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

MALIGNANT HYPERTHERMIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCE...

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MALIGNANT HYPERTHERMIA 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., 1960Malignant Hyperthermia: 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: 0-497-00700-2 1. Malignant Hyperthermia-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 malignant hyperthermia. 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 MALIGNANT HYPERTHERMIA .................................................................. 3 Overview........................................................................................................................................ 3 Federally Funded Research on Malignant Hyperthermia.............................................................. 3 E-Journals: PubMed Central ....................................................................................................... 10 The National Library of Medicine: PubMed ................................................................................ 11 CHAPTER 2. NUTRITION AND MALIGNANT HYPERTHERMIA ........................................................ 57 Overview...................................................................................................................................... 57 Finding Nutrition Studies on Malignant Hyperthermia............................................................. 57 Federal Resources on Nutrition ................................................................................................... 60 Additional Web Resources ........................................................................................................... 60 CHAPTER 3. ALTERNATIVE MEDICINE AND MALIGNANT HYPERTHERMIA .................................. 61 Overview...................................................................................................................................... 61 National Center for Complementary and Alternative Medicine.................................................. 61 Additional Web Resources ........................................................................................................... 63 General References ....................................................................................................................... 64 CHAPTER 4. PATENTS ON MALIGNANT HYPERTHERMIA .............................................................. 65 Overview...................................................................................................................................... 65 Patents on Malignant Hyperthermia........................................................................................... 65 Patent Applications on Malignant Hyperthermia ....................................................................... 71 Keeping Current .......................................................................................................................... 72 CHAPTER 5. BOOKS ON MALIGNANT HYPERTHERMIA .................................................................. 73 Overview...................................................................................................................................... 73 Book Summaries: Online Booksellers........................................................................................... 73 Chapters on Malignant Hyperthermia......................................................................................... 73 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 79 Overview...................................................................................................................................... 79 NIH Guidelines............................................................................................................................ 79 NIH Databases............................................................................................................................. 81 Other Commercial Databases....................................................................................................... 83 APPENDIX B. PATIENT RESOURCES ................................................................................................. 85 Overview...................................................................................................................................... 85 Patient Guideline Sources............................................................................................................ 85 Associations and Malignant Hyperthermia................................................................................. 87 Finding Associations.................................................................................................................... 88 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 91 Overview...................................................................................................................................... 91 Preparation................................................................................................................................... 91 Finding a Local Medical Library.................................................................................................. 91 Medical Libraries in the U.S. and Canada ................................................................................... 91 ONLINE GLOSSARIES.................................................................................................................. 97 Online Dictionary Directories ..................................................................................................... 98 MALIGNANT HYPERTHERMIA DICTIONARY .................................................................... 99 INDEX .............................................................................................................................................. 133

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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 malignant hyperthermia 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 malignant hyperthermia, 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 malignant hyperthermia, 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 malignant hyperthermia. 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 malignant hyperthermia, 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 malignant hyperthermia. 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 MALIGNANT HYPERTHERMIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on malignant hyperthermia.

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

Project Title: ANESTHETIC REACTIONS IN SURGERY Principal Investigator & Institution: Thomas, David Dale.; Professor; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 31-MAR-2004

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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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Malignant Hyperthermia

Summary: Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disorder in which exposure to volatile anesthetics or depolarizing muscle relaxants during surgery triggers uncontrolled Ca2+ release through sarcoplasmic reticulum (SR) ryanodine receptor (RYR) channels in skeletal muscle. The long term goal of this research is to define the molecular mechanisms that control RYR channels in situ, and to determine how anesthetics disrupt these mechanisms in the MH-susceptible (MHS) patient. Towards this goal, the proposed studies focus on identifying how agents that trigger or suppress the MH response affect the molecular interactions and structural events that underlie the gating of both MHS and normal RYR channels in situ. These studies will utilize the pig RYR1 Arg615Cys model of MH to address three specific aims. Aim I will determine the role of calmodulin (CaM) as a physiologic effector of MHS and normal RYR1 channels. [125I]CaM binding properties of the different channel isoforms (RYR1, RYR2, and RYR3) will be characterized, and compared with CaM's functional effects on the isolated channels as determined using [3H]ryanodine binding, Ca2+ flux, and single channel measurements. Effects of the Arg615Cys mutation on RYR1 [125I]CaM binding will also be characterized to determine the basis of the increased CaM-dependent activation of MHS channels. Related experiments will define CaM's in situ role controlling SR Ca2+ release in permeabilized fiber preparations, where the architecture of excitation-contraction (E-C) coupling remains intact. Aim II will define the mechanism of action of dantrolene, the specific treatment of MH. Experiments using recombinant, heterologously expressed RYRs will test the hypothesis that dantrolene inhibition of SR Ca release reflects a direct action of this agent at the RYR1. Characterization of dantrolene's functional effects on RYR1 in isolated preparations will be complemented with investigations of dantrolene's effects on SR CA2+ release in muscle fiber preparations. Aim III will identify the structural events that underlie gating of MHS and normal RYR1 channels. Fluorescently-labeled FKBP12 and CaM bound to specific regions on the RYR1 will reveal specific actions of the MHS mutation, dantrolene, and anesthetics on rotational and structural transitions of the RYR1 protein. MH remains a significant cuase of anesthetic-induced death and is an important model for a variety of disorders characterized by a loss of intracellular Ca2+ homeostasis. Identification of the molecular and biophysical mechanisms that underlie the triggering and suppression of the MH response will aid in the development of improved strategies for the prevention and treatment of this life-threatening response to anesthetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALMODULIN REGULATION OF SR CALCIUM RELEASE CHANNELS Principal Investigator & Institution: Fruen, Bradley R.; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This application is for an Independent Scientist Development Award (K02) for Dr. Bradley Fruen. The goal of this proposal is to promote the PI's independent research career by building on expertise in muscle membrane biochemistry/ion channel physiology, while fostering the development of novel biophysical approaches to understanding channel regulatory proteins that control muscle contraction. Muscle contraction is triggered by Ca2+ release from the sarcoplasmic reticulum (SR) via a macromolecular channel complex known as the ryanodine receptor (RYR). A long-term objective is to define the molecular mechanisms that control the RYR isoforms expressed in skeletal muscle (RYR1) and cardiac muscle (RYR2). Current aims focus on defining mechanisms by which calmodulin (CAM) acts

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as a regulatory subunit of the RYRs, modulating both channel activation and inhibition by Ca2+. Aim I will determine the mechanism underlying the isoform-specific regulation of RYR1 and RYR2 channels by CaM. Aim II will define the mechanism by which CaM Met residue oxidation alters productive interactions of CaM with RYR1 and RYR2 channels. Aim III will characterize allosteric interactions between CaM and FKBP sites on the RYRs, and their modulation by adrenergic stimulation. Aim IV will engineer fluorescent derivatives of CaM for resolving channel regulatory protein structural dynamics. Newly identified point mutants of CaM that selectively abolish either channel activation or inhibition will provide unique tools for defining the mechanism by which CaM functions as a molecular switch modulating the RYRs. Structural data based on mutagenesis and site-directed labeling will be supported by a battery of assays characterizing the functional activity of RYR channels isolated from pig cardiac and skeletal muscle. The RYR1 R615C pig provides a valuable model to examine mechanisms by which naturally occurring RYR mutations disrupt structure-function of the macromolecular channel complex in malignant hyperthermia and related channelopathies. Defining the role of RYR regulatory proteins is major challenge in understanding of the mechanisms that control Ca 2+ in muscle, and altered binding of these regulatory proteins is postulated to contribute to impaired contractile performance during oxidative stress, muscle fatigue, and heart disease. Proposed studies will further define structure-function relationships that underlie Ca regulation m muscle, and aid in the development of new strategies for treating neuromuscular and cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS Principal Investigator & Institution: Marks, Andrew R.; Professor of Molecular Cardiology; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 20-APR-1996; Project End 31-MAR-2006 Summary: (the applicant's description verbatim): The ryanodine receptor (RyR)/calcium (Ca) release channel (CRC) is required for excitation-contraction (EC) coupling in cardiac and skeletal muscle. The long term objective of this project is to elucidate structure-function relationships of the skeletal (RyR1) and cardiac (RyR2) CRCs. In the past 5 years important advances have been achieved in terms of identifying functional domains of the channels and in understanding the role of the FK506 binding protein (FKBP12/12.6) in regulating RyR function. Significant new findings and preliminary data include: 1) FKBP12/12.6 stabilize RyR1 and RyR2 function; 2) identification of the binding site for FKBP12/12.6 on RyR1 and RyR2; 2) RyRs are physically bound to neighboring RyRs and 2 or more channels can exhibit coupled gating in planar lipid bilayers (believed to be important for controlling EC coupling); 3) identification of the macromolecular signaling complex comprised of RyR, FKBP12/12.6, and protein kinase A (PKA), the phosphatases PP1 and PP2A and their corresponding anchoring/adaptor proteins; 4) PKA phosphorylation of RyR2 dissociates FKBP12.6 and regulates channel function; and 5) RyR2 function is defective in failing hearts due to PKA hyperphosphorylation of the channel which dissociates FKBP12.6 resulting in "leaky" channels. The aims of this proposal are designed to extend these observations in new directions to expand our understanding of the mechanisms that regulate RyR channel function and their role in human diseases. Aim 1 proposes to use site-directed mutagenesis and single channel recordings in planar lipid bilayers to identify key amino

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acid residues that form the FKBP12/12.6 binding sites in RyR1 and RyR2. Aim 2 is to use yeast two-hybrid screens and GST-pull downs to determine the components of the RyR1 and RyR2 macromolecular signaling complexes that regulate FKBP12/12.6 binding to the channels. Aim 3 proposes to identify regions of RyRl and RyR2 required for tetramer formation, and for binding between channels. Each of the molecules in the RyR macromolecular complex are potentially novel targets for probing mechanisms underlying EC coupling function and for treating human diseases. RyR2 regulation is defective in human heart failure and RyR1 is genetically linked to human diseases including malignant hyperthermia and central core disease. Pharmacologic manipulation, targeted at the regulation of FKBP12/12.6 binding to the channels and at phosphorylation/dephosphorylation of the channels, could ultimately provide novel approaches to treating these and other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRAMOLECULAR REGULATION OF RYANODINE RECEPTORS Principal Investigator & Institution: Shtifman, Alexander; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 19-AUG-2002 Summary: (provided by applicant): Ryanodine Receptor Ca(2+) release channels (RyRs) play a key role in regulation of intracellular [Ca(2+)] during the process of ExcitationContraction Coupling (EC Coupling). Full understanding of how the intracellular Ca(2+) is regulated is one of the fundamental goals of muscle research. It has been proposed that the domain-domain interactions within RyR are involved in stabilizing certain conformational states of the channel and could serve as the determining factors for the ability of certain RyR ligands to modulate Ca(2+) release. Identification and characterization of these molecular determinants of Ca(2+) release are the necessary steps for elucidating the mechanisms underlying intracellular Ca(2+) homeostasis. Work funded by this proposal will utilize molecular biological techniques to determine the regions of the RyR that interact with the central region of the channel, previously proposed to involved in domain-domain interactions. The role of these interactions in regulations of Ca(2+) release will be determined by monitoring macroscopic Ca(2+) transient using video rate light and confocal microscopy of RyR deficient myogenic cells expressing RyRs with mutations that are predicted to disrupt domain-domain interactions. This work will provide novel information needed to better understand the process of EC coupling and also may shed new light on the nature of muscle disorders such as malignant hyperthermia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR & ENVIRONMENTAL FACTORS INFLUENCING MH Principal Investigator & Institution: Allen, Paul D.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 10-MAR-2000; Project End 28-FEB-2004 Summary: Malignant hyperthermia (MH) is a pharmacogenetic disease of skeletal muscle. The long term objectives are to understand exactly how mutations of the ryanodine receptor (RyR1) and the L-type Ca2+ channel (alpha1DHPR) alter the process of excitation contraction coupling, and to define how pharmacologic agents and exposure to persistent ubiquitous environmental contaminants, such as polychlorinated biphenyls (PCBs), influence the phenotypic penetrance of human MH. HYPOTHESIS I: Mutations in RyR1 and the alpha1DHPR associated with human MH influence the

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ability of the alpha1DHPR and FKBP12 to interact with and regulate the function of RyR1. These changes lead to a common pattern of dysfunction of antegrade and retrograde signaling among these proteins upon exposure to MH triggering agents. The specific aims are 1) to create and express mutated cDNAs with RyR1 MH mutations Arg163Cys, Gly341Arg, Arg614Cys, Val2168Met, Arg2163Cys, and Arg2458His and the alpha1DHPR mutation, Arg1086His, in null skeletal myotubes and elucidate the effect of these mutations on macroscopic Ca2+ fluxes, [3H]ryanodine-binding, single-channel gating kinetics and the structural integrity of the FKBP12/RyR1 complex, and 2) to create four transgenic mouse lines (RyR1 Gly341Arg, Arg614Cys, Arg2458His and alpha1DHPR Arg1086His), each expressing one of these mutated proteins and measure their responses to halogenated volatile anesthetics and depolarizing neuromuscular blockers in vivo, and their responses to clinical in vitro contracture tests (IVCT). HYPOTHESIS II: The normal variation in concentrations of persistent ubiquitous environmental contaminants which are prevalent in human tissues can significantly influence the phenotypic penetrance of human MH mutations. The specific aims are 1) to define the mechanisms by which specific PCB congeners modify molecular events, and establish how these changes influence the MH phenotype by heightening the sensitivity and maximum response to pharmacologic agents, and 2) to administer relevant levels of environmental contaminants to transgenic mice carrying one of the MH mutations and determine changes in the ease with which animals show signs and symptoms of the syndrome, and/or changes the severity of their response to fixed doses of triggering agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR CHARACTERIZATION OF DANTROLENE BINDING SITE Principal Investigator & Institution: Parness, Jerome; Anesthesiology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2003; Project Start 01-FEB-1999; Project End 31-JUL-2008 Summary: (provided by applicant): Our long term goal is to understand the structural and functional bases of the interaction of dantrolene with the intracellular RyR/Ca release channel. We have identified a sequence domain called DP1 (a. a. 590-609) on the skeletal muscle ryanodine receptor (RyR1) as a target for dantrolene, a region tightly linked to mutations resulting in susceptibility to malignant hyperthermia. Dantrolene appears to interact with RyR1 rather than cardiac RyR2 despite an identical DP1 sequence. The weak interaction of dantrolene with RyR2, therefore, may reflect conformational constraints imparted by the rest of the channel or associated macromolecules. Key question regarding the molecular basis of dantrolene interaction with RyR isoforms are: What are the contextual requirements, both domain-domain and protein-protein interactions that determine dantrolene binding and pharmacologic activity in RyR isoforms? The specific hypothesis for this proposal is that residues 590609 on RyRldefine the major portion of the dantrolene binding site, and that conformation of this site determines the specific interaction of an RyR isoform with dantrolene and plays important role in the regulation of this Ca release channel. Two specific aims are designed to test this hypothesis: Aim 1, to define the structural and biochemical basis of dantrolene interaction with RyRI. Photoaffinity labeling with photoactive dantrolene congeners combined with mass spectrometry, and mutational analysis of identified sequences and functional analysis in Ca fluorescence measurements will be used. Aim 2, to explore the differential effects of dantrolene on

