaw HE, Goldin JH, Hockley AD, Wake MJ. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1997 February; 13(2): 64-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9105738

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2.

ALTERNATIVE MEDICINE CRANIOSYNOSTOSIS

AND

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to craniosynostosis. 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 craniosynostosis 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 “craniosynostosis” (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 craniosynostosis: •

Cranial vault expansion using transcutaneously activated magnetic implants. Author(s): Rinehart G, Forget T, Zografakis J, Manepalli AN, Pittman T. Source: Pediatric Neurosurgery. 1998 June; 28(6): 293-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9782206

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Cranial vault moulding by the transcutaneous activation of implanted magnets. Author(s): Pittman T, Rinehart GC, Hagen R, Saldana E. Source: Pediatric Neurosurgery. 1997 August; 27(2): 78-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9520079

•

Craniosynostosis in the Talmud. Author(s): Shapiro R.

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Source: Radiology. 1989 July; 172(1): 230. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2662253 •

Craniosynostosis: novel insights into pathogenesis and treatment. Author(s): Wilkie AO, Wall SA. Source: Current Opinion in Neurology. 1996 April; 9(2): 146-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8782984

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Cytokine therapy for craniosynostosis. Author(s): Mooney MP, Moursi AM, Opperman LA, Siegel MI. Source: Expert Opinion on Biological Therapy. 2004 March; 4(3): 279-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006724

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Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated premature cranial suture closure. Author(s): Kim HJ, Lee MH, Park HS, Park MH, Lee SW, Kim SY, Choi JY, Shin HI, Kim HJ, Ryoo HM. Source: Developmental Dynamics : an Official Publication of the American Association of Anatomists. 2003 July; 227(3): 335-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815619

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Hearing and otopathology in Apert syndrome. Author(s): Gould HJ, Caldarelli DD. Source: Arch Otolaryngol. 1982 June; 108(6): 347-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7201310

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Increased expression of protein kinase Calpha, interleukin-1alpha, and RhoA guanosine 5'-triphosphatase in osteoblasts expressing the Ser252Trp fibroblast growth factor 2 receptor Apert mutation: identification by analysis of complementary DNA microarray. Author(s): Lomri A, Lemonnier J, Delannoy P, Marie PJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 April; 16(4): 705-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11315998

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Venous air embolism during a craniofacial procedure. Author(s): Phillips RJ, Mulliken JB. Source: Plastic and Reconstructive Surgery. 1988 July; 82(1): 155-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3289061

Alternative Medicine 73

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

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

•

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

•

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

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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

•

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

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 3. DISSERTATIONS ON CRANIOSYNOSTOSIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to craniosynostosis. 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 “craniosynostosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on craniosynostosis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Craniosynostosis 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 craniosynostosis. 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: •

EFFECTS OF CULTURAL CRANIAL DEFORMATION AND CRANIOSYNOSTOSIS ON CRANIAL VENOUS SINUS AND MIDDLE MENINGEAL VESSEL PATTERN EXPRESSION by DEAN, VALERIE LYNN, PHD from INDIANA UNIVERSITY, 1995, 448 pages http://wwwlib.umi.com/dissertations/fullcit/9539949

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 4. BOOKS ON CRANIOSYNOSTOSIS Overview This chapter provides bibliographic book references relating to craniosynostosis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on craniosynostosis 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 “craniosynostosis” (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 craniosynostosis: •

Craniosynostosis: Diagnosis and Current Surgical Treatment Source: Chattanooga, TN: Tennessee Craniofacial Center, Erlanger Medical Center, T.C. Thompson Children's Hospital. 199x. 16 p. Contact: Available from Tennessee Craniofacial Center. Erlanger Medical Center, T.C. Thompson Children's Hospital, 975 East Third Street, Chattanooga, TN 37403. (800) 8257002 or (615) 778-9192. PRICE: Single copy free. Summary: This monograph reviews the diagnosis and current surgical treatment of infants with craniosynostosis, the premature closing of one or more of the bony gaps between the different bones of the skull. The author describes the work of the Tennessee Craniofacial Center, the need for team evaluation of patients with craniosynostosis, general advancements in the surgical treatment of these patients, the different types of synostosis (sagittal, metopic, unilateral coronal, bicoronal, lambdoid), craniosynostosis

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associated with Crouzon's and Apert's syndromes, preparation for surgery, and postoperative care. The author stresses that these infants are best evaluated and treated by a craniofacial center that utilizes the multidisciplinary team approach and provides a coordinated, comprehensive treatment plan with careful monitoring of growth and development. The monograph is illustrated with numerous, full-color, 'before and after' photographs of children with craniosynostosis. A glossary of related terms is included.

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 “craniosynostosis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “craniosynostosis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “craniosynostosis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

The Clinical Management of Craniosynostosis (CLINICS IN DEVELOPMENTAL MEDICINE) by Richard Hayward, et al; ISBN: 1898683360; http://www.amazon.com/exec/obidos/ASIN/1898683360/icongroupinterna

Chapters on Craniosynostosis In order to find chapters that specifically relate to craniosynostosis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and craniosynostosis 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 “craniosynostosis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on craniosynostosis: •

Recognition and Management of Dentofacial and Craniofacial Abnormalities Source: in Kwon, P.H. and Laskin, D.M. Clinician's Manual of Oral and Maxillofacial Surgery. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 426-437. 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: $58.00 plus shipping and handling. ISBN: 0867153962. Summary: This chapter is from a spiral-bound handbook that offers quick reference information to the oral and maxillofacial surgeon. The outline and chart-based format is designed to offer quick access to information that may be needed in situations that do not allow time for a leisurely perusal of textbooks and journals. This chapter presents a brief overview of a variety of dentofacial and craniofacial conditions and their surgical treatment. For each condition, a description of the physical and radiographic features is

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provided. The chapter emphasizes the importance of involving multiple specialties in the treatment of these abnormalities, especially orthodontics and oral and maxillofacial surgery. Surgical correction of these conditions should be undertaken only after diagnosis and comprehensive treatment planning have occurred, and only after the presurgical phase of orthodontic preparation is completed. Specific topics covered include vertical maxillary (upper jaw) excess, posterior maxillary vertical excess, maxillary vertical deficiency, maxillary anterior-posterior deficiency, mandibular (lower jaw) deficiency, mandibular prognathism (forward projection), condylar hyperplasia (overgrowth), hemimandibular hypertrophy, facial clefting (cleft lip and cleft palate), craniofacial microsomia (small size of portions of the face), mandibulofacial dysostosis (Treacher Collins syndrome, Nager syndrome, Miller syndrome), orbital hypertelorism (increased distance between the eyes), and craniosynostosis (premature fusion of the cranial sutures). •

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

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CHAPTER 5. MULTIMEDIA ON CRANIOSYNOSTOSIS Overview In this chapter, we show you how to keep current on multimedia sources of information on craniosynostosis. 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 craniosynostosis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “craniosynostosis” 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 “craniosynostosis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on craniosynostosis: •

Understanding Craniofacial Syndromes Source: Southfield, MI: Institute for Craniofacial and Reconstructive Surgery, Providence Hospital. 199x. (videocassette). Contact: Available from Institute for Craniofacial and Reconstructive Surgery. Providence Hospital, 16001 West Nine Mile Road, 3rd Floor Fisher Center, Southfield, MI 48075. Voice (800) 423-5801 or (810) 424-5800; Fax (810) 424-5881. PRICE: Donation to cover cost of duplicating and shipping. Summary: In this program, Dr. Ian Jackson of the Institute for Craniofacial and Reconstructive Surgery (Providence Hospital, Southfield, Michigan) describes a variety of craniofacial syndromes that occur in children. Dr. Jackson discusses the following cleft lip and palate, bilateral cleft lip and palate, hemifacial microsomia, craniosynostosis, plagiocephaly, Crouzon's syndrome, Apert's syndrome, hypertelorism, facial cleft, and hemangioma. For each syndrome, Dr. Jackson provides a

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brief etiology and a description of the treatment possible, including the role of each member of the patient care team, and the recommended timing of surgeries. Full-color photographs showing children with each syndrome are provided, depicting the child before and after corrective surgeries. •

Face Facts: Understanding Facial Disfigurement. Featured Segment: Hemifacial Microsomia Source: New York, NY: Forward Face. 1991. (videocassette). Contact: Available from Forward Face. 317 East 34th Street, Suite 901A, New York, NY 10036. Voice (800) 393-FACE or (212) 684-5860; Fax (212) 684-5864. PRICE: $10.00 for members; $15.00 for nonmembers. Summary: This videotape program is designed to help parents of children with craniofacial anomalies learn about positive opportunities for their children to grow and develop. Narrated by Cliff Robertson, the program emphasizes the importance of developing a positive self-image in children with facial differences. The film depicts numerous children and their families, as they cope with doctor's offices and surgeries, go to school, and live at home. In addition, basic facts about craniofacial anomalies are presented, including information about cleft lip and palate; craniosynostosis, including Apert, Crouzon's, Pfeiffer's, and Treacher-Collins syndrome; orbital hypertelorism; and hemifacial microsomia. Children with each of these anomalies are shown shortly after birth and as they grow. One segment explores the situation of hemifacial microstomia in more detail, including the role of hearing evaluation and hearing loss. The program emphasizes the need for early medical intervention, the role of a health care team, and the importance of support for the family and child. The video concludes with the tollfree telephone number of Forward Face, a support organization.

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CHAPTER

6.

PERIODICALS AND CRANIOSYNOSTOSIS

NEWS

ON

Overview In this chapter, we suggest a number of news sources and present various periodicals that cover craniosynostosis.

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

Endoscopic procedure for craniosynostosis shows promise Source: Reuters Medical News Date: July 19, 2002

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Link Between Craniosynostosis Mutation And Familial Deafness Syndrome Identified Source: Reuters Medical News Date: March 23, 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 “craniosynostosis” (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 “craniosynostosis” (or synonyms). If you know the name of a company that is relevant to craniosynostosis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “craniosynostosis” (or synonyms).

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Newsletters on Craniosynostosis Find newsletters on craniosynostosis using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “craniosynostosis.” 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.” Type “craniosynostosis” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Overview of Craniosynostosis for Patients and Parents Source: Forward Face Newsletter. 42(1 Special Educational Release): 1-4. 1993. Contact: Available from Forward Face Newsletter. 1611 Stratfield Road, Fairfield, CT 06432. (203) 374-8199. Summary: This special reprint article from the Forward Face Newsletter provides an overview of craniosynostosis, the premature closing of one or more of the sutures in the skull of a newborn child. The reprint discusses single suture involvement, the most common form of craniosynostosis; multiple suture involvement; and syndromal craniosynostosis, including that associated with Apert syndrome, Crouzon syndrome, or Pfeiffer syndrome. The author discusses surgical correction of craniosynostosis and the importance of support group involvement for the family. Numerous black-andwhite photographs illustrate the various conditions discussed.

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

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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 Institute4: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

4

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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.5 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:6 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

5

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

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

•

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

The NLM Gateway7 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.8 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “craniosynostosis” (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 2940 29 19 0 98 3086

HSTAT9 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.10 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.11 Simply search by “craniosynostosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

7

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

8

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). 9 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 10 11

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 Biologists12 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.13 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.14 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 Craniosynostosis In the following section, we will discuss databases and references which relate to the Genome Project and craniosynostosis. 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).15 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. 12 Adapted 13

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. 14 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. 15 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 “craniosynostosis” (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 craniosynostosis: •

Hunter-mcalpine Craniosynostosis Syndrome Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601379

•

Shprintzen-goldberg Craniosynostosis Syndrome Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182212 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 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,

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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 “craniosynostosis” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database16 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 Database17 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific 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 “craniosynostosis” (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).

16

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 17 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 craniosynostosis 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 craniosynostosis. 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 craniosynostosis. 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 “craniosynostosis”:

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Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Facial Injuries and Disorders http://www.nlm.nih.gov/medlineplus/facialinjuriesanddisorders.html Head and Brain Malformations http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html Infant and Toddler Health http://www.nlm.nih.gov/medlineplus/infantandtoddlerhealth.html 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 craniosynostosis. 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 options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Apert, Crouzon, and Other Craniosynostosis Syndromes Source: Limekiln, PA: AboutFace U.S.A. 1991. 33 p. Contact: Available from AboutFace U.S.A. P.O. Box 93, Limekiln, PA 19535. (800) 225FACE; Fax (610) 689-4479; E-mail: [email protected]; http://www.interlog.com/~abtface. PRICE: $2.00 each. Summary: This booklet discusses the impact and treatment of Apert and Crouzon's syndromes, two of the craniosynostosis syndromes. Topics covered include the definition of craniosynostosis; the effects of Apert and Crouzon syndromes on intelligence, hands and feet, eyes, hearing, mouth, speech and language development, and breathing; the multidisciplinary craniofacial team; the treatment, including surgical treatment of the mid-face, orthodontic treatment, and dental hygiene; and psychosocial considerations, including the role of various healthcare providers. 13 figures.