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RyR1 and RyR2 using pharmacological, immunological and molecular approaches. RyR1-RyR2 chimeras will be expressed in heterologous and homologous cells and their responses to dantrolene probed by Ca imaging and spectroscopy. The information gained will provide insight into the molecular mechanism by which dantrolene interferes with intracellular Ca release and lead to rational drug design for the therapy of Ca sensitive muscle diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CALCIUM RELEASE BY CALMODULIN IN MUSCLE Principal Investigator & Institution: Rodney, George G.; Biochem and Molecular Biology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 21-MAR-2003 Summary: (provided by applicant): Alterations in skeletal muscle sarcoplasmic reticulum (SR) calcium (Ca2+) release via the ryanodine receptor (RYR) Ca2+ release channel have been identified in a number of muscle diseases including malignant hyperthermia and central core disease. The regulation of SR Ca2+ release by endogenous ligands is also altered in these diseased muscles. This signifies the importance of understanding the regulation of RYR activity by endogenous modulators. Techniques utilizing laser scanning confocal microscopy and the Ca2+ indicator Fluo-3 have allowed the imaging of discrete localized Ca2+ release events (Ca2+ sparks) in functionally intact skeletal muscle. Examination of properties and frequency of occurrence of these events in response to either voltage or ligand stimulation is providing insight into the molecular control of SR Ca2+ release within the context of the functioning muscle fiber. The main objective of this proposal is to examine the modulation of the local control of SR Ca2+ release by calmodulin in functionally intact skeletal muscle fibers. Specifically, I intend to examine the effects of calmodulin on spontaneous and voltage activated skeletal muscle Ca2+ spark properties to gain insight into the role calmodulin plays in skeletal muscle excitation contraction coupling. The use of recombinant calmodulin, both wild type and a mutant that cannot bind Ca2+, will allow for the assessment of the role calmodulin plays in the activation, propagation and termination of these discrete localized Ca2+ release events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SIGNALING BETWEEN CALCIUM CHANNELS Principal Investigator & Institution: Beam, Kurt G.; Professor; Colorado State University-Fort Collins Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: The link between electrical excitation and contraction of a skeletal muscle cell (e-c coupling) involves signaling between two calcium channels: the dihydropyridine receptor (Oqs-DHPR) which is a voltage-gated Ca 2+ channel in the plasma membrane and ryanodine receptor type 1 (RyR1) which is a Ca 2+ release channel in the sarcoplasmic reticulum (SR). The long-term objective of this proposal is to understand the molecular basis for signaling between RyR1 and alpha1s- DHPR. The basic experimental approach will be to analyze the functional consequences of expressing cDNAs encoding DHPRs or RyRs in cultured muscle cells (myotubes) obtained from animals genetically null for one or more muscle proteins: dysgenic (alpha1s-DHPR null), dyspedic (RyR1 null), double knockout (null for both alpha1s DHPR and RyR1) and homerless (null for homer 1,2 and 3). The proposal has four specific aims. The first aim

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is to quantify "retrograde" signaling, whereby the RyR regulates entry of extracellular Ca 2+, for chimeric and mutant RyRs and to probe the functional importance of this entry. The second aim is to characterize the role of the accessory proteins homer and calmodulin in excitation-contraction coupling and in retrograde signaling. The third aim is to determine whether fluorescence energy resonance transfer (FRET) occurs between fluorescent protein-tagged alpha1-DHPRs assembled into plasma membranes at junctions with the SR and if it does to determine whether the FRET efficiency is affected by pharmacological manipulations of RyR1. The fourth aim is to explore interactions between DHPRs and RyRs in double knock-out (null for both alpha1s DHPR and RyR1), including a determination of whether skeletal-type e-c coupling can occur after expression in double knock-out myotubes of (alpha1c-DHPR and RyR2, the DHPR and RyR isoforms predominant in cardiac muscle. In addition to providing new insights into a basic muscle function, the proposed experiments will also provide knowledge essential for understanding the inherited human muscle diseases hypokalemic periodic paralysis (caused by mutations of alpha1s-DHPR) and malignant hyperthermia and central core disease (caused by mutations of RyR1). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL ANALYSIS OF THE CA++ RELEASE CHANNEL Principal Investigator & Institution: Hamilton, Susan L.; Professor and Head; Physiology/Molecul Biophysics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 30-SEP-2003 Summary: The opening of the pore in the transmembrane regions of the skeletal muscle Ca2+ release channel or ryanodine receptor (RYR1) is regulated by the binding of a variety of modulators to its cytoplasmic domains. Mutations that produce the two human diseases, central core disease (CCD) and malignant hyperthermia (MH), are also found frequently in cytoplasmic domains. The overall objective of this application is the elucidation of the molecular mechanisms by which binding of cytoplasmic modulators or the presence of mutations alter channel gating. The working hypothesis for this application is that the modulators bind close to and modulate infra or intersubunit contact sites that allosterically regulate the gating of the pore in the transmembrane domain. We also propose that the two cytoplasmic domains where the malignant hyperthermia and central core disease mutations occur interact to form an infra or intersubunit contact site close to the FKBP12 binding site and that mutations in either interacting partner alter both modulator binding and intersubunit communication. The specific aims are to: 1) delineate differences between the channel in the open and closed conformations to identify structural steps in channel gating, 2) assess the contributions of modulators to RYR1 structure, 3) localize the MH/CCD mutation sites and cysteine 3635 in the 3D structure of RYR1 and confirm protein-protein interactions. Structural information will be obtained using cryoelectron microscopy and computer reconstruction. Structural studies will be paralleled with functional analysis using single channel analysis of channels reconstituted into planar lipid bilayers and analysis of [3H]ryanodine binding. Interacting domains within RYR1 will be identified by assessing the ability of expressed fragments to interact using a biosensor assay and by identifying interacting regions using the yeast interaction trap. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE OF CHANNELS IN EXCITATION-CONTRACTION COUPLING Principal Investigator & Institution: Wagenknecht, Terence C.; Professor; Wadsworth Center Empire State Plaza Albany, Ny 12237 Timing: Fiscal Year 2002; Project Start 10-APR-1991; Project End 31-JUL-2005 Summary: (adapted from the applicant's description): Ryanodine receptors (RyRs) are intracellular calcium-releasing channels found in many cell types. They play a key role in regulating cytoplasmic [Ca2+], which controls such basic processes as contraction, secretion, mitosis, and neuroplasticity. RyRs are enriched in striated muscle where they play a central role in excitation-contraction (e-c) coupling, the process by which neuronal depolarization of the muscle membrane leads to release of Ca2+ from the lumen of the sarcoplasmic reticulum into the cytoplasm. A dozen or more mutations have been discovered in skeletal RyRs that together are responsible for two diseases, malignant hyperthermia and central core disease. The potentially important roles of RyRs in heart and brain function (and pathology) are also of current interest. RyRs are tetrameric complexes of net molecular masses greater than 2 million Da, making them the largest ion channels. Further, they interact with other proteins to form complex signaling assemblies, particularly in muscle. High-resolution electron microscopy of purified, frozen RyRs, combined with computerized three-dimensional image reconstruction techniques, offers the methodology for determining the structures of large, multicomponent complexes. This technology will be applied to the following problems: (1) How is the amino acid sequence of the RyR subunit distributed among the various structural domains (at least 11) that have been detected in 3D reconstructions. To accomplish this goal, structures will be determined of RyR:antibody (or Fab) complexes at moderate resolution (2-3nm) using antibodies that are specific to epitopes containing known amino acids within the overall RyR sequence (about 5,000 residues). In collaboration with another laboratory, an alternative molecular-biological approach will be pursued in which recombinant receptors will be prepared that contain epitope tags inserted into surface-exposed regions.(2) Where do natural protein ligands bind on the surface of the RyR? For example, the interaction between the RyR and the dihydropyridine receptor will be investigated, which is thought to be crucial to the mechanism in e-c coupling. (3) How do the three known genetic isoforms of the RyR differ in structure? Each isoform has slightly different properties and physiological roles. For example, only isoform 1 will mediate normal e-c coupling in skeletal muscle. Comparisons of the isoforms in defined functional states (e.g., open, closed, inactivated)in increasing detail will aid in understanding the molecular basis of their different properties and illuminate the structural basis of channel gating. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and 3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “malignant hyperthermia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for malignant hyperthermia in the PubMed Central database: •

Temperature perturbation studies of sarcoplasmic reticulum from malignant hyperthermia pig muscle. by Nelson TE, Bee DE.; 1979 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372197

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The porcine PHIcDNA linked to the halothane gene detects a HindIII and XbaI RFLP in normal and malignant hyperthermia susceptible pigs. by Brenig B, Jurs S, Brem G.; 1990 Jan 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330307

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The porcine PHIcDNA linked to the halothane gene detects a NotI RFLP in normal and malignant hyperthermia susceptible pigs. by Brenig B, Jurs S, Brem G.; 1990 Jan 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330308

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

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A breakthrough in the genetic diagnosis of malignant hyperthermia. Author(s): Robinson RL, Hopkins PM. Source: British Journal of Anaesthesia. 2001 February; 86(2): 166-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573654

The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A case of suspected malignant hyperthermia during desflurane administration. Author(s): Celebioglu B. Source: Anesthesia and Analgesia. 1998 April; 86(4): 916. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9539628

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A case of suspected malignant hyperthermia during desflurane administration. Author(s): Michalek-Sauberer A, Fricker R, Gradwohl I, Gilly H. Source: Anesthesia and Analgesia. 1997 August; 85(2): 461-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9249131

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A fatal case of malignant hyperthermia complicated by generalized compartment syndrome and rhabdomyolysis. Author(s): Green G. Source: Acta Anaesthesiologica Scandinavica. 2003 May; 47(5): 619-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12699524

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A genome wide search for susceptibility loci in three European malignant hyperthermia pedigrees. Author(s): Robinson RL, Monnier N, Wolz W, Jung M, Reis A, Nuernberg G, Curran JL, Monsieurs K, Stieglitz P, Heytens L, Fricker R, van Broeckhoven C, Deufel T, Hopkins PM, Lunardi J, Mueller CR. Source: Human Molecular Genetics. 1997 June; 6(6): 953-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9175745

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A new mutation in the skeletal ryanodine receptor gene (RYR1) is potentially causative of malignant hyperthermia, central core disease, and severe skeletal malformation. Author(s): Rueffert H, Olthoff D, Deutrich C, Schober R, Froster UG. Source: American Journal of Medical Genetics. 2004 January 30; 124A(3): 248-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708096

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A noninvasive investigation of muscle energetics supports similarities between exertional heat stroke and malignant hyperthermia. Author(s): Bendahan D, Kozak-Ribbens G, Confort-Gouny S, Ghattas B, FigarellaBranger D, Aubert M, Cozzone PJ. Source: Anesthesia and Analgesia. 2001 September; 93(3): 683-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11524341

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A suspected case of delayed onset malignant hyperthermia with desflurane anesthesia. Author(s): Papadimos TJ, Almasri M, Padgett JC, Rush JE. Source: Anesthesia and Analgesia. 2004 February; 98(2): 548-9, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742405

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A suspected malignant hyperthermia episode during desflurane anesthesia. Author(s): Lowes R, Mayhew JF. Source: Anesthesia and Analgesia. 1998 February; 86(2): 449-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9459273

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Abnormal uptake and release of Ca2+ ions from human malignant hyperthermiasusceptible sarcoplasmic reticulum. Author(s): O'Sullivan GH, McIntosh JM, Heffron JJ. Source: Biochemical Pharmacology. 2001 June 15; 61(12): 1479-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377377

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Absence of malignant hyperthermia in an infant with Wolf-Hirschhorn syndrome undergoing anesthesia for ophthalmic surgery. Author(s): Sammartino M, Crea MA, Sbarra GM, Fiorenti M, Mascaro A. Source: Journal of Pediatric Ophthalmology and Strabismus. 1999 January-February; 36(1): 42-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9972515

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An analysis of the predictive probability of the in vitro contracture test for determining susceptibility to malignant hyperthermia. Author(s): Hopkins PM, Ellis FR, Halsall PJ, Stewart AD. Source: Anesthesia and Analgesia. 1997 March; 84(3): 648-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9052318

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An episode of malignant hyperthermia followed by a persisting muscle weakness. Author(s): Michalek-Sauberer A, Gilly H. Source: Anesthesiology. 1998 April; 88(4): 1128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579529