•

Guide to Understanding Craniosynostosis Source: Dallas, TX: Children's Craniofacial Association. 1993. 6 p.

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Contact: Available from Children's Craniofacial Association. 10210 North Central Expressway, Suite 230-LB 37, Dallas, TX 75231. (800) 535-3643 or (214) 368-3590. Fax (214) 368-3599. PRICE: $0.75 per booklet; minimum order of 20 booklets. Summary: This parents' guide is designed to answer questions that are frequently asked by parents of children with craniosynostosis, a condition in which the child's skull bones are prematurely fused together. Written in a question-and-answer format, the guide covers a definition of craniosynostosis; the diagnosis of craniosynostosis; the kinds of craniosynostosis; the causes of craniosynostosis; the treatment options; the timing for surgical procedures; the surgical procedures used to treat this craniosynostosis; determining the best place to have the child treated; and the members of the surgical team, including the craniofacial surgeon and the pediatric neurosurgeon. Two black-and white drawings illustrate the skull bones of a child and the skull in a child with untreated craniosynostosis. 2 figures. 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 craniosynostosis. 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. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to craniosynostosis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with craniosynostosis. 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 craniosynostosis. 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 “craniosynostosis” (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 “craniosynostosis”. 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 “craniosynostosis” (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 “craniosynostosis” (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.18

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

18

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)19: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

19

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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 craniosynostosis: •

Basic Guidelines for Craniosynostosis Craniosynostosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001590.htm Premature closure of sutures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001590.htm

•

Diagnostics and Tests for Craniosynostosis CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Films Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm Skull X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003802.htm

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X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Craniosynostosis Occipital-frontal circumference Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002379.htm

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

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

•

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

•

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

•

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

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CRANIOSYNOSTOSIS 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] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adverse Effect: An unwanted side effect of treatment. [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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

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Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Embolism: Occurs when the lungs over expand to the point that air bubbles are forced through the air sacs of the lungs into the circulatory system. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] 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] 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 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] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU]

Dictionary 113

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] 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] Anomalies: Birth defects; abnormalities. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aortic Stenosis, Supravalvular: A narrowing of the aorta in the region above the aortic valve. [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] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [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

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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] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] 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] 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] Auditory: Pertaining to the sense of hearing. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [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] 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] 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]

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Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [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] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] 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] 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 transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [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]

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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 Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [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] 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] 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] 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] 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] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] 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

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example, age, gender, ethnic origin). [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] 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 Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] 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]

Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH]

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Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Child Development: The continuous sequential physiological and psychological maturing of the child from birth up to but not including adolescence. It includes healthy responses to situations, but does not include growth in stature or size (= growth). [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [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 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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA

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molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [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]

Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [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] 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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1,

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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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [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] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the

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constitution. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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] 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 classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones. [NIH] Craniotomy: An operation in which an opening is made in the skull. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [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]

Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in

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body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [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] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [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] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic

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effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [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]

Dysgenesis: Defective development. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [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] 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] Ectopia Lentis: Congenital displacement of the lens resulting from defective zonule formation. [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 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] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [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] 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] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] 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] Epidemiological: Relating to, or involving epidemiology. [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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi

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and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] 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] Exophthalmos: Abnormal protrusion of both eyes; may be caused by endocrine gland malfunction, malignancy, injury, or paralysis of the extrinsic muscles of the eye. [NIH] Exostoses: Benign hypertrophy that projects outward from the surface of bone, often containing a cartilaginous component. [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] Extraocular: External to or outside of the eye. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [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] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH]

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Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Financial Management: The obtaining and management of funds for institutional needs and responsibility for fiscal affairs. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] 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] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frontal Sinus: One of the paired, but seldom symmetrical, air spaces located between the inner and outer compact layers of the frontal bone. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body

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through the rectum (flatus) or the mouth (burp). [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 Dosage: The number of copies of a given gene present in a cell or nucleus. An increase in gene dosage can result in the formation of higher levels of gene product, provided that the gene is not subject to autogenous regulation. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic 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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [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] 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] 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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH]

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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] 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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [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] 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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird

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and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] 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] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] 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] Hypertelorism: Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. [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] 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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer

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factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [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] 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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which

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regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interorbital: Between the orbits. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] 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] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an

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osseous and a membranous portion. [NIH] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Learning Disorders: Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include dyslexia, dyscalculia, and dysgraphia. [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] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] 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] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] 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

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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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [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] 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] 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] Malignant Hyperthermia: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia. [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] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological

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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] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [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 lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Methacrylate: A vinyl monomer. [NIH] Metopic: The suture separating the two halves of the frontal bone in infancy and occasionally persisting in the adult. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] 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] Mitotic: Cell resulting from mitosis. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

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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] 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] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [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] 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] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [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] 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] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida,

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anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] 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] 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]

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

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] 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] Orthodontics: A dental specialty concerned with the prevention and correction of dental and oral anomalies (malocclusion). [NIH] Orthotic Devices: Apparatus used to support, align, prevent, or correct deformities or to improve the function of movable parts of the body. [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] 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] 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] 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] 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] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU]

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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] 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] Papilledema: Swelling around the optic disk. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatric Dentistry: The practice of dentistry concerned with the dental problems of children, proper maintenance, and treatment. The dental care may include the services provided by dental specialists. [NIH] 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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Perioperative Care: Interventions to provide care prior to, during, and immediately after surgery. [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

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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] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] 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] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Pneumonia: Inflammation of the lungs. [NIH]

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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] 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] Polyhydramnios: Excess of amniotic fluid greater than 2,000 ml. It is a common obstetrical complication whose major causes include maternal diabetes, chromosomal disorders, isoimmunological disease, congenital abnormalities, and multiple gestations. [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] Porokeratosis: A rare, chronic, progressive autosomal dominant disorder seen most often in males and usually appearing in early childhood. It is characterized by the formation of slightly atrophic patches surrounded by an elevated, keratotic border. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH]

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Prolapse: The protrusion of an organ or part of an organ into a natural or artificial orifice. [NIH]

Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Proptosis: Forward projection or displacement especially of the eyeball : exophthalmos. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [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] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Ptosis: 1. Prolapse of an organ or part. 2. Drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation

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therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [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 cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [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] Renal agenesis: The absence or severe malformation of one or both kidneys. [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] 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] 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] 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

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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] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Sagittal: The line of direction passing through the body from back to front, or any vertical plane parallel to the medial plane of the body and inclusive of that plane; often restricted to the medial plane, the plane of the sagittal suture. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] 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] 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] 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

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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] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] 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] Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH]

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Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [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 Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

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] Stenosis: Narrowing or stricture of a duct or canal. [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] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supraorbital: The branch of the frontal nerve that passes through the supraorbital notch or foramen and is sensory for the upper eyelid, the conjunctiva, the eyebrow, the forehead, and the scalp up to the occipital bone. [NIH] Symphysis: A secondary cartilaginous joint. [NIH]

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Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synostosis: The joining of contiguous and separate bones by osseous tissue. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [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] Temporal Muscle: A masticatory muscle whose action is closing the jaws; its posterior portion retracts the mandible. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [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] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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.

Dictionary 147

[NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] 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] Thyrotoxicosis: The clinical syndrome that reflects the response of the peripheral tissues to an excess of thyroid hormone. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [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]

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Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital Abnormalities: Congenital structural abnormalities of the urogenital system. [NIH]

Urogenital System: All the organs involved in reproduction and the formation and release of urine. It includes the kidneys, ureters, bladder, urethra, and the organs of reproduction ovaries, uterus, fallopian tubes, vagina, and clitoris in women and the testes, seminal vesicles, prostate, seminal ducts, and penis in men. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Veins: The vessels carrying blood toward 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] Vertebral: Of or pertaining to a vertebra. [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] 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] 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]

Dictionary 149

Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [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] 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]

Williams Syndrome: A contiguous gene syndrome associated with a heterozygous microdeletion in the chromosomal region 7q11.23, encompassing the elastin gene. Clinical manifestations include supravalvular aortic stenosis (aortic stenosis, supravalvular), mental retardation, elfin facies, impaired visuospatial constructive abilities, and transient hypercalcemia in infancy. The condition affects both sexes, with onset at birth or in early infancy. [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] 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]

151

INDEX 3 3-dimensional, 30, 111 A Abdomen, 111, 116, 132, 138 Acanthosis Nigricans, 8, 65, 68, 111 Acetylcholine, 20, 111, 118, 136 Adaptability, 111, 117 Adenovirus, 18, 111 Adjustment, 19, 111 Adolescence, 79, 111, 118 Adverse Effect, 111, 144 Affinity, 8, 111, 112, 144 Agar, 111, 121 Agenesis, 112 Agonist, 112, 122, 136 Air Embolism, 46, 69, 72, 112 Air Sacs, 112 Airway, 4, 13, 29, 68, 112, 144 Airway Obstruction, 4, 68, 112 Algorithms, 112, 115 Alkaline, 112, 116 Alkaloid, 112, 119, 136 Alleles, 112, 128, 132 Alternative medicine, 84, 112 Amino Acid Sequence, 112, 113, 125, 127 Amino Acids, 112, 127, 138, 140, 141, 143, 147 Amniotic Fluid, 112, 140 Amphetamines, 112, 119 Ampulla, 112, 124 Anal, 41, 112, 126, 132 Analogous, 112, 147 Anatomical, 112, 118, 130, 143 Anemia, 95, 113, 115, 137 Anesthesia, 64, 112, 113, 133 Animal model, 11, 113 Anomalies, 6, 14, 16, 20, 34, 37, 41, 45, 82, 113, 137 Anterior chamber, 55, 113, 131 Antibacterial, 113, 145 Antibiotic, 113, 145 Antibodies, 11, 23, 113, 128, 139 Antibody, 11, 21, 111, 113, 119, 128, 129, 130, 142, 145 Anticoagulant, 113, 141 Antigen, 111, 113, 119, 129, 130 Anus, 112, 113, 119, 131 Anxiety, 5, 113

Aortic Stenosis, Supravalvular, 113, 149 Aplasia, 31, 32, 54, 67, 113, 123 Apnea, 113 Aponeurosis, 113, 126 Apoptosis, 8, 10, 15, 18, 46, 47, 113 Approximate, 19, 114 Aqueous, 114, 121, 124, 132 Arterial, 114, 117, 129, 141, 146 Aseptic, 114, 137 Asymptomatic, 28, 114 Ataxia, 94, 95, 114, 129, 146 Atrophy, 94, 95, 114 Auditory, 12, 13, 114 Autologous, 48, 114 Autonomic Nervous System, 114, 139 Axillary, 114 B Bacteria, 113, 114, 125, 134, 139, 145, 147 Basal Ganglia, 114, 116, 126 Basal Ganglia Diseases, 114 Base, 44, 63, 114, 127, 131, 140, 146 Basement Membrane, 114, 125 Benign, 115, 116, 125, 126, 128 Bifida, 115 Bilateral, 31, 81, 115, 142 Bile, 115, 132 Bioavailability, 23, 115 Biochemical, 4, 9, 16, 22, 45, 112, 115 Biological therapy, 115, 128 Biosynthesis, 115, 137 Biotechnology, 26, 84, 91, 93, 94, 95, 96, 115 Bladder, 115, 120, 130, 136, 141, 148 Blood Coagulation, 115, 116, 146 Blood pressure, 115, 129, 144 Blood transfusion, 48, 60, 66, 115, 128 Blood vessel, 115, 116, 117, 118, 124, 131, 132, 134, 144, 146, 147 Blood Viscosity, 115, 128 Blood Volume, 57, 115 Body Fluids, 115, 144 Bone Development, 9, 24, 115 Bone Marrow, 116, 125, 127, 130, 133, 135 Bone Remodeling, 22, 116 Bone Resorption, 116 Bone scan, 36, 38, 116, 143 Bowel, 112, 116, 136, 145 Brain Neoplasms, 116, 129, 146