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An image analysis study of vastus lateralis muscle fibers in malignant hyperthermia susceptible patients. Author(s): Zukowski F, De Craemer D, Van den Branden C, De Cauwer H, Heytens L, Martin JJ. Source: Clin Neuropathol. 1998 January-February; 17(1): 6-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9496533

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Anaesthetic management of a child with a positive family history of malignant hyperthermia for posterior fossa surgery in the sitting position. Author(s): Wootton MA, Lockie J. Source: Paediatric Anaesthesia. 2001 July; 11(4): 498-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442873

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Anaesthetic management of coronary artery bypass grafting in a patient with central core disease and susceptibility to malignant hyperthermia on statin therapy. Author(s): Johi RR, Mills R, Halsall PJ, Hopkins PM. Source: British Journal of Anaesthesia. 2003 November; 91(5): 744-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570802

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Analysis of anaesthesia in patients suspected to be susceptible to malignant hyperthermia before diagnostic in vitro contracture test. Author(s): Bendixen D, Skovgaard LT, Ording H. Source: Acta Anaesthesiologica Scandinavica. 1997 April; 41(4): 480-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9150775

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Astute assessment by a perioperative nurse in an expanded role saves patient from malignant hyperthermia. Author(s): Murphy JM. Source: Aorn Journal. 1997 July; 66(1): 146. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9220072

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Attenuation of serotonin-induced contractures in skeletal muscle from malignant hyperthermia-susceptible patients with dantrolene. Author(s): Wappler F, Scholz J, von Richthofen V, Fiege M, Kochling A, Lambrecht W, Schulte am Esch J. Source: Acta Anaesthesiologica Scandinavica. 1997 November; 41(10): 1312-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9422298

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Atypical presentation of malignant hyperthermia. Author(s): Evans TJ, Parent CM, McGunigal MP. Source: Anesthesiology. 2002 August; 97(2): 507-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151945

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Bayesian modeling of muscle biopsy contracture testing for malignant hyperthermia susceptibility. Author(s): Loke JC, MacLennan DH. Source: Anesthesiology. 1998 March; 88(3): 589-600. Erratum In: Anesthesiology 1998 August; 89(2): 555. Anesthesiology 1998 December; 89(6): 1615. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9523800

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Be alert for symptoms of malignant hyperthermia. Author(s): Edwards DB. Source: Dent Stud. 1977 June; 55(9): 33-4, 39. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=271097

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Between-center variability of results of the in vitro contracture test for malignant hyperthermia susceptibility. Author(s): Ording H, Islander G, Bendixen D, Ranklev-Twetman E. Source: Anesthesia and Analgesia. 2000 August; 91(2): 452-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10910867

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Birth defects and predisposition to malignant hyperthermia. Author(s): Pinsky L. Source: The Journal of Pediatrics. 1987 March; 110(3): 494. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3819954

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B-lymphocytes from malignant hyperthermia-susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators. Author(s): Girard T, Cavagna D, Padovan E, Spagnoli G, Urwyler A, Zorzato F, Treves S. Source: The Journal of Biological Chemistry. 2001 December 21; 276(51): 48077-82. Epub 2001 October 22. Erratum In: J Biol Chem 2002 April 19; 277(16): 14350. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673462

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Burkitt's lymphoma and malignant hyperthermia. Author(s): Flewellen EH. Source: Anesthesia and Analgesia. 1980 December; 59(12): 955. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7192518

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Burkitt's lymphoma: tumor lysis following malignant hyperthermia. Author(s): Suer RP, Fisher WB, Pearson RW, Triplett DA. Source: Cancer Treat Rep. 1980 February-March; 64(2-3): 327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7407766

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C1840-T mutation in the human skeletal muscle ryanodine receptor gene: frequency in northern German families susceptible to malignant hyperthermia and the relationship to in vitro contracture response. Author(s): Steinfath M, Singh S, Scholz J, Becker K, Lenzen C, Wappler F, Kochling A, Roewer N, Schulte am Esch J. Source: Journal of Molecular Medicine (Berlin, Germany). 1995 January; 73(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7633940

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Ca2+ inactivation, Mg2+ inhibition and malignant hyperthermia. Author(s): Lamb GD. Source: Journal of Muscle Research and Cell Motility. 1993 December; 14(6): 554-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8126214

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Caffeine and halothane sensitivity of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease. Author(s): Tong J, Oyamada H, Demaurex N, Grinstein S, McCarthy TV, MacLennan DH. Source: The Journal of Biological Chemistry. 1997 October 17; 272(42): 26332-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9334205

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Caffeine impairs intramuscular energy balance in patients susceptible to malignant hyperthermia. Author(s): Textor Z, Beer M, Anetseder M, Kostler H, Kagerbauer E, Kenn W, Hahn D, Roewer N. Source: Muscle & Nerve. 2003 September; 28(3): 353-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929196

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Charcot-Marie-Tooth disease--suxamethonium and malignant hyperthermia triggering agents. Author(s): Mills P. Source: Anaesthesia. 1998 November; 53(11): 1134. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10023294

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Chlorocresol, an additive to commercial succinylcholine, induces contracture of human malignant hyperthermia-susceptible muscles via activation of the ryanodine receptor Ca2+ channel. Author(s): Tegazzin V, Scutari E, Treves S, Zorzato F. Source: Anesthesiology. 1996 June; 84(6): 1380-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8669679

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Classification of malignant hyperthermia-equivocal patients by 4-chloro-M-cresol. Author(s): Gilly H, Musat I, Fricker R, Bittner RE, Steinbereithner K, Kress HG. Source: Anesthesia and Analgesia. 1997 July; 85(1): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9212139

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Clinical reassessment of malignant hyperthermia in Abitibi-Temiscamingue. Author(s): Bachand M, Vachon N, Boisvert M, Mayer FM, Chartrand D. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1997 July; 44(7): 696-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9232296

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Clinical variability of possible malignant hyperthermia as revealed by two cases. Author(s): Bendixen D, Poulsen TD, Knudsen F, Nielsen J, Ording H. Source: Acta Anaesthesiol Belg. 1994; 45(3): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7847043

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Comparison between the European and North American protocols for diagnosis of malignant hyperthermia susceptibility in humans. Author(s): Islander G, Twetman ER. Source: Anesthesia and Analgesia. 1999 May; 88(5): 1155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10320187

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Comparison of European and North American malignant hyperthermia diagnostic protocol outcomes for use in genetic studies. Author(s): Fletcher JE, Rosenberg H, Aggarwal M. Source: Anesthesiology. 1999 March; 90(3): 654-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078664

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Comparison of the segregation of the RYR1 C1840T mutation with segregation of the caffeine/halothane contracture test results for malignant hyperthermia susceptibility in a large Manitoba Mennonite family. Author(s): Serfas KD, Bose D, Patel L, Wrogemann K, Phillips MS, MacLennan DH, Greenberg CR. Source: Anesthesiology. 1996 February; 84(2): 322-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8602662

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Comparison of the segregation of the RYR1 C184OT mutation with segregation of the caffeine/halothane contracture test results for malignant hyperthermia susceptibility in a large Manitoba Mennonite family. Author(s): Hogan K. Source: Anesthesiology. 1996 February; 84(2): 29A-30A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8602659

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Complex pharmacology of malignant hyperthermia. Author(s): Pessah IN, Lynch C 3rd, Gronert GA. Source: Anesthesiology. 1996 June; 84(6): 1275-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8669666

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Concepts in the prevention and management of malignant hyperthermia. Author(s): Collins CP, Beirne OR. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 November; 61(11): 1340-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613092

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Congenital myopathy with central cores and fingerprint bodies in association with malignant hyperthermia susceptibility. Author(s): Stojkovic T, Maurage CA, Moerman A, Hurtevent JF, Krivosic-Horber R, Pellissier JF, Vermersch P. Source: Neuromuscular Disorders : Nmd. 2001 September; 11(6-7): 538-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11525882

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Continued puzzles in malignant hyperthermia. Author(s): Antognini JF, Gronert GA. Source: Journal of Clinical Anesthesia. 1997 February; 9(1): 1-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9051537

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Continuous veno-venous hemofiltration for the immediate management of massive rhabdomyolysis after fulminant malignant hyperthermia in a bodybuilder. Author(s): Schenk MR, Beck DH, Nolte M, Kox WJ. Source: Anesthesiology. 2001 June; 94(6): 1139-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11465608

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Control of calcium in skeletal muscle excitation-contraction coupling: implications for malignant hyperthermia. Author(s): Wingertzahn MA, Ochs RS. Source: Molecular Genetics and Metabolism. 1998 October; 65(2): 113-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9787103

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Creatine kinase alterations after acute malignant hyperthermia episodes and common surgical procedures. Author(s): Antognini JF. Source: Anesthesia and Analgesia. 1995 November; 81(5): 1039-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7486044

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Death caused by overheating in piglets susceptible to malignant hyperthermia. Author(s): Denborough M, Hopkinson KC. Source: The Medical Journal of Australia. 1994 June 6; 160(11): 731-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8202017

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Delayed onset of malignant hyperthermia in desflurane anesthesia. Author(s): Hoenemann CW, Halene-Holtgraeve TB, Booke M, Hinder F, Daudel F, Reich A, Van Aken H. Source: Anesthesia and Analgesia. 2003 January; 96(1): 165-7, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505945

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Delayed postoperative rhabdomyolysis in a patient subsequently diagnosed as malignant hyperthermia susceptible. Author(s): McKenney KA, Holman SJ. Source: Anesthesiology. 2002 March; 96(3): 764-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11873057

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Delayed recovery from muscle weakness due to malignant hyperthermia during sevoflurane anesthesia. Author(s): Maeda H, Iranami H, Hatano Y. Source: Anesthesiology. 1997 August; 87(2): 425-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9286908

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Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia. Author(s): Quane KA, Ording H, Keating KE, Manning BM, Heine R, Bendixen D, Berg K, Krivosic-Horber R, Lehmann-Horn F, Fagerlund T, McCarthy TV. Source: British Journal of Anaesthesia. 1997 September; 79(3): 332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9389851

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Detection of a novel mutation in the ryanodine receptor gene in an Irish malignant hyperthermia pedigree: correlation of the IVCT response with the affected and unaffected haplotypes. Author(s): Keating KE, Giblin L, Lynch PJ, Quane KA, Lehane M, Heffron JJ, McCarthy TV. Source: Journal of Medical Genetics. 1997 April; 34(4): 291-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9138151

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Detection of a novel ryanodine receptor subtype 1 mutation (R328W) in a malignant hyperthermia family by sequencing of a leukocyte transcript. Author(s): Loke JC, Kraev N, Sharma P, Du G, Patel L, Kraev A, MacLennan DH. Source: Anesthesiology. 2003 August; 99(2): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883402

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Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees. Author(s): Keating KE, Quane KA, Manning BM, Lehane M, Hartung E, Censier K, Urwyler A, Klausnitzer M, Muller CR, Heffron JJ, et al. Source: Human Molecular Genetics. 1994 October; 3(10): 1855-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7849712

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Detection of proton release from cultured human myotubes to identify malignant hyperthermia susceptibility. Author(s): Klingler W, Baur C, Georgieff M, Lehmann-Horn F, Melzer W. Source: Anesthesiology. 2002 November; 97(5): 1059-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12411787

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Determination of a positive malignant hyperthermia (MH) disposition without the in vitro contracture test in families carrying the RYR1 Arg614Cys mutation. Author(s): Rueffert H, Olthoff D, Deutrich C, Froster UG. Source: Clinical Genetics. 2001 August; 60(2): 117-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11553045

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Development of malignant hyperthermia post-cardiopulmonary bypass during surgery for mitral valve replacement. Author(s): Pandya AB, O'Leary CE. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2003 October; 17(5): 625-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579218

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Diagnosing malignant hyperthermia susceptibility. Author(s): Hopkins PM, Halsall PJ, Ellis FR. Source: Anaesthesia. 1994 May; 49(5): 373-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8209973

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Diagnosis of malignant hyperthermia susceptibility during CABG surgery. Author(s): Girard T, Bally S, Langer I, Schurch M. Source: Acta Anaesthesiologica Scandinavica. 2003 February; 47(2): 233-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631056

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Diagnosis of malignant hyperthermia: a comparison of the in vitro contracture test with the molecular genetic diagnosis in a large pedigree. Author(s): Healy JM, Quane KA, Keating KE, Lehane M, Heffron JJ, McCarthy TV. Source: Journal of Medical Genetics. 1996 January; 33(1): 18-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8825043

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Diagnosis of susceptibility to malignant hyperthermia by use of a metabolic test. Author(s): Anetseder M, Hager M, Muller CR, Roewer N. Source: Lancet. 2002 May 4; 359(9317): 1579-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047971

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Differential diagnosis of malignant hyperthermia. Author(s): LaPointe G. Source: Aana Journal. 1996 February; 64(1): 4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8928598

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Differential diagnosis of malignant hyperthermia: a case report. Author(s): Struebing VL. Source: Aana Journal. 1995 October; 63(5): 455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7502646

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Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation. Author(s): Fagerlund TH, Ording H, Bendixen D, Islander G, Ranklev Twetman E, Berg K. Source: Clinical Genetics. 1997 December; 52(6): 416-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9520251

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Discordance between phenotype and genotype in malignant hyperthermia. Author(s): MacLennan DH. Source: Current Opinion in Neurology. 1995 October; 8(5): 397-401. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8542047

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Discordance, in a malignant hyperthermia pedigree, between in vitro contracture-test phenotypes and haplotypes for the MHS1 region on chromosome 19q12-13.2, comprising the C1840T transition in the RYR1 gene. Author(s): Deufel T, Sudbrak R, Feist Y, Rubsam B, Du Chesne I, Schafer KL, Roewer N, Grimm T, Lehmann-Horn F, Hartung EJ, et al. Source: American Journal of Human Genetics. 1995 June; 56(6): 1334-42. Erratum In: Am J Hum Genet 1995 August; 57(2): 520. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7762556