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C Calcification, 34, 116 Calcium, 21, 116, 119, 129, 134, 137, 144 Carbon Dioxide, 116, 126 Carcinogens, 116, 136 Cardiopulmonary, 116, 128 Cardiopulmonary Bypass, 116, 128 Case report, 26, 31, 51, 53, 58, 60, 116 Cataracts, 28, 117 Catheter, 117, 131 Catheterization, 117, 131 Caudal, 117, 140 Cell Cycle, 117, 128 Cell Death, 8, 113, 117, 135 Cell Differentiation, 117, 144 Cell Division, 94, 114, 117, 128, 134, 139 Cell proliferation, 10, 15, 117, 144 Cell Survival, 117, 128 Central Nervous System, 111, 112, 114, 116, 117, 119, 126, 128, 129, 137 Central Nervous System Infections, 117, 128, 129 Cerebellar, 114, 117, 142 Cerebral, 4, 13, 114, 116, 117, 118, 124, 125, 126, 129, 138 Cerebral Cortex, 114, 117, 126 Cerebral Infarction, 117, 129 Cerebrospinal, 117, 129, 144 Cerebrospinal fluid, 117, 129, 144 Cerebrum, 117, 118, 147 Child Development, 50, 118 Chimera, 12, 118 Chin, 38, 118, 134 Cholinergic, 118, 136 Chondrocytes, 24, 118, 126 Chondrogenesis, 9, 118 Chorioretinitis, 118, 142 Choroid, 118, 142 Chromatin, 113, 118, 133 Chromosomal, 6, 14, 79, 118, 139, 140, 149 Chromosome, 6, 27, 30, 36, 40, 45, 56, 118, 132, 135, 147 Chronic, 33, 94, 118, 122, 124, 130, 131, 140 Chronic renal, 118, 140 Ciliary, 20, 118 Circulatory system, 112, 118 Cleft Lip, 25, 79, 81, 82, 118 Cleft Palate, 25, 44, 47, 48, 51, 63, 64, 65, 66, 67, 79, 118 Clinical trial, 4, 91, 118, 121, 142 Cloning, 115, 118 Coca, 119

Cocaine, 55, 119 Cochlea, 119, 130 Coculture, 18, 119 Cofactor, 119, 141, 146 Cognition, 119, 132 Collagen, 11, 21, 114, 119, 126, 137, 141 Collapse, 119, 144 Colloidal, 119, 123 Coloboma, 47, 119, 133 Colon, 31, 94, 119 Complement, 119, 120 Complementary and alternative medicine, 71, 73, 120 Complementary medicine, 71, 120 Compliance, 57, 120 Computational Biology, 91, 93, 120 Computed tomography, 52, 69, 120, 143 Computerized axial tomography, 120, 143 Computerized tomography, 120 Conception, 120, 126 Congenita, 120, 123 Conjunctiva, 120, 145 Connective Tissue, 116, 119, 120, 126, 132, 134, 146 Constitutional, 120, 135, 142 Contraindications, ii, 121 Control group, 6, 21, 121 Cornea, 113, 121 Cortex, 121, 142 Cortical, 20, 121, 143, 146 Craniocerebral Trauma, 114, 121, 128, 129, 146 Craniofacial Abnormalities, 24, 78, 121 Craniotomy, 23, 121 Culture Media, 23, 111, 121 Curative, 121, 146 Cutaneous, 14, 121 Cysteine, 68, 121 Cystine, 121 Cytokine, 21, 72, 121 Cytoplasm, 113, 121, 127, 133, 135, 143 Cytotoxic, 121, 144 D De novo, 22, 36, 121 Decompression, 47, 55, 121 Decompression Sickness, 121 Deletion, 22, 24, 34, 36, 45, 47, 113, 122 Dendrites, 122, 136 Dental Care, 122, 138 Depolarization, 122, 144 Developmental Biology, 7, 27, 52, 67, 122 Diagnostic procedure, 84, 122

153

Diastolic, 122, 129 Digestion, 115, 116, 122, 132 Dilation, 122, 129 Dimerization, 17, 122 Diploid, 122, 135, 139, 147 Direct, iii, 5, 14, 122, 142, 146 Discrete, 116, 122, 146 Disease Progression, 122, 142 Dissociation, 111, 122 Distal, 34, 36, 40, 122, 141 Dopamine, 119, 122, 136, 139 Dorsal, 123, 140, 145 Dorsum, 123, 126 Drug Interactions, 123 Duodenum, 115, 123, 124 Dura mater, 18, 123 Dwarfism, 24, 49, 123, 146 Dysgenesis, 55, 123 Dyslexia, 123, 132 Dysostosis, 17, 79, 123 Dysplasia, 42, 43, 95, 123 Dystrophic, 10, 123 Dystrophy, 94, 123 E Ectoderm, 123 Ectodermal Dysplasia, 79, 123 Ectopia Lentis, 35, 123 Effector, 111, 119, 123 Efficacy, 62, 123 Elastin, 119, 123, 149 Electrolyte, 123, 144 Electrons, 114, 123, 131, 141 Electrophoresis, 60, 123 Embryo, 115, 117, 123, 124, 127, 134, 137 Empirical, 6, 124 Emulsion, 124, 126 Encephalocele, 124, 136 Endemic, 124, 145 Endoscope, 124 Endoscopic, 32, 38, 39, 69, 83, 124 Endothelial cell, 124, 126, 146 End-stage renal, 118, 124, 140 Environmental Exposure, 25, 124, 136 Environmental Health, 90, 92, 124 Enzymatic, 116, 120, 124 Enzyme, 123, 124, 127, 135, 144, 146, 149 Epidemic, 55, 124, 145 Epidemiological, 14, 15, 20, 124 Epidermis, 123, 124 Epinephrine, 122, 124, 136, 148 Epithelial, 7, 125 Epithelial Cells, 125

Epithelium, 7, 114, 125, 131 Erythrocyte Volume, 115, 125 Erythrocytes, 113, 116, 125 Erythropoietin, 40, 66, 125 Essential Tremor, 94, 125 Eukaryotic Cells, 125, 130 Exon, 55, 125 Exophthalmos, 125, 141 Exostoses, 64, 125 Extracellular, 8, 11, 21, 61, 120, 125, 126, 137, 144 Extracellular Matrix, 11, 21, 61, 120, 125, 126, 137 Extracellular Space, 125 Extraocular, 29, 30, 125 Eye Infections, 111, 125 Eye Movements, 37, 125 F Facial, 5, 6, 24, 25, 31, 32, 37, 47, 48, 53, 54, 79, 81, 82, 98, 121, 125, 133 Facial Expression, 5, 125 Family Planning, 79, 91, 125 Fat, 64, 116, 125, 144 Femur, 125, 147 Fetus, 26, 58, 65, 68, 115, 125, 126, 140 Fibroblasts, 41, 126 Fibrosis, 79, 95, 126, 143 Fibula, 29, 126, 147 Financial Management, 7, 126 Fissure, 118, 119, 126 Fixation, 33, 38, 47, 56, 61, 126 Fluorescence, 22, 126 Fold, 19, 126 Foramen, 65, 118, 126, 145 Fovea, 126 Frontal Sinus, 37, 126 G Ganglia, 111, 114, 126, 135, 139 Ganglion, 20, 126, 137 Gas, 116, 122, 126, 129, 136, 148 Gene Dosage, 52, 127 Gene Expression, 7, 17, 19, 23, 95, 127 Gene Therapy, 18, 111, 127 Genetic Code, 127, 136 Genital, 37, 127, 148 Genitourinary, 127, 148 Genotype, 14, 127, 139 Germ Layers, 115, 123, 127 Gestation, 119, 127, 138 Gland, 49, 125, 127, 132, 138, 139, 141, 143, 145, 147 Glucose, 94, 127, 128

154

Craniosynostosis

Glycoproteins, 127, 131 Glycosaminoglycans, 127, 135 Governing Board, 127, 140 Granulocytes, 127, 144, 149 Growth factors, 9, 15, 23, 24, 61, 67, 128 Growth Plate, 9, 128 H Haptens, 111, 128 Headache, 33, 128, 129 Headache Disorders, 128 Helix-loop-helix, 16, 25, 128 Hemodilution, 40, 128 Hemoglobin, 113, 125, 128 Hemoglobinopathies, 127, 128 Hemoglobinuria, 94, 128 Hemorrhage, 121, 128 Hereditary, 8, 123, 128, 142, 143 Heredity, 127, 128 Heterogeneity, 40, 43, 67, 111, 128 Heterozygotes, 4, 16, 128 Homeostasis, 116, 128 Homologous, 112, 127, 128, 146 Homozygotes, 4, 129 Hormonal, 114, 129 Hormone, 123, 124, 125, 129, 144, 147 Human Development, 11, 90, 129 Hydrocephalus, 32, 37, 45, 46, 58, 129, 131 Hydrogen, 114, 129, 135 Hydrophobic, 8, 129 Hydroxylysine, 119, 129 Hydroxyproline, 119, 129 Hypercalcemia, 129, 149 Hyperostosis, 21, 129 Hyperplasia, 79, 129 Hypertelorism, 79, 81, 82, 129 Hypertension, 47, 129, 131 Hyperthyroidism, 53, 129 Hypertrophy, 79, 125, 129 Hypoplasia, 123, 129, 133 Hypothermia, 128, 129 I Immunization, 129, 140 Immunodeficiency, 94, 130 Immunology, 111, 130 Impairment, 5, 12, 17, 53, 114, 125, 130, 134 In situ, 18, 78, 130 In Situ Hybridization, 18, 130 In vitro, 15, 17, 19, 23, 115, 127, 130 In vivo, 11, 17, 18, 20, 23, 24, 127, 130 Incision, 130, 131 Incisor, 79, 130

Incontinence, 129, 130 Infancy, 19, 37, 54, 79, 130, 134, 149 Infection, 114, 115, 118, 125, 130, 132, 133, 149 Inflammation, 118, 125, 126, 130, 136, 139, 142 Infusion, 62, 130, 147 Initiation, 130, 147 Inner ear, 12, 130, 133 Innervation, 68, 130, 141 Insight, 9, 17, 130 Interleukin-1, 46, 72, 130 Interleukin-2, 130 Interorbital, 129, 131 Interstitial, 45, 47, 125, 131 Intestinal, 68, 131, 133 Intestines, 131 Intoxication, 131, 149 Intracellular, 7, 9, 130, 131, 144 Intracranial Hemorrhages, 129, 131, 146 Intracranial Hypertension, 128, 129, 131 Intraocular, 119, 131 Intravenous, 130, 131 Intrinsic, 8, 111, 114, 131 Intubation, 37, 117, 131 Invasive, 39, 54, 131, 133 Involuntary, 114, 125, 131, 142 Ion Channels, 20, 131, 146 Ionizing, 124, 131 Ions, 114, 122, 123, 129, 131 Iris, 113, 121, 131, 143 Ischemia, 114, 131 K Kb, 90, 131 Kidney Disease, 90, 95, 131 L Labyrinth, 119, 130, 131, 144, 148 Language Development, 98, 132 Learning Disorders, 51, 132 Lens, 117, 120, 123, 132 Lesion, 132, 144 Lethargy, 129, 132 Leukemia, 94, 127, 132 Ligament, 132, 141 Ligands, 9, 132 Linkage, 14, 25, 132 Linkage Disequilibrium, 25, 132 Lip, 81, 118, 132 Liver, 19, 115, 124, 125, 132, 143 Liver scan, 132, 143 Localization, 40, 49, 132 Localized, 19, 126, 130, 132, 139

155

Longitudinal study, 19, 132 Loop, 132 Lymph, 114, 118, 124, 132, 133 Lymph node, 114, 132, 133 Lymphatic, 130, 132, 133, 134 Lymphocytes, 113, 129, 130, 133, 149 Lymphoid, 113, 133 Lymphoma, 94, 133 M Macrophage, 130, 133 Magnetic Resonance Imaging, 133, 143 Malabsorption, 94, 133 Malformation, 13, 60, 133, 142 Malignancy, 111, 125, 133 Malignant, 64, 79, 94, 116, 133 Malignant Hyperthermia, 79, 133 Malnutrition, 114, 133, 135 Mammogram, 116, 133, 134 Mandible, 118, 133, 142, 146 Mandibulofacial Dysostosis, 79, 133 Masticatory, 133, 146 Maxillary, 37, 51, 79, 118, 133 Medial, 7, 30, 118, 133, 143, 145, 147 MEDLINE, 91, 93, 95, 133 Melanin, 131, 133, 134, 139, 148 Melanocytes, 133, 134 Melanoma, 94, 134 Melanosis, 111, 134 Membrane, 8, 118, 120, 122, 125, 131, 134, 139, 142, 144 Meninges, 117, 121, 123, 134 Mental Disorders, 134, 140, 141 Mental Health, iv, 4, 90, 92, 134, 140, 141 Mental Retardation, 13, 28, 37, 45, 64, 79, 96, 134, 149 Mesenchymal, 7, 9, 19, 24, 134 Mesoderm, 118, 134 Methacrylate, 60, 134 Metopic, 14, 17, 19, 77, 134 Microcalcifications, 116, 134 Microcirculation, 128, 134 Microorganism, 119, 134, 149 Microscopy, 68, 114, 134 Migration, 47, 118, 134 Mineralization, 8, 19, 22, 134 Mitosis, 114, 134 Mitotic, 8, 134 Modification, 134, 141 Molecule, 11, 23, 113, 114, 120, 122, 123, 128, 135, 139, 140, 142, 144, 148 Monocytes, 130, 135 Monosomy, 36, 135