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Early recognition of unsuspected malignant hyperthermia and successful management of serve myoglobinuric renal failure in subsequent rhabdomyolysis: a case report. Author(s): Lee CH, Lam KK, Fung ST, Lee CT, Hsu KT. Source: Changgeng Yi Xue Za Zhi. 1998 June; 21(2): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9729658

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Educational computer simulation of malignant hyperthermia. Author(s): Schwid HA, O'Donnell D. Source: Journal of Clinical Monitoring. 1992 July; 8(3): 201-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1494926

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Effect of cocaine on the contracture response to 1% halothane in patients undergoing diagnostic muscle biopsy for malignant hyperthermia. Author(s): Sato N, Brum JM, Mitsumoto H, DeBoer GE. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1995 February; 42(2): 158-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7720160

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Effects of halothane on mechanical response of skeletal muscle from malignant hyperthermia susceptible patients. Author(s): Etchrivi TS, Adnet PJ, Tavernier B, Diallo A, Haudecoeur G, Krivosic-Horber RM. Source: Archives of Physiology and Biochemistry. 1998 October; 106(4): 318-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417859

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Effects of Mg(2+) and SR luminal Ca(2+) on caffeine-induced Ca(2+) release in skeletal muscle from humans susceptible to malignant hyperthermia. Author(s): Duke AM, Hopkins PM, Steele DS. Source: The Journal of Physiology. 2002 October 1; 544(Pt 1): 85-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356882

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Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients. Author(s): Fiege M, Wappler F, Scholz J, Weisshorn R, von Richthofen V, Schulte am Esch J. Source: Journal of Clinical Anesthesia. 2000 March; 12(2): 123-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10818326

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Effects of the serotonin2 receptor agonist DOI on skeletal muscle specimens from malignant hyperthermia-susceptible patients. Author(s): Wappler F, Roewer N, Kochling A, Scholz J, Loscher W, Steinfath M. Source: Anesthesiology. 1996 June; 84(6): 1280-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8669667

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Effects of three different types of management on the elimination kinetics of volatile anaesthetics. Implications for malignant hyperthermia treatment. Author(s): Reber A, Schumacher P, Urwyler A. Source: Anaesthesia. 1993 October; 48(10): 862-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8238827

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Electrodiagnostic tests in the detection of malignant hyperthermia. Author(s): Eng GD, Becker MJ, Muldoon SM. Source: Muscle & Nerve. 1984 October; 7(8): 618-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6543907

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Elimination of hypercapnia may postpone the clinical presentation of malignant hyperthermia: a case report. Author(s): Chia YY, Liu YC, Lee MC, Lo Y, Liu K. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1998 April; 61(4): 230-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9614782

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Emergency! Malignant hyperthermia. Author(s): Vermette E. Source: The American Journal of Nursing. 1998 April; 98(4): 45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9556683

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Evaluation of anaesthesias in malignant hyperthermia negative patients. Author(s): Islander G, Ranklev-Twetman E. Source: Acta Anaesthesiologica Scandinavica. 1995 August; 39(6): 819-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7484041

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Evaluation of spin resonance spectroscopy of red blood cell membranes to detect malignant hyperthermia susceptibility. Author(s): Halsall PJ, Ellis FR, Knowles PF. Source: British Journal of Anaesthesia. 1992 November; 69(5): 471-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1334685

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Evidence for a spontaneous C1840-T mutation in the RYR1 gene after DNA fingerprinting in a malignant hyperthermia susceptible family. Author(s): Steinfath M, Seranski P, Singh S, Fiege M, Wappler F, Schulte Am Esch J, Scholz J. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2002 October; 366(4): 372-5. Epub 2002 July 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12237752

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Evidence for genetic heterogeneity of malignant hyperthermia susceptibility. Author(s): Deufel T, Golla A, Iles D, Meindl A, Meitinger T, Schindelhauer D, DeVries A, Pongratz D, MacLennan DH, Johnson KJ, et al. Source: American Journal of Human Genetics. 1992 June; 50(6): 1151-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1598899

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Evidence for susceptibility to malignant hyperthermia in patients with exerciseinduced rhabdomyolysis. Author(s): Wappler F, Fiege M, Steinfath M, Agarwal K, Scholz J, Singh S, Matschke J, Schulte Am Esch J. Source: Anesthesiology. 2001 January; 94(1): 95-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11135728

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Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q. Author(s): Levitt RC, Olckers A, Meyers S, Fletcher JE, Rosenberg H, Isaacs H, Meyers DA. Source: Genomics. 1992 November; 14(3): 562-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1427885

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Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia. Author(s): O'Brien RO, Taske NL, Hansbro PM, Matthaei KI, Hogan SP, Denborough MA, Foster PS. Source: Journal of Medical Genetics. 1995 November; 32(11): 913-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8592342

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Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha 1, beta 1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect. Author(s): Sudbrak R, Golla A, Hogan K, Powers P, Gregg R, Du Chesne I, LehmannHorn F, Deufel T. Source: Human Molecular Genetics. 1993 July; 2(7): 857-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8395939

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Extending the skeletal muscle viability period in the malignant hyperthermia test. Author(s): Bina S, Holman S, Muldoon SM. Source: Anesthesia and Analgesia. 2003 January; 96(1): 153-8, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505942

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Factitious halothane detection during trigger-free anesthesia in a malignant hyperthermia susceptible patient. Author(s): Hawkes CA. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 June; 46(6): 567-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10391605

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Failure of the platelet-halothane nucleotide depletion test as a diagnostic or screening test for malignant hyperthermia. Author(s): Britt BA, Scott EA. Source: Anesthesia and Analgesia. 1986 February; 65(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3942305

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Failure of the tourniquet-twitch test as a diagnostic or screening test for malignant hyperthermia. Author(s): Britt BA, Scott EA, Kleiman A, Jones P, Steward DJ. Source: Anesthesia and Analgesia. 1986 October; 65(10): 1047-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3752552

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Failure to identify the ryanodine receptor G1021A mutation in a large North American population with malignant hyperthermia. Author(s): Stewart SL, Rosenberg H, Fletcher JE. Source: Clinical Genetics. 1998 October; 54(4): 358-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9831351

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False-negative results with muscle caffeine halothane contracture testing for malignant hyperthermia. Author(s): Isaacs H, Badenhorst M. Source: Anesthesiology. 1993 July; 79(1): 5-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8342829

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Fatal inherited rhabdomyolysis and malignant hyperthermia. Author(s): Denborough MA, McLean A, Morgan G, Hopkinson KC. Source: Lancet. 1994 January 22; 343(8891): 236-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7904690

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Fatal malignant hyperthermia as a result of ingestion of tranylcypromine (Parnate) combined with white wine and cheese. Author(s): Mirchandani H, Reich LE. Source: J Forensic Sci. 1985 January; 30(1): 217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3981112

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Fatal malignant hyperthermia associated with recreational cocaine and ethanol abuse. Author(s): Loghmanee F, Tobak M. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1986 September; 7(3): 246-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3788915

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Fatal malignant hyperthermia--delayed onset and atypical course. Author(s): Karger B, Teige K. Source: Forensic Science International. 2002 October 9; 129(3): 187-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372688

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Fatal malignant hyperthermia-like syndrome with rhabdomyolysis complicating the presentation of diabetes mellitus in adolescent males. Author(s): Hollander AS, Olney RC, Blackett PR, Marshall BA. Source: Pediatrics. 2003 June; 111(6 Pt 1): 1447-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777570

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Fatal side-effects of continuous propofol infusion in children may be related to malignant hyperthermia. Author(s): Plotz FB, Waalkens HJ, Verkade HJ, Strengers JL, Knoester H, Mandema JM. Source: Anaesthesia and Intensive Care. 1996 December; 24(6): 724. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8971326

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Fatty acids markedly lower the threshold for halothane-induced calcium release from the terminal cisternae in human and porcine normal and malignant hyperthermia susceptible skeletal muscle. Author(s): Fletcher JE, Mayerberger S, Tripolitis L, Yudkowsky M, Rosenberg H. Source: Life Sciences. 1991; 49(22): 1651-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1943469

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Fatty acids modulate calcium-induced calcium release from skeletal muscle heavy sarcoplasmic reticulum fractions: implications for malignant hyperthermia. Author(s): Fletcher JE, Tripolitis L, Erwin K, Hanson S, Rosenberg H, Conti PA, Beech J. Source: Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 1990 October; 68(10): 1195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2125224

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Femoral block with mepivacaine for muscle biopsy in malignant hyperthermia patients. Author(s): Berkowitz A, Rosenberg H. Source: Anesthesiology. 1985 May; 62(5): 651-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3994033

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Fiber-type caffeine sensitivities in skinned muscle fibers from humans susceptible to malignant hyperthermia. Author(s): Adnet PJ, Bromberg NL, Haudecoeur G, Krivosic I, Adamantidis MM, Reyford H, Bello N, Krivosic Horber RM. Source: Anesthesiology. 1993 January; 78(1): 168-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8424551

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Fluidity state of lymphocyte plasma membrane in malignant hyperthermia susceptible pigs and humans. Author(s): Rock E, Motta C, Vignon X, Kozak-Ribbens G. Source: Acta Anaesthesiologica Scandinavica. 1993 July; 37(5): 488-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8356862

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Fluoxetine treatment of a depressed patient susceptible to malignant hyperthermia. Author(s): Burket RC, Hodgin JD. Source: The American Journal of Psychiatry. 1989 May; 146(5): 680. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2785349

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Free radicals and calcium homeostasis: relevance to malignant hyperthermia? Author(s): Duthie GG, Arthur JR. Source: Free Radical Biology & Medicine. 1993 April; 14(4): 435-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8468027

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Fulminant malignant hyperthermia associated with ketoacidotic diabetic coma. Author(s): Wappler F, Roewer N, Kochling A, Braune H, Reissinger T, Schulte am Esch J. Source: Intensive Care Medicine. 1996 August; 22(8): 809-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8880251

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Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle. Author(s): Richter M, Schleithoff L, Deufel T, Lehmann-Horn F, Herrmann-Frank A. Source: The Journal of Biological Chemistry. 1997 February 21; 272(8): 5256-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9030597

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General anesthesia in a malignant hyperthermia susceptible patient. Author(s): Jones JE, Dierdorf SF, Clapp DW. Source: J Oral Med. 1987 January-March; 42(1): 22-4, 66. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2950215

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General pediatric emergencies. Malignant hyperthermia syndrome. Author(s): Hall SC. Source: Anesthesiology Clinics of North America. 2001 June; 19(2): 367-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469069

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Genetic analysis with calcium-induced calcium release test in Japanese malignant hyperthermia susceptible (MHS) families. Author(s): Maehara Y, Mukaida K, Hiyama E, Morio M, Kawamoto M, Yuge O. Source: Hiroshima J Med Sci. 1999 March; 48(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10213958

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Genetic heterogeneity and HOMOG analysis in British malignant hyperthermia families. Author(s): Robinson R, Curran JL, Hall WJ, Halsall PJ, Hopkins PM, Markham AF, Stewart AD, West SP, Ellis FR. Source: Journal of Medical Genetics. 1998 March; 35(3): 196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9541102

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Genetic linkage analysis of chromosome 19 markers in malignant hyperthermia. Author(s): Ball SP, Dorkins HR, Ellis FR, Hall JL, Halsall PJ, Hopkins PM, Mueller RF, Stewart AD. Source: British Journal of Anaesthesia. 1993 January; 70(1): 70-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8431338

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Genetic mapping of the beta 1- and gamma-subunits of the human skeletal muscle Ltype voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility. Author(s): Iles DE, Segers B, Sengers RC, Monsieurs K, Heytens L, Halsall PJ, Hopkins PM, Ellis FR, Hall-Curran JL, Stewart AD, et al. Source: Human Molecular Genetics. 1993 July; 2(7): 863-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8395940

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Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle. Author(s): Fagerlund T, Islander G, Ranklev E, Harbitz I, Hauge JG, Mokleby E, Berg K. Source: Clinical Genetics. 1992 May; 41(5): 270-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1318804

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Genetic testing for malignant hyperthermia in North America. Author(s): Nelson TE, Rosenberg H, Muldoon SM. Source: Anesthesiology. 2004 February; 100(2): 212-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739790

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Genetics and pathogenesis of malignant hyperthermia. Author(s): Jurkat-Rott K, McCarthy T, Lehmann-Horn F. Source: Muscle & Nerve. 2000 January; 23(1): 4-17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10590402

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Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia. Author(s): Fletcher JE, Tripolitis L, Hubert M, Vita GM, Levitt RC, Rosenberg H. Source: British Journal of Anaesthesia. 1995 September; 75(3): 307-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547049

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Genotype-phenotype comparison of the Swiss malignant hyperthermia population. Author(s): Girard T, Urwyler A, Censier K, Mueller CR, Zorzato F, Treves S. Source: Human Mutation. 2001 October; 18(4): 357-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668625

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Gly341Arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity. Author(s): Monsieurs KG, Van Broeckhoven C, Martin JJ, Van Hoof VO, Heytens L. Source: Journal of the Neurological Sciences. 1998 January 21; 154(1): 62-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9543323

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Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Author(s): Urwyler A, Deufel T, McCarthy T, West S; European Malignant Hyperthermia Group. Source: British Journal of Anaesthesia. 2001 February; 86(2): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573677

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Guidelines for the use of local anesthetics in the dental treatment of patients who are susceptible to malignant hyperthermia. Author(s): D'Ambrosio J, Adragna MG. Source: Spec Care Dentist. 1988 March-April; 8(2): 61-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2978768

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Halothane concentrations for malignant hyperthermia testing. Author(s): Johnsen RD. Source: Acta Anaesthesiologica Scandinavica. 1994 January; 38(1): 89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8140881

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Halothane effects on human malignant hyperthermia skeletal muscle single calciumrelease channels in planar lipid bilayers. Author(s): Nelson TE. Source: Anesthesiology. 1992 April; 76(4): 588-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1312798

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Halothane stimulates the aggregation of platelets of both normal individuals and those susceptible to malignant hyperthermia. Author(s): Gerrard JM, Duncan PG, Koshyk SA, Glover SM, McCrea JM. Source: British Journal of Anaesthesia. 1983 December; 55(12): 1249-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6652014

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Halothane-dependent release of intracellular Ca2+ in blood cells in malignant hyperthermia. Author(s): Klip A, Mills GB, Britt BA, Elliott ME. Source: The American Journal of Physiology. 1990 March; 258(3 Pt 1): C495-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2107750

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Halothane-induced calcium release in cultured human skeletal muscle cells from a family susceptible to malignant hyperthermia with an unidentified mutation in chromosome 19. Author(s): Snoeck MM, Oosterhof A, Tangerman A, Veerkamp JH, van Engelen BG, Gielen MJ. Source: Anesthesiology. 2002 July; 97(1): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131133

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Halothane-succinylcholine induced masseter spasm: indicative of malignant hyperthermia susceptibility? Author(s): Flewellen EH, Nelson TE. Source: Anesthesia and Analgesia. 1984 July; 63(7): 693-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6731899

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Haplotype analysis of the BYR1 gene in malignant hyperthermia and central core disease. Author(s): Quane KA, Keating KE, Healy JM, Heffron JJ, Lehane M, Krivosic-Horber R, Heytens L, McCarthy TV. Source: Biochemical Society Transactions. 1995 May; 23(2): 372S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7672403

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Heat production during anesthetic-induced malignant hyperthermia. Author(s): Nelson TE. Source: Bioscience Reports. 2001 April; 21(2): 169-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11725865

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Hemodynamic and metabolic alterations in response to graded exercise in a patient susceptible to malignant hyperthermia. Author(s): Wappler F, Fiege M, Antz M, Schulte am Esch J. Source: Anesthesiology. 2000 January; 92(1): 268-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10638927

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High-purity ryanodine and 9,21-dehydroryanodine for in vitro diagnosis of malignant hyperthermia in man. Author(s): Wappler F, Roewer N, Lenzen C, Kochling A, Scholz J, Steinfath M, Schulte am Esch J. Source: British Journal of Anaesthesia. 1994 February; 72(2): 240-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8110584

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High-resolution physical mapping of four microsatellite repeat markers near the RYR1 locus on chromosome 19q13.1 and apparent exclusion of the MHS locus from this region in two malignant hyperthermia susceptible families. Author(s): Iles DE, Segers B, Heytens L, Sengers RC, Wieringa B. Source: Genomics. 1992 November; 14(3): 749-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1427902

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Histological support for the difference between malignant hyperthermia susceptible (MHS), equivocal (MHE) and negative (MHN) muscle biopsies. Author(s): Mezin P, Payen JF, Bosson JL, Brambilla E, Stieglitz P. Source: British Journal of Anaesthesia. 1997 September; 79(3): 327-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9389850

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Histomorphologic examination of skeletal muscle preparations does not differentiate between malignant hyperthermia-susceptible and -normal patients. Author(s): von Breunig F, Wappler F, Hagel C, von Richthofen V, Fiege M, Weisshorn R, Stavrou D, Schulte am Esch J. Source: Anesthesiology. 2004 April; 100(4): 789-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15087612

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Homozygous and heterozygous Arg614Cys mutations (1840C-->T) in the ryanodine receptor gene co-segregate with malignant hyperthermia susceptibility in a German family. Author(s): Rueffert H, Olthoff D, Deutrich C, Thamm B, Froster UG. Source: British Journal of Anaesthesia. 2001 August; 87(2): 240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11493496

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How carefully can we phenotype patients suspected of malignant hyperthermia susceptibility? Author(s): Larach MG, MacLennan DH. Source: Anesthesiology. 1999 March; 90(3): 645-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078661

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How do anaesthesiologists treat malignant hyperthermia in a full-scale anaesthesia simulator? Author(s): i Gardi T, Christensen UC, Jacobsen J, Jensen PF, Ording H. Source: Acta Anaesthesiologica Scandinavica. 2001 September; 45(8): 1032-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576057

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How much dantrolene? A case of fulminant malignant hyperthermia. Author(s): Cain AG, Bell AD. Source: Anaesthesia and Intensive Care. 1989 November; 17(4): 500-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2596684

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Human malignant hyperthermia associated with desflurane anesthesia. Author(s): Allen GC, Brubaker CL. Source: Anesthesia and Analgesia. 1998 June; 86(6): 1328-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9620529

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Hypersensitive response of malignant hyperthermia-susceptible skeletal muscle to inositol 1,4,5-triphosphate induced release of calcium. Author(s): Lopez JR, Perez C, Linares N, Allen P, Terzic A. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1995 October; 352(4): 442-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8532074

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Hypokalemic periodic paralysis associated with malignant hyperthermia. Author(s): Rajabally YA, El Lahawi M. Source: Muscle & Nerve. 2002 March; 25(3): 453-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870726

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Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families. Author(s): Sambuughin N, Nelson TE, Jankovic J, Xin C, Meissner G, Mullakandov M, Ji J, Rosenberg H, Sivakumar K, Goldfarb LG. Source: Neuromuscular Disorders : Nmd. 2001 September; 11(6-7): 530-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11525881

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Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation. Author(s): Manning BM, Quane KA, Ording H, Urwyler A, Tegazzin V, Lehane M, O'Halloran J, Hartung E, Giblin LM, Lynch PJ, Vaughan P, Censier K, Bendixen D, Comi G, Heytens L, Monsieurs K, Fagerlund T, Wolz W, Heffron JJ, Muller CR, McCarthy TV. Source: American Journal of Human Genetics. 1998 March; 62(3): 599-609. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9497245

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Improved noninvasive diagnostic testing for malignant hyperthermia susceptibility from a combination of metabolites determined in vivo with 31P-magnetic resonance spectroscopy. Author(s): Payen JF, Bosson JL, Bourdon L, Jacquot C, Le Bas JF, Stieglitz P, Benabid AL. Source: Anesthesiology. 1993 May; 78(5): 848-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8489056

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In vitro 31P-magnetic resonance spectroscopy of muscle extracts in malignant hyperthermia-susceptible patients. Author(s): Payen JF, Fouilhe N, Sam-Lai E, Remy C, Dupeyre R, Mezin P, Halsall J, Stieglitz P. Source: Anesthesiology. 1996 May; 84(5): 1077-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8624001

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In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group. Author(s): Ording H, Brancadoro V, Cozzolino S, Ellis FR, Glauber V, Gonano EF, Halsall PJ, Hartung E, Heffron JJ, Heytens L, Kozak-Ribbens G, Kress H, KrivosicHorber R, Lehmann-Horn F, Mortier W, Nivoche Y, Ranklev-Twetman E, Sigurdsson S, Snoeck M, Stieglitz P, Tegazzin V, Urwyler A, Wappler F. Source: Acta Anaesthesiologica Scandinavica. 1997 September; 41(8): 955-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9311391

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In vitro diagnosis of malignant hyperthermia susceptibility with ryanodine-induced contractures in human skeletal muscles. Author(s): Wappler F, Roewer N, Kochling A, Scholz J, Steinfath M, Schulte am Esch J. Source: Anesthesia and Analgesia. 1996 June; 82(6): 1230-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8638796

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In vitro effect of ephedrine, adrenaline, noradrenaline and isoprenaline on halothaneinduced contractures in skeletal muscle from patients potentially susceptible to malignant hyperthermia. Author(s): Urwyler A, Censier K, Seeberger MD, Rothenbuhler JM, Kaufmann MA, Drewe J. Source: British Journal of Anaesthesia. 1993 January; 70(1): 76-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8431339

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Incidence of malignant hyperthermia reactions in 2,214 patients undergoing muscle biopsy. Author(s): Carr AS, Lerman J, Cunliffe M, McLeod ME, Britt BA. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1995 April; 42(4): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7788824

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Increased sensitivity of the ryanodine receptor to halothane-induced oligomerization in malignant hyperthermia-susceptible human skeletal muscle. Author(s): Glover L, Heffron JJ, Ohlendieck K. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2004 January; 96(1): 11-8. Epub 2003 September 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959958

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Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation. Author(s): Wehner M, Rueffert H, Koenig F, Neuhaus J, Olthoff D. Source: Clinical Genetics. 2002 August; 62(2): 135-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220451

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Index of suspicion. Case 2. Diagnosis: malignant hyperthermia. Author(s): Gutierrez LD. Source: Pediatrics in Review / American Academy of Pediatrics. 1996 August; 17(8): 291, 293. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8927582

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Inositol 1,4,5-trisphosphate in blood and skeletal muscle in human malignant hyperthermia. Author(s): Wappler F, Scholz J, Kochling A, Steinfath M, Krause T, Schulte am Esch J. Source: British Journal of Anaesthesia. 1997 May; 78(5): 541-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9175969

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Intolerance to neuroleptics and susceptibility for malignant hyperthermia in a patient with proximal myotonic myopathy (PROMM) and schizophrenia. Author(s): Schneider C, Pedrosa Gil F, Schneider M, Anetseder M, Kress W, Muller CR. Source: Neuromuscular Disorders : Nmd. 2002 January; 12(1): 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731282

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Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia-susceptible and normal individuals. Effect Of overexpression of recombinant wild-type and Arg163Cys mutated ryanodine receptors. Author(s): Censier K, Urwyler A, Zorzato F, Treves S. Source: The Journal of Clinical Investigation. 1998 March 15; 101(6): 1233-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9502764

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Intraoperative hyperkalemia as a triggering mechanism or presenting sign of malignant hyperthermia in two patients with chronic renal failure. Author(s): Sprung J, DeBoer G, Zanettin G, Ebrahim Z, Ryckman J, Kalhan S, Otto D. Source: Anesthesiology. 1995 June; 82(6): 1518-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7793665

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Investigation of malignant hyperthermia susceptibility in Denmark. Author(s): Ording H. Source: Dan Med Bull. 1996 April; 43(2): 111-25. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8741205

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Is desflurane a "weak" trigger of malignant hyperthermia? Author(s): Wappler F, Fiege M. Source: Anesthesia and Analgesia. 2003 July; 97(1): 295; Author Reply 295. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818992

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Is neuroleptic malignant syndrome a neurogenic form of malignant hyperthermia? Author(s): Gurrera RJ. Source: Clinical Neuropharmacology. 2002 July-August; 25(4): 183-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151905

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Is the "K-type" caffeine-halothane responder susceptible to malignant hyperthermia? Author(s): Ellis FR, Halsall PJ, Hopkins PM. Source: British Journal of Anaesthesia. 1992 November; 69(5): 468-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1467078

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Isolated masseter muscle spasm and increased creatine kinase without malignant hyperthermia susceptibility or other myopathies. Author(s): Kaplan RF, Rushing E. Source: Anesthesiology. 1992 October; 77(4): 820-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1416181

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King's syndrome with malignant hyperthermia. Potential outpatient risks. Author(s): Steenson AJ, Torkelson RD. Source: Am J Dis Child. 1987 March; 141(3): 271-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3812408

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Letter: Body temperature and malignant hyperthermia. Author(s): Lucke JN, Hall GM, Lister D. Source: Lancet. 1976 June 26; 1(7974): 1405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=59036

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Letter: Chronic viral myopathy and malignant hyperthermia. Author(s): Schiller HH. Source: The New England Journal of Medicine. 1975 June 26; 292(26): 1409. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1138175

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Letter: Malignant hyperthermia. Author(s): Flewellen EH. Source: Jama : the Journal of the American Medical Association. 1976 May 3; 235(18): 1967. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=946505

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Letter: Malignant hyperthermia: a human and procine stress syndrome? Author(s): Lister D, Hall GM, Lucke JN. Source: Lancet. 1975 March 1; 1(7905): 519. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=46983

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Letter: Malignant hyperthermia: a human stress syndrome? Author(s): Wingard DW. Source: Lancet. 1974 December 14; 2(7894): 1450-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4140360

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Letter: Preoperative excitement and malignant hyperthermia. Author(s): Mogensen JV, Misfeldt BB, Hanel HK. Source: Lancet. 1974 March 16; 1(7855): 461. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4131470

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Letter: Procaine and malignant hyperthermia. Author(s): Hoivik B, Stovner J. Source: Lancet. 1975 July 26; 2(7926): 185. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=49781

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Letter: Procaine and malignant hyperthermia. Author(s): MacLachlan D, Forrest AL. Source: Lancet. 1974 March 2; 1(7853): 355. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4131196

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Letter: Procaine for malignant hyperthermia. Author(s): Giosa N. Source: The New England Journal of Medicine. 1975 April 17; 292(16): 869-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1113822

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Letter: Procaine for malignant hyperthermia. Author(s): Heffron JJ, Mitchell G. Source: The New England Journal of Medicine. 1975 January 30; 292(5): 266-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1110700

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Letter: Procaine for malignant hyperthermia. Author(s): Benumof J. Source: The New England Journal of Medicine. 1974 July 25; 291(4): 209-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4834497

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Letter: Treatment of idiopathic malignant hyperthermia. Author(s): Saviello GM. Source: Archives of Ophthalmology. 1976 May; 94(5): 867. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1267662

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Lidocaine a safe agent to use for dysrhythmias during a malignant hyperthermia crisis. Author(s): Odom J. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 1991 MayJune; 10(3): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2052415

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Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree. Author(s): Moslehi R, Langlois S, Yam I, Friedman JM. Source: American Journal of Medical Genetics. 1998 February 26; 76(1): 21-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9508059

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Local anesthesia and malignant hyperthermia: review of the literature and recommendations for the dermatologic surgeon. Author(s): Murray C, Sasaki SS, Berg D. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 August; 25(8): 626-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10491046