Morphogenesis, 7, 11, 13, 24, 61, 135 Morphological, 14, 124, 133, 135 Morphology, 6, 14, 21, 37, 65, 135 Mucinous, 126, 135 Mucopolysaccharidoses, 79, 135 Muscle Fibers, 135 Muscular Atrophy, 94, 135 Mutate, 12, 135 Myasthenia, 29, 135 Myotonic Dystrophy, 94, 135 N Necrosis, 113, 117, 135 Neonatal, 29, 53, 135, 146 Neonatal period, 135, 146 Neoplasia, 94, 135 Nephropathy, 131, 135 Networks, 25, 135 Neural, 15, 19, 79, 124, 135 Neural tube defects, 15, 79, 135 Neurologic, 124, 129, 136 Neuromuscular, 111, 136 Neuromuscular Junction, 111, 136 Neuronal, 20, 136 Neurons, 20, 119, 122, 126, 136, 146 Neuroretinitis, 136, 142 Neurosurgeon, 5, 99, 136 Neurotransmitter, 111, 122, 131, 136, 144, 146 Nicotine, 20, 136 Night Blindness, 136, 143 Nitrogen, 112, 121, 126, 136, 147 Nuclear, 114, 123, 125, 126, 135, 136 Nuclei, 123, 127, 133, 134, 136, 137 Nucleic acid, 17, 127, 130, 136 Nucleus, 113, 114, 118, 121, 125, 127, 133, 135, 136, 146 O Ocular, 32, 34, 47, 55, 136 Oncogene, 94, 136 Opacity, 117, 136 Ophthalmology, 29, 30, 37, 126, 136 Optic Disk, 137, 138 Optic Nerve, 136, 137, 142 Orbit, 38, 137 Orbital, 29, 33, 42, 43, 54, 79, 82, 137 Organ Culture, 11, 24, 137 Orthodontics, 18, 79, 137 Orthotic Devices, 5, 137 Osseointegration, 115, 137 Ossification, 10, 46, 49, 137 Osteoblasts, 8, 10, 17, 18, 19, 22, 24, 72, 137 Osteocalcin, 22, 137

156

Craniosynostosis

Osteogenesis, 9, 10, 32, 38, 51, 115, 118, 137 Osteogenesis Imperfecta, 32, 137 Osteopetrosis, 64, 137 Osteoporosis, 116, 137 Osteotomy, 31, 42, 137 Overexpress, 22, 137 P Paediatric, 33, 37, 38, 40, 137 Palate, 25, 44, 47, 48, 51, 63, 64, 65, 66, 67, 79, 81, 82, 118, 138 Palliative, 138, 146 Pancreas, 138 Pancreatic, 94, 138 Pancreatic cancer, 94, 138 Papilledema, 65, 138 Paralysis, 125, 138, 141 Parietal, 39, 138 Parietal Lobe, 138 Paroxysmal, 94, 128, 138 Particle, 138, 147 Pathologic, 18, 114, 138, 142 Pathologic Processes, 114, 138 Pathophysiology, 11, 138 Patient Care Team, 82, 138 Patient Education, 98, 104, 106, 110, 138 Pediatric Dentistry, 10, 79, 138 Pelvic, 138, 141 Peptide, 126, 138, 140, 141 Perforation, 126, 138 Perinatal, 18, 21, 138 Perioperative, 32, 33, 57, 64, 138 Perioperative Care, 64, 138 Peripheral Nervous System, 20, 136, 138 Phallic, 126, 139 Pharmacologic, 113, 139, 147 Phenotype, 6, 10, 14, 25, 36, 45, 46, 57, 63, 139 Phenylalanine, 139, 148 Phosphates, 12, 139 Phospholipases, 139, 144 Phospholipids, 125, 139 Phosphorus, 116, 139 Physiologic, 18, 112, 115, 139, 142 Pigment, 133, 134, 139 Pilot study, 10, 139 Pituitary Gland, 126, 139 Plants, 112, 116, 119, 127, 135, 139 Plasma, 113, 115, 128, 139, 144 Plasma cells, 113, 139 Plasma Volume, 115, 139 Plasmid, 23, 139, 148

Platelet Activation, 139, 144 Pneumonia, 121, 139 Point Mutation, 8, 9, 28, 140 Polycystic, 95, 140 Polyhydramnios, 48, 140 Polypeptide, 112, 119, 140, 149 Porokeratosis, 37, 41, 140 Posterior, 15, 23, 50, 79, 112, 114, 118, 123, 131, 138, 140, 145, 146 Postnatal, 12, 22, 59, 140, 145 Postoperative, 21, 33, 78, 140 Postsynaptic, 140, 144, 146 Potentiates, 130, 140 Potentiation, 140, 144 Practice Guidelines, 92, 140 Precursor, 118, 122, 123, 124, 139, 140, 147, 148 Prenatal, 22, 48, 58, 124, 140 Preoperative, 30, 40, 140 Prevalence, 10, 37, 58, 140 Primary Prevention, 8, 140 Progression, 113, 140 Progressive, 36, 59, 117, 118, 135, 139, 140, 142, 148 Projection, 79, 137, 140, 141, 142 Prolapse, 49, 141 Proline, 119, 129, 141 Proptosis, 32, 141 Prospective study, 69, 132, 141 Prostate, 94, 141, 148 Protein C, 22, 112, 137, 141 Protein S, 95, 115, 127, 137, 141, 143 Proteins, 12, 26, 112, 113, 118, 119, 130, 135, 136, 138, 139, 141, 147 Proximal, 122, 141 Psychiatry, 126, 141 Psychic, 134, 141, 143 Psychoactive, 141, 149 Ptosis, 49, 68, 141 Public Health, 13, 14, 92, 141 Public Policy, 91, 141 Q Quality of Life, 62, 141 R Race, 134, 141 Radiation, 111, 124, 126, 131, 141, 142, 143, 149 Radiation therapy, 111, 141 Radioactive, 116, 129, 132, 136, 141, 142, 143 Radiology, 6, 32, 36, 52, 53, 57, 63, 72, 142 Randomized, 123, 142