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Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltagedependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. Author(s): Iles DE, Lehmann-Horn F, Scherer SW, Tsui LC, Olde Weghuis D, Suijkerbuijk RF, Heytens L, Mikala G, Schwartz A, Ellis FR, et al. Source: Human Molecular Genetics. 1994 June; 3(6): 969-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7951247

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Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2. Author(s): McCarthy TV, Healy JM, Heffron JJ, Lehane M, Deufel T, Lehmann-Horn F, Farrall M, Johnson K. Source: Nature. 1990 February 8; 343(6258): 562-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2300206

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Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-q13.2. Author(s): Healy JM, Lehane M, Heffron JJ, Farrell M, Johnson K, McCarthy TV. Source: Biochemical Society Transactions. 1990 April; 18(2): 326. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2379741

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Low molecular weight proteins in human malignant hyperthermia muscle. Author(s): Fletcher JE, Rosenberg H. Source: Anesthesiology. 1985 June; 62(6): 849-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4003830

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Lower limb compartment syndrome resulting from malignant hyperthermia. Author(s): Johnson IA, Andrzejowski JC, Currie JS. Source: Anaesthesia and Intensive Care. 1999 June; 27(3): 292-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10389565

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Malignant hyperthermia and myotonic disorders. Author(s): Rosenbaum HK, Miller JD. Source: Anesthesiology Clinics of North America. 2002 September; 20(3): 623-664. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12298310

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Malignant hyperthermia and the otolaryngologist. Author(s): Chang CY, Scher RL. Source: Ear, Nose, & Throat Journal. 2003 June; 82(6): 433-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861868

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Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees. Author(s): Davis M, Brown R, Dickson A, Horton H, James D, Laing N, Marston R, Norgate M, Perlman D, Pollock N, Stowell K. Source: British Journal of Anaesthesia. 2002 April; 88(4): 508-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12066726

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Malignant hyperthermia genetic testing in North America Working Group Meeting. Bethesda, Maryland. September 4-5, 2002. Author(s): Sei Y, Sambuughin N, Muldoon S. Source: Anesthesiology. 2004 February; 100(2): 464-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14870754

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Malignant hyperthermia in an adult trauma patient. Author(s): Elster EA, Harrison J, Stasiewicz SD, Wang D, Golocovsky M. Source: The American Surgeon. 2002 October; 68(10): 883-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412715

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Malignant hyperthermia. Author(s): Nasir KK, Zafar AB, Mansoor F, Mushtaq S, Ahmad J, Khan IM. Source: J Coll Physicians Surg Pak. 2004 January; 14(1): 39-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764260

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Malignant hyperthermia. Author(s): Ali SZ, Taguchi A, Rosenberg H. Source: Best Pract Res Clin Anaesthesiol. 2003 December; 17(4): 519-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14661655

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Malignant hyperthermia. Author(s): Halliday NJ. Source: The Journal of Craniofacial Surgery. 2003 September; 14(5): 800-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501352

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Malignant hyperthermia: a pharmacogenetic disease of Ca++ regulating proteins. Author(s): Nelson TE. Source: Current Molecular Medicine. 2002 June; 2(4): 347-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108947

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Malignant hyperthermia: clinical features and management. Author(s): Pritchard MJ. Source: Nurs Times. 2003 June 10-16; 99(23): 32-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838644

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Malignant hyperthermia: considerations for the general surgeon. Author(s): Heggie JE. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2002 October; 45(5): 369-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387544

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Malignant hyperthermia: how to spot it early. Author(s): Haslego SS. Source: Rn. 2002 July; 65(7): 31-5; Quiz 36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12136527

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Malignant hyperthermia--patients don't always read the textbook. Author(s): Wimbush S, Homewood J. Source: Anaesthesia. 2003 December; 58(12): 1245-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705708

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Molecular genetic testing for malignant hyperthermia susceptibility. Author(s): Girard T, Treves S, Voronkov E, Siegemund M, Urwyler A. Source: Anesthesiology. 2004 May; 100(5): 1076-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114203

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Multicentre evaluation of in vitro contracture testing with bolus administration of 4chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility. Author(s): Wappler F, Anetseder M, Baur CP, Censier K, Doetsch S, Felleiter P, Fiege M, Fricker R, Halsall PJ, Hartung E, Heffron JJ, Heytens L, Hopkins PM, Klingler W, Lehmann-Horn F, Nivoche Y, Tegazzin V, Tzanova I, Urwyler A, Weisshorn R, Schulte am Esch J. Source: European Journal of Anaesthesiology. 2003 July; 20(7): 528-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884985

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Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization. Author(s): Guis S, Figarella-Branger D, Monnier N, Bendahan D, Kozak-Ribbens G, Mattei JP, Lunardi J, Cozzone PJ, Pellissier JF. Source: Archives of Neurology. 2004 January; 61(1): 106-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732627

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Multiminicore myopathy, central core disease, malignant hyperthermia susceptibility, and RYR1 mutations: one disease with many faces? Author(s): Mathews KD, Moore SA. Source: Archives of Neurology. 2004 January; 61(1): 27-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732615

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Muscle biopsy for malignant hyperthermia testing can be scheduled and performed in 6 weeks. Author(s): Rosenbaum HK. Source: Anesthesia and Analgesia. 2003 November; 97(5): 1549; Author Reply 1549. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570697

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Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia. Author(s): Marchant CL, Ellis FR, Halsall PJ, Hopkins PM, Robinson RL. Source: Muscle & Nerve. 2004 July; 30(1): 114-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15221887

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Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region. Author(s): Galli L, Orrico A, Cozzolino S, Pietrini V, Tegazzin V, Sorrentino V. Source: Cell Calcium. 2002 September; 32(3): 143-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208234

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Neuroleptic malignant syndrome and malignant hyperthermia susceptibility. Author(s): Tweed WA. Source: Acta Anaesthesiologica Scandinavica. 1990 October; 34(7): 605. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2244451

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Neuroleptic malignant syndrome and malignant hyperthermia. Author(s): Wijeratne C. Source: The Australian and New Zealand Journal of Psychiatry. 1996 December; 30(6): 874. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9034482

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Neuroleptic malignant syndrome and malignant hyperthermia. Author(s): Caroff SN, Mann SC. Source: Anaesthesia and Intensive Care. 1993 August; 21(4): 477-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8214562

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Neuroleptic malignant syndrome and malignant hyperthermia. Author(s): Caroff S, Rosenberg H, Gerber JC. Source: Journal of Clinical Psychopharmacology. 1983 April; 3(2): 120-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6132930

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Neuroleptic malignant syndrome and malignant hyperthermia. Important issues for the medical consultant. Author(s): Heiman-Patterson TD. Source: The Medical Clinics of North America. 1993 March; 77(2): 477-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8095087

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Neuroleptic malignant syndrome and malignant hyperthermia. In vitro comparison with halothane and caffeine contracture tests. Author(s): Krivosic-Horber R, Adnet P, Guevart E, Theunynck D, Lestavel P. Source: British Journal of Anaesthesia. 1987 December; 59(12): 1554-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3426910

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Neuroleptic malignant syndrome and malignant hyperthermia: end of a controversy? Author(s): Keck PE Jr, Caroff SN, McElroy SL. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1995 Spring; 7(2): 135-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7626956

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Neuroleptic malignant syndrome versus malignant hyperthermia. Author(s): Hard C. Source: The American Journal of Medicine. 1991 September; 91(3): 322-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1892158

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Nitroglycerin for fetal surgery: fetoscopy and ex utero intrapartum treatment procedure with malignant hyperthermia precautions. Author(s): Rosen MA, Andreae MH, Cameron AG. Source: Anesthesia and Analgesia. 2003 March; 96(3): 698-700, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598248

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No association between the neuroleptic malignant syndrome and mutations in the RYR1 gene associated malignant hyperthermia. Author(s): Miyatake R, Iwahashi K, Matsushita M, Nakamura K, Suwaki H. Source: Journal of the Neurological Sciences. 1996 November; 143(1-2): 161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8981316

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No C1840 to T mutation in RYR1 in malignant hyperthermia. Author(s): Hall-Curran JL, Stewart AD, Ball SP, Halsall JP, Hopkins PM, Ellis FR. Source: Human Mutation. 1993; 2(4): 330. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8401544

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No evidence of mutations in the CACNA1S gene in the UK malignant hyperthermia population. Author(s): Brooks C, Robinson RL, Halsall PJ, Hopkins PM. Source: British Journal of Anaesthesia. 2002 April; 88(4): 587-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12066739

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No myocardial involvement in nonrigid malignant hyperthermia. Author(s): Kawamoto M, Yuge O, Kikuchi H, Kodama K, Morio M. Source: Anesthesiology. 1986 January; 64(1): 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3942340

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No relationship between fiber type and halothane contracture test results in malignant hyperthermia. Author(s): Heiman-Patterson T, Fletcher JE, Rosenberg H, Tahmoush AJ. Source: Anesthesiology. 1987 July; 67(1): 82-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2440353

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No response to trigger agents in a malignant hyperthermia-susceptible patient. Author(s): Claxton BA, Cross MH, Hopkins PM. Source: British Journal of Anaesthesia. 2002 June; 88(6): 870-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173209

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North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations. Author(s): Sambuughin N, Sei Y, Gallagher KL, Wyre HW, Madsen D, Nelson TE, Fletcher JE, Rosenberg H, Muldoon SM. Source: Anesthesiology. 2001 September; 95(3): 594-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575529

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Novel mutation in the RYR1 gene (R2454C) in a patient with malignant hyperthermia. Author(s): Gencik M, Gencik A, Mortier W, Epplen JT. Source: Human Mutation. 2000 January; 15(1): 122. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10612851

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Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia. Author(s): Manning BM, Quane KA, Lynch PJ, Urwyler A, Tegazzin V, Krivosic-Horber R, Censier K, Comi G, Adnet P, Wolz W, Lunardi J, Muller CR, McCarthy TV. Source: Human Mutation. 1998; 11(1): 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9450902

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Novel mutations in C-terminal channel region of the ryanodine receptor in malignant hyperthermia patients. Author(s): Oyamada H, Oguchi K, Saitoh N, Yamazawa T, Hirose K, Kawana Y, Wakatsuki K, Oguchi K, Tagami M, Hanaoka K, Endo M, Iino M. Source: Japanese Journal of Pharmacology. 2002 February; 88(2): 159-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11928716

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Novel skeletal muscle ryanodine receptor mutation in a large Brazilian family with malignant hyperthermia. Author(s): McWilliams S, Nelson T, Sudo RT, Zapata-Sudo G, Batti M, Sambuughin N. Source: Clinical Genetics. 2002 July; 62(1): 80-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12123492

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Obstetric anesthesia for a patient with malignant hyperthermia susceptibility. Author(s): Wadhwa RK. Source: Anesthesiology. 1977 January; 46(1): 63-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=831594

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On the nature of the link between malignant hyperthermia and exertional heatstroke. Author(s): Bourdon L, Canini F. Source: Medical Hypotheses. 1995 September; 45(3): 268-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8569550

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Optimal treatment for malignant hyperthermia today. Author(s): Krivosic-Horber R. Source: Acta Anaesthesiol Belg. 1988; 39(3 Suppl 2): 255-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3176862

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OR crisis. Malignant hyperthermia. Author(s): Mavity CB. Source: Todays or Nurse. 1985 January; 7(1): 8-11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3844879

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Orally administered dantrolene for prophylaxis of malignant hyperthermia. Author(s): Pandit SK, Kothary SP, Cohen PJ. Source: Anesthesiology. 1979 February; 50(2): 156-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=434489

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Osteogenesis imperfecta and malignant hyperthermia. Is there a relationship? Author(s): Porsborg P, Astrup G, Bendixen D, Lund AM, Ording H. Source: Anaesthesia. 1996 September; 51(9): 863-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8882252

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Outpatient dental treatment of pediatric patients with malignant hyperthermia: report of three cases. Author(s): Steelman R, Holmes D. Source: Asdc J Dent Child. 1992 January-February; 59(1): 62-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1537944

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Overheating alone can trigger malignant hyperthermia in piglets. Author(s): Denborough M, Hopkinson KC, O'Brien RO, Foster PS. Source: Anaesthesia and Intensive Care. 1996 June; 24(3): 348-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8805890

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Pathological findings in 165 patients explored for malignant hyperthermia susceptibility. Author(s): Figarella-Branger D, Kozak-Ribbens G, Rodet L, Aubert M, Borsarelli J, Cozzone PJ, Pellissier JF. Source: Neuromuscular Disorders : Nmd. 1993 September-November; 3(5-6): 553-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8186710

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Pathophysiological role of the serotonin system in malignant hyperthermia. Author(s): Wappler F, Fiege M, Schulte am Esch J. Source: British Journal of Anaesthesia. 2001 November; 87(5): 794-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11878537

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Patients who are susceptible to malignant hyperthermia. Author(s): Bowie JR. Source: Nurse Anesth. 1993 June; 4(2): 99. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8347698

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Patients with malignant hyperthermia demonstrate an altered calcium control mechanism in B lymphocytes. Author(s): Sei Y, Brandom BW, Bina S, Hosoi E, Gallagher KL, Wyre HW, Pudimat PA, Holman SJ, Venzon DJ, Daly JW, Muldoon S. Source: Anesthesiology. 2002 November; 97(5): 1052-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12411786

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Perioperative severe rhabdomyolysis revealing susceptibility to malignant hyperthermia. Author(s): Fierobe L, Nivoche Y, Mantz J, Elalaoui Y, Veber B, Desmonts JM. Source: Anesthesiology. 1998 January; 88(1): 263-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9447880

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Phenotyping malignant hyperthermia susceptibility by measuring halothane-induced changes in myoplasmic calcium concentration in cultured human skeletal muscle cells. Author(s): Girard T, Treves S, Censier K, Mueller CR, Zorzato F, Urwyler A. Source: British Journal of Anaesthesia. 2002 October; 89(4): 571-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393358

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Positive malignant hyperthermia susceptibility in vitro test in a patient with mitochondrial myopathy and myoadenylate deaminase deficiency. Author(s): Fricker RM, Raffelsberger T, Rauch-Shorny S, Finsterer J, Muller-Reible C, Gilly H, Bittner RE. Source: Anesthesiology. 2002 December; 97(6): 1635-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459698

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Postanaesthetic myoglobinuric renal failure: an isolated expression of malignant hyperthermia. Author(s): Acquarone N, Garibotto G, Tegazzin V, Sofia A, Gurreri G. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1994; 9(5): 567-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8090342

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Postexercise muscle cramping associated with positive malignant hyperthermia contracture testing. Author(s): Ogletree JW, Antognini JF, Gronert GA. Source: The American Journal of Sports Medicine. 1996 January-February; 24(1): 49-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8638753

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Postoperative variant of malignant hyperthermia: report of a case. Author(s): Chuong R. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1992 November; 50(11): 1235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1403283

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Practical points in the management of malignant hyperthermia. Author(s): Saleh KL. Source: J Post Anesth Nurs. 1992 October; 7(5): 327-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1403962

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Predicting malignant hyperthermia susceptibility. Author(s): Allen G. Source: Anesthesiology. 1998 September; 89(3): 797-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9743426

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Prediction of accelerated Ca-induced Ca release rate by clinical findings in malignant hyperthermia susceptible subjects. Author(s): Kawamoto M, Mukaida K, Maehara Y, Yuge O. Source: In Vivo. 2001 January-February; 15(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11286128

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Preparation of the Siemens KION anesthetic machine for patients susceptible to malignant hyperthermia. Author(s): Petroz GC, Lerman J. Source: Anesthesiology. 2002 April; 96(4): 941-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964603

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Preparing a new generation anaesthetic machine for patients susceptible to malignant hyperthermia. Author(s): Schonell LH, Sims C, Bulsara M. Source: Anaesthesia and Intensive Care. 2003 February; 31(1): 58-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635397

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Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility. Author(s): Monnier N, Krivosic-Horber R, Payen JF, Kozak-Ribbens G, Nivoche Y, Adnet P, Reyford H, Lunardi J. Source: Anesthesiology. 2002 November; 97(5): 1067-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12411788

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Prolonged malignant hyperthermia in the absence of triggering agents. Author(s): Pollock N, Hodges M, Sendall J. Source: Anaesthesia and Intensive Care. 1992 November; 20(4): 520-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1463189

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Propofol and malignant hyperthermia susceptibility. Author(s): Pollock AN, McKenzie AJ, Hodges M, Snoeck MM. Source: Anaesthesia and Intensive Care. 1997 October; 25(5): 583-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9352778

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Propofol and malignant hyperthermia: a case for day-case anaesthesia? Author(s): Khan KJ, Cooper GM. Source: Anaesthesia. 1993 May; 48(5): 455-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8317682

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Propofol use in malignant hyperthermia: a case report. Author(s): Freedman G, Sampson IH, Cagen S. Source: The Mount Sinai Journal of Medicine, New York. 1993 September; 60(4): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8232382

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Rapid intervention for an episode of malignant hyperthermia. Author(s): Chartrand D. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 February; 50(2): 104-7. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560297

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Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing? Author(s): Robinson RL, Anetseder MJ, Brancadoro V, van Broekhoven C, Carsana A, Censier K, Fortunato G, Girard T, Heytens L, Hopkins PM, Jurkat-Rott K, Klinger W, Kozak-Ribbens G, Krivosic R, Monnier N, Nivoche Y, Olthoff D, Rueffert H, Sorrentino V, Tegazzin V, Mueller CR. Source: European Journal of Human Genetics : Ejhg. 2003 April; 11(4): 342-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700608

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Reduced inhibitory effect of Mg2+ on ryanodine receptor-Ca2+ release channels in malignant hyperthermia. Author(s): Laver DR, Owen VJ, Junankar PR, Taske NL, Dulhunty AF, Lamb GD. Source: Biophysical Journal. 1997 October; 73(4): 1913-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9336187

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Regional lactate and carbon dioxide concentrations in a metabolic test for malignant hyperthermia. Author(s): Anetseder M, Hager M, Muller-Reible C, Roewer N. Source: Lancet. 2003 August 9; 362(9382): 494; Discussion 494-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927444

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Reproducibility of in vitro contracture test results in patients tested for malignant hyperthermia susceptibility. Author(s): Islander G, Ording H, Bendixen D, Ranklev Twetman E. Source: Acta Anaesthesiologica Scandinavica. 2002 October; 46(9): 1144-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12366511

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Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations. Author(s): Fiege M, Wappler F, Weisshorn R, Ulrich Gerbershagen M, Steinfath M, Schulte Am Esch J. Source: Anesthesiology. 2002 August; 97(2): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151923

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Results of in vitro contracture tests for the diagnosis of malignant hyperthermia susceptibility in monozygote twins. Author(s): Islander G, Ranklev Twetman E. Source: Acta Anaesthesiologica Scandinavica. 1997 June; 41(6): 731-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9241333

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Rhabdomyolysis after infection and taking a cold medicine in a patient who was susceptible to malignant hyperthermia. Author(s): Kasamatsu Y, Osada M, Ashida K, Azukari K, Yoshioka K, Ohsawa A. Source: Intern Med. 1998 February; 37(2): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9550599

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Rhabdomyolysis and myalgia associated with anticholesterolemic treatment as potential signs of malignant hyperthermia susceptibility. Author(s): Guis S, Bendahan D, Kozak-Ribbens G, Figarella-Branger D, Mattei JP, Pellissier JF, Treffouret S, Bernard V, Lando A, Cozzone PJ. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 237-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687516

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Rhabdomyolysis following severe physical exercise in a patient with predisposition to malignant hyperthermia. Author(s): Kochling A, Wappler F, Winkler G, Schulte am Esch JS. Source: Anaesthesia and Intensive Care. 1998 June; 26(3): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9619231

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Ryanodine receptor gene (RYR1) mutations for diagnosing susceptibility to malignant hyperthermia. Author(s): Urwyler A, Halsall PJ, Mueller C, Robinson R. Source: Acta Anaesthesiologica Scandinavica. 2003 April; 47(4): 492; Author Reply 493. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694155

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RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. Author(s): Robinson RL, Brooks C, Brown SL, Ellis FR, Halsall PJ, Quinnell RJ, Shaw MA, Hopkins PM. Source: Human Mutation. 2002 August; 20(2): 88-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12124989

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Scanning for mutations of the ryanodine receptor (RYR1) gene by denaturing HPLC: detection of three novel malignant hyperthermia alleles. Author(s): Tammaro A, Bracco A, Cozzolino S, Esposito M, Di Martino A, Savoia G, Zeuli L, Piluso G, Aurino S, Nigro V. Source: Clinical Chemistry. 2003 May; 49(5): 761-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709367

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Serotonin toxicity and malignant hyperthermia: role of 5-HT2 receptors. Author(s): Isbister GK, Whyte IM. Source: British Journal of Anaesthesia. 2002 April; 88(4): 603; Author Reply 603-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12066745

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Several interacting genes influence the malignant hyperthermia phenotype. Author(s): Robinson R, Hopkins P, Carsana A, Gilly H, Halsall J, Heytens L, Islander G, Jurkat-Rott K, Muller C, Shaw MA. Source: Human Genetics. 2003 February; 112(2): 217-8. Epub 2002 November 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522565

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Severe rhabdomyolysis due to malignant hyperthermia during renal transplantation procedure can cause delayed graft function. Author(s): Caglar K, Orhan ME, Gulec B, Yavuz I, Yenicesu M, Guzeldemir E, Vural A. Source: American Journal of Nephrology. 2002 January-February; 22(1): 81-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11919407

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Similar susceptibility to halothane, caffeine and ryanodine in vitro reflects pharmacogenetic variability of malignant hyperthermia. Author(s): Ginz HF, Girard T, Censier K, Urwyler A. Source: European Journal of Anaesthesiology. 2004 February; 21(2): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977348

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Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype. Author(s): Sambuughin N, McWilliams S, de Bantel A, Sivakumar K, Nelson TE. Source: American Journal of Human Genetics. 2001 July; 69(1): 204-8. Epub 2001 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11389482

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Spontaneous occurrence of the disposition to malignant hyperthermia. Author(s): Rueffert H, Olthoff D, Deutrich C. Source: Anesthesiology. 2004 March; 100(3): 731-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15108991

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Suspected malignant hyperthermia during isoflurane anesthesia--a case report. Author(s): Liao YC, Wang JJ, Chien CC, Li MJ, Liu YH, Chang CF. Source: Acta Anaesthesiol Sin. 1998 March; 36(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9807851

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Suspected malignant hyperthermia reactions in New Zealand. Author(s): Pollock AN, Langton EE, Couchman K, Stowell KM, Waddington M. Source: Anaesthesia and Intensive Care. 2002 August; 30(4): 453-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180584

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Suxamethonium, masseter spasm and later malignant hyperthermia. Author(s): Ramirez JA, Cheetham ED, Laurence AS, Hopkins PM. Source: Anaesthesia. 1998 November; 53(11): 1111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10023282

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Testing for malignant hyperthermia. Author(s): Rosenberg H, Antognini JF, Muldoon S. Source: Anesthesiology. 2002 January; 96(1): 232-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753023

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The differential effect of halothane and 1,2-dichlorohexafluorocyclobutane on in vitro muscle contractures of patients susceptible to malignant hyperthermia. Author(s): Kindler CH, Girard T, Gong D, Urwyler A. Source: Anesthesia and Analgesia. 2002 April; 94(4): 1028-33, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916818

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The G1021A substitution in the RYR1 gene does not cosegregate with malignant hyperthermia susceptibility in a British pedigree. Author(s): Adeokun AM, West SP, Ellis FR, Halsall PJ, Hopkins PM, Foroughmand AM, Iles DE, Robinson RL, Stewart AD, Curran JL. Source: American Journal of Human Genetics. 1997 April; 60(4): 833-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9106529

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The Israeli Diagnostic Center for Malignant Hyperthermia: 7-years' accumulated experience. Author(s): Glauber V, Ben Abraham R, Zweig A, Perel A. Source: Isr J Med Sci. 1997 October; 33(10): 643-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9397136

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The role of the skeletal muscle ryanodine receptor (RYR1) gene in malignant hyperthermia and central core disease. Author(s): MacLennan DH, Phillips MS. Source: Soc Gen Physiol Ser. 1995; 50: 89-100. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7676327

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The ryanodine contracture test may help diagnose susceptibility to malignant hyperthermia. Author(s): Reuter DA, Anetseder M, Muller R, Roewer N, Hartung EJ. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 AugustSeptember; 50(7): 643-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944436

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The sensitivity and specificity of the caffeine-halothane contracture test: a report from the North American Malignant Hyperthermia Registry. The North American Malignant Hyperthermia Registry of MHAUS. Author(s): Allen GC, Larach MG, Kunselman AR. Source: Anesthesiology. 1998 March; 88(3): 579-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9523799

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The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia. Author(s): Phillips MS, Khanna VK, De Leon S, Frodis W, Britt BA, MacLennan DH. Source: Human Molecular Genetics. 1994 December; 3(12): 2181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7881417

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This looks like malignant hyperthermia! Author(s): Rivera PH, Worley C. Source: J Post Anesth Nurs. 1995 October; 10(5): 265-73; Quiz 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8632363

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Tranylcypromine intoxication with malignant hyperthermia, delirium, and thrombocytopenia. Author(s): Pennings EJ, Verkes RJ, de Koning J, Bommele JJ, Jansen GS, Vermeij P. Source: Journal of Clinical Psychopharmacology. 1997 October; 17(5): 430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9316000

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Ultrasonography: not useful in detecting susceptibility to malignant hyperthermia. Author(s): Antognini JF, Anderson M, Cronan M, McGahan JP, Gronert GA. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1994 May; 13(5): 371-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8015044

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Unexplained increases in serum creatine kinase levels: its relation to malignant hyperthermia susceptibility. Author(s): Lingaraju N, Rosenberg H. Source: Anesthesia and Analgesia. 1991 May; 72(5): 702-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2018229

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Update for nurse anesthetists. Part 6. Full-body patient simulation technology: gaining experience using a malignant hyperthermia model. Author(s): Hotchkiss MA, Mendoza SN. Source: Aana Journal. 2001 February; 69(1): 59-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11759141

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Upper limb compartment syndromes: a complication of malignant hyperthermia in a patient with ill-defined myopathy. Author(s): O'Donnell CJ, Beck DH, Taylor BL, Smith GB. Source: British Journal of Anaesthesia. 1995 March; 74(3): 343-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7718387

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Uptake and release of calcium ions by heavy sarcoplasmic reticulum fraction of normal and malignant hyperthermia-susceptible human skeletal muscle. Author(s): McSweeney DM, Heffron JJ. Source: Int J Biochem. 1990; 22(4): 329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2140103

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Use of atracurium in a patient susceptible to malignant hyperthermia. Author(s): Michel PA, Fronefield HP. Source: Anesthesiology. 1985 February; 62(2): 213. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3838224

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Use of local anesthetics in malignant hyperthermia. Author(s): Brownell AK, Paasuke RT. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1986 May 1; 134(9): 993-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3697883

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Use of the calcium agonist BAY K 8644 for in vitro diagnosis of susceptibility to malignant hyperthermia. Author(s): Adnet PJ, Krivosic-Horber RM, Haudecoeur G, Adamantidis MM, Reyford GH, Imbenotte M, Cordonnier C. Source: British Journal of Anaesthesia. 1990 December; 65(6): 791-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1702303

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Use of tricyclic antidepressants in a patient with malignant hyperthermia. Author(s): Richter MA, Joffe RT. Source: The American Journal of Psychiatry. 1987 April; 144(4): 526. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3565631

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Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia. Author(s): Ording H, Fonsmark L. Source: British Journal of Anaesthesia. 1988 March; 60(4): 445-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2895665

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Value of mass spectrometry in early diagnosis of malignant hyperthermia. Author(s): Dunn CM, Maltry DE, Eggers GW Jr. Source: Anesthesiology. 1985 September; 63(3): 333. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3927786

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Variants of malignant hyperthermia. Special problems for the paediatric anaesthesiologist. Author(s): Rosenberg H, Shutack JG. Source: Paediatric Anaesthesia. 1996; 6(2): 87-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846290

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Verapamil and malignant hyperthermia--case reports. Author(s): Keilani MR, Al-Shanableh JS. Source: Middle East J Anesthesiol. 1985 February; 8(1): 37-45. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4010529

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Vitamin E and malignant hyperthermia. Author(s): James P. Source: British Medical Journal. 1979 January 20; 1(6157): 200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=421028

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Vitamin E and malignant hyperthermia. Author(s): James P. Source: British Medical Journal. 1978 May 20; 1(6123): 1345. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=647267

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Voltage-dependent calcium release in human malignant hyperthermia muscle fibers. Author(s): Struk A, Lehmann-Horn F, Melzer W. Source: Biophysical Journal. 1998 November; 75(5): 2402-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9788935

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When seconds count: treating malignant hyperthermia. Author(s): French MM, Phillips KF. Source: Rn. 1984 November; 47(11): 26-31, 74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6208597

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Would morphine in large doses prevent malignant hyperthermia? Author(s): Brandt MR, Kehlet H, Jorgensen PF, Smith M. Source: Anesthesiology. 1978 July; 49(1): 57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=666049

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CHAPTER 2. NUTRITION AND MALIGNANT HYPERTHERMIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and malignant hyperthermia.