157

Receptor, 8, 10, 11, 16, 28, 41, 42, 44, 45, 54, 55, 58, 60, 61, 63, 65, 72, 113, 122, 142, 144 Recombinant, 23, 66, 142, 148 Recombination, 127, 142 Rectum, 113, 119, 127, 130, 141, 142 Recurrence, 142 Red Nucleus, 114, 142 Refer, 1, 119, 126, 132, 142, 148 Reflex, 125, 142 Refraction, 142, 145 Regeneration, 126, 142 Regimen, 123, 142 Renal agenesis, 26, 142 Reoperation, 27, 142 Resorption, 116, 129, 142 Retina, 118, 132, 136, 137, 142, 143 Retinitis, 49, 142 Retinitis Pigmentosa, 49, 142 Retinoblastoma, 94, 143 Retroviral vector, 127, 143 Reversion, 17, 143 Ribosome, 143, 147 Rigidity, 133, 139, 143 Risk factor, 14, 15, 43, 56, 141, 143 S Sagittal, 3, 5, 14, 19, 23, 27, 35, 39, 43, 48, 50, 51, 59, 62, 64, 65, 77, 143 Salivary, 138, 143 Scans, 6, 19, 30, 143 Schizoid, 143, 149 Schizophrenia, 143, 149 Schizotypal Personality Disorder, 143, 149 Sclerae, 137, 143 Sclerosis, 94, 143 Screening, 5, 11, 12, 17, 25, 44, 62, 118, 143 Secretion, 123, 143 Seizures, 138, 143 Semen, 141, 143 Semicircular canal, 130, 144 Sequela, 33, 144 Sequencing, 25, 144 Sex Determination, 95, 144 Shunt, 50, 144 Side effect, 111, 115, 144, 147 Signal Transduction, 9, 24, 144 Skeletal, 4, 8, 9, 10, 14, 20, 22, 24, 38, 45, 53, 63, 65, 123, 144 Skeleton, 10, 22, 116, 125, 144, 147 Sleep apnea, 55, 144 Social Behavior, 6, 144 Social Environment, 141, 144

Sodium, 34, 144 Soft tissue, 116, 144 Somatic, 111, 134, 138, 145 Specialist, 100, 122, 145 Species, 124, 134, 141, 144, 145, 149 Specificity, 9, 12, 111, 145 Spectrum, 44, 63, 135, 145 Sperm, 118, 145 Sphenoid, 129, 145 Spina bifida, 16, 135, 145 Spinal cord, 117, 123, 126, 134, 135, 138, 142, 145 Spinal Nerves, 139, 145 Splenomegaly, 137, 145 Sporadic, 6, 143, 145 Staging, 143, 145 Stem Cells, 24, 125, 145 Stenosis, 145, 149 Stimulus, 130, 131, 142, 145, 146 Stool, 119, 130, 145 Subarachnoid, 128, 131, 145 Support group, 85, 145 Supraorbital, 61, 145 Symphysis, 118, 141, 145 Synapse, 20, 136, 146, 147 Synaptic, 136, 144, 146 Synaptic Transmission, 136, 146 Synergistic, 12, 146 Synostosis, 3, 5, 8, 14, 17, 19, 21, 53, 59, 77, 146 Systolic, 129, 146 T Talus, 146, 147 Telangiectasia, 95, 146 Temporal, 18, 55, 60, 128, 146 Temporal Muscle, 55, 146 Tendon, 126, 146 Thalamic, 114, 146 Thalamic Diseases, 114, 146 Thanatophoric Dysplasia, 8, 146 Therapeutics, 146 Threshold, 129, 146 Thrombin, 141, 146 Thrombomodulin, 141, 146 Thrombosis, 141, 147 Thyroid, 129, 147, 148 Thyroid Gland, 129, 147 Thyrotoxicosis, 53, 147 Tibia, 19, 126, 147 Tomography, 40, 58, 147 Toxic, iv, 20, 123, 124, 136, 147 Toxicity, 123, 147

158

Craniosynostosis

Toxicology, 92, 147 Transcription Factors, 7, 13, 25, 147 Transcutaneous, 71, 147 Transduction, 9, 144, 147 Transfection, 23, 115, 127, 147 Transfusion, 32, 66, 147 Translation, 69, 147 Transmitter, 111, 122, 131, 147 Trisomy, 36, 56, 147 Tryptophan, 119, 147 Tuberous Sclerosis, 79, 95, 147 Tumour, 126, 148 Tyrosine, 8, 122, 148 U Ultrasonography, 30, 66, 68, 148 Urethra, 141, 148 Urinary, 127, 129, 130, 148 Urine, 115, 128, 130, 148 Urogenital, 68, 127, 148 Urogenital Abnormalities, 68, 148 Urogenital System, 148 V VE, 34, 52, 148 Vector, 147, 148 Veins, 115, 148 Venous, 30, 39, 46, 69, 72, 117, 141, 148

Ventricle, 146, 148 Ventricular, 50, 129, 148 Vertebral, 115, 145, 148 Vestibular, 12, 148 Vestibule, 119, 130, 144, 148 Veterinary Medicine, 91, 148 Villi, 129, 148 Viral, 147, 148 Virus, 117, 143, 147, 148 Visual field, 143, 149 Vitro, 15, 19, 23, 149 Vivo, 20, 149 W White blood cell, 113, 133, 139, 149 Williams Syndrome, 47, 149 Withdrawal, 5, 149 Wound Healing, 126, 149 X Xenograft, 113, 149 X-ray, 109, 110, 120, 126, 133, 136, 141, 142, 143, 149 Y Yeasts, 139, 149 Z Zymogen, 141, 149

159

160

Craniosynostosis