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

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

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

5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients. Author(s): Department of Anaesthesiology, University Hospital Eppendorf, Hamburg, Germany. [email protected] Source: Wappler, F Scholz, J Fiege, M Richter, A Steinfath, M Weisshorn, R Schulte am Esch, J Naunyn-Schmiedebergs-Arch-Pharmacol. 1999 October; 360(4): 376-81 0028-1298

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An association between certain congenital abnormalities and the malignant hyperthermia trait. Author(s): Department of Physiology, University of the Witwatersrand, Johannesburg. Source: Gericke, G S Isaacs, H S-Afr-Med-J. 1990 June 2; 77(11): 570-4 0038-2469

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Caffeine sensitivity of sarcoplasmic reticulum of fast and slow fibers from normal and malignant hyperthermia human muscle. Author(s): National Research Council Unit for Muscle Biology and Physiopathology, University of Padova, Italy. Source: Salviati, G Betto, R Ceoldo, S Tegazzin, V Della Puppa, A Muscle-Nerve. 1989 May; 12(5): 365-70 0148-639X

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Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle. Author(s): Department of Basic and Clinical Pharmacology, Universidade Federal do Rio de Janeiro, Brazil. Source: Sudo, R T Nelson, T E J-Pharmacol-Exp-Ther. 1997 September; 282(3): 1331-6 0022-3565

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Contractures in skeletal muscle of malignant hyperthermia susceptible patients after in vitro exposure to sevoflurane. Author(s): Department of Anaesthesiology, University Hospital Nijmegen, The Netherlands. [email protected] Source: Snoeck, M M Gielen, M J Tangerman, A van Egmond, J Dirksen, R ActaAnaesthesiol-Scand. 2000 March; 44(3): 334-7 0001-5172

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Current views of the molecular basis of the malignant hyperthermia syndrome. Author(s): Department of Biochemistry, University College Cork, Ireland. Source: Heffron, J J McCarthy, T V Acta-Anaesthesiol-Belg. 1990; 41(2): 73-8 0001-5164

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Fura-2 detected myoplasmic calcium and its correlation with contracture force in skeletal muscle from normal and malignant hyperthermia susceptible pigs. Author(s): Neuroiogische Klinik, Technischen Universitat Munchen, Federal Republic of Germany. Source: Iaizzo, P A Klein, W Lehmann Horn, F Pflugers-Arch. 1988 June; 411(6): 648-53 0031-6768

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Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels. Author(s): Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada. Source: Tong, J McCarthy, T V MacLennan, D H J-Biol-Chem. 1999 January 8; 274(2): 693-702 0021-9258

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Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations. Author(s): Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany. [email protected] Source: Rueffert, H Olthoff, D Deutrich, C Meinecke, C D Froster, U G ActaAnaesthesiol-Scand. 2002 July; 46(6): 692-8 0001-5172

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Mutations to Gly2370, Gly2373 or Gly2375 in malignant hyperthermia domain 2 decrease caffeine and cresol sensitivity of the rabbit skeletal-muscle Ca2+-release channel (ryanodine receptor isoform 1). Author(s): Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, Ontario M5G 1L6, Canada. Source: Du, G G Oyamada, H Khanna, V K MacLennan, D H Biochem-J. 2001 November 15; 360(Pt 1): 97-105 0264-6021

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Prolonging viability of swine muscle biopsy specimens in malignant hyperthermia testing. Author(s): Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. [email protected] Source: Bina, S Karan, S M Lojeski, E W Mongan, P D Muldoon, S M Anesth-Analg. 2001 September; 93(3): 781-6 0003-2999

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Propofol anaesthesia in malignant hyperpyrexia susceptible swine. Author(s): Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT. Source: Foster, P S Hopkinson, K C Denborough, M A Clin-Exp-Pharmacol-Physiol. 1992 March; 19(3): 183-6 0305-1870

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Propofol is a 'safe' anaesthetic agent in malignant hyperthermia susceptible patients. Author(s): Department of Anaesthesia and Intensive Care, Palmerston North Hospital, New Zealand. Source: McKenzie, A J Couchman, K G Pollock, N Anaesth-Intensive-Care. 1992 May; 20(2): 165-8 0310-057X

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The effect of cyclopiazonic acid on the development of pale, soft, and exudative pork from pigs of defined malignant hyperthermia genotype. Author(s): Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824, USA. Source: Byrem, T M Booren, A M Hill, G M Chu, F S Strasburg, G M J-Anim-Sci. 1999 January; 77(1): 166-72 0021-8812

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The importance of calcium ions for in vitro malignant hyperthermia testing. Author(s): Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192. Source: Fletcher, J E Huggins, F J Rosenberg, H Can-J-Anaesth. 1990 September; 37(6): 695-8 0832-610X

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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND MALIGNANT HYPERTHERMIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to malignant hyperthermia. 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 malignant hyperthermia 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 “malignant hyperthermia” (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 malignant hyperthermia: •

Clinical pharmacology of neuromuscular blocking agents. Author(s): Fisher DM. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 June 1; 56(11 Suppl 1): S4-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10437710

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Creatine monohydrate supplementation and the quality of fresh pork in normal and halothane carrier pigs. Author(s): Maddock RJ, Bidner BS, Carr SN, McKeith FK, Berg EP, Savell JW. Source: Journal of Animal Science. 2002 April; 80(4): 997-1004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12002337

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Effects of a high n-3 fatty acid diet on membrane lipid composition of heart and skeletal muscle in normal swine and in swine with the genetic mutation for malignant hyperthermia. Author(s): Otten W, Iaizzo PA, Eichinger HM. Source: Journal of Lipid Research. 1997 October; 38(10): 2023-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9374125

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Malignant hyperthermia induced by curare. Author(s): Britt BA, Webb GE, LeDuc C. Source: Can Anaesth Soc J. 1974 July; 21(4): 371-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4836914

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Malignant hyperthermia triggered coincidentally after reversal of neuromuscular blockade in a patient from the Hmong people of Laos. Author(s): Wohlfeil ER, Woehlck HJ, McElroy ND. Source: Anesthesiology. 1998 June; 88(6): 1667-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9637662

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Malignant hyperthermia. Author(s): Lee TL, Kumar A, Ng KS, Foo KL. Source: Ann Acad Med Singapore. 1990 May; 19(3): 416-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2393248

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Malignant hyperthermia-like reaction secondary to ingestion of hops in five dogs. Author(s): Duncan KL, Hare WR, Buck WB. Source: J Am Vet Med Assoc. 1997 January 1; 210(1): 51-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8977648

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Porcine malignant hyperthemia IV: Neuromuscular blockade. Author(s): Hall GM, Lucke JN, Lister D. Source: British Journal of Anaesthesia. 1976 December; 48(12): 1135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1023949

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Procaine in malignant hyperpyrexia. Author(s): Moulds RF, Denborough MA. Source: British Medical Journal. 1972 December 2; 4(839): 526-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4642792

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Prospects for hyperthermia in human cancer therapy.Part I: hyperthermic effects in man and spontaneous animal tumors. Author(s): Miller RC, Connor WG, Heusinkveld RS, Boone ML.

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Source: Radiology. 1977 May; 123(2): 489-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=322207 •

Sevoflurane stimulates inositol 1,4,5-trisphosphate in skeletal muscle. Author(s): Kudoh A, Matsuki A. Source: Anesthesia and Analgesia. 2000 August; 91(2): 440-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10910865

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TENS-induced pain control in a malignant hyperthermia-susceptible patient. Author(s): Stenberg W. Source: Anesthesia Progress. 1994; 41(4): 100-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8934960

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The antioxidant abnormality in the stress-susceptible pig. Effect of vitamin E supplementation. Author(s): Duthie GG, Arthur JR. Source: Annals of the New York Academy of Sciences. 1989; 570: 322-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2629602

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Vitamin-mineral supplementation and accelerated chilling effects on quality of pork from pigs that are monomutant or noncarriers of the halothane gene. Author(s): Kerth CR, Carr MA, Ramsey CB, Brooks JC, Johnson RC, Cannon JE, Miller MF. Source: Journal of Animal Science. 2001 September; 79(9): 2346-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583421

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Herbs and Supplements Hops Source: Prima Communications, Inc.www.personalhealthzone.com

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

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CHAPTER 4. PATENTS ON MALIGNANT HYPERTHERMIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “malignant hyperthermia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on malignant hyperthermia, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Malignant Hyperthermia By performing a patent search focusing on malignant hyperthermia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted

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

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

Diagnosing malignant hyperthermia susceptibility by detection of abnormal proteolytic enzyme digestion fragments of the ryanodine receptor Inventor(s): Campbell; Kevin P. (Iowa City, IA), Kahl; Steven D. (Iowa City, IA), Knudson; C. Michael (Iowa City, IA), Louis; Charles F. (St. Paul, MN), Mickelson; James R. (St. Paul, MN) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN), University of Iowa Research Foundation (Iowa, IA) Patent Number: 5,242,801 Date filed: August 6, 1990 Abstract: The present invention relates to a method of diagnosing malignant hyperthermia susceptibility by detecting abnormal ryanodine receptor fragments following proteolytic enzyme digestion of ryanodine receptors isolated from the sarcoplasmic reticulum of mammalian skeletal muscle. The detection of abnormal ryanodine receptor fragments is indicative of malignant hyperthermia susceptibility. Excerpt(s): Malignant hyperthermia is an inherited skeletal muscle disorder of humans and pigs. The disease is characterized by an accelerated muscle metabolism, contracture development, and rapidly rising temperature in response to certain halogenated anesthetics. Once initiated, a vicious cycle is established and a fulminant syndrome evolves in which the body temperature may exceed 109.degree. F. The clinical picture is generally accompanied by muscle rigidity, tachychardia and other signs of circulatory and metabolic stress. The syndrome may progress directly to rigor and death from cardiovascular stress unless the malignant hyperthermia episode is recognized and treated promptly with the skeletal muscle relaxant, dantrolene. The reported incidence of malignant hyperthermia ranges from approximately 1 per 10,000 to 1 per 50,000 anesthetics, with an apparently higher incidence in children. In addition to triggering malignant hyperthermia by halothane anesthetic, porcine malignant hyperthermia is also consistently triggered by excitement, apprehension, exercise, or environmental stress such as heat or hypoxia. Episodes of malignant hyperthermia in pigs yield inferior, pale, soft and exudative pork. Active malignant hyperthermia results in a dramatic elevation of intracellular calcium in skeletal muscle fibers. The exact cause of the explosive rise in sarcoplasmic calcium is not completely understood. Several laboratories, however, have found that calcium release from malignant hyperthermia susceptible sarcoplasmic reticulum in skeletal muscle differs from that of normal sarcoplasmic reticulum in both isolated vesicles, as well as intact and skinned fibers. Consequently, the calcium release channel of the sarcoplasmic reticulum has been suspected of playing a significant role in malignant hyperthermia. Web site: http://www.delphion.com/details?pn=US05242801__

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Diagnosis for malignant hyperthermia Inventor(s): Britt; Beverley A. (Etobicoke, CA), MacLennan; David H. (Toronto, CA), Worton; Ronald G. (Toronto, CA) Assignee(s): HSC Research and Development Limited Partnership (Toronto, CA), The Toronto Hospital (Toronto, CA), The University of Toronto Innovations Foundation (Toronto, CA) Patent Number: 5,413,907 Date filed: April 13, 1992 Abstract: A method for isolating a cDNA specific for the human ryanodine receptor is disclosed. The gene is associated with malignant hyperthermia, a hypermetabolic syndrome triggered primarily by inhalation anesthetics. The cDNA can be cloned and expressed in a recombinant plasmid or phage. The cDNA, or fragments thereof, is used as diagnostic probes for individuals at risk for malignant hyperthermia using restriction fragment length polymorphism analysis. The cDNA is that sequenced in FIG. 2 of this specification. Excerpt(s): This invention relates to the animal disease malignant hyperthermia (MH) and to the cloning and characterization of a gene associated with (MH), and to the development of methods for detecting individuals susceptible to MH. Although malignant hyperthermia is associated primarily with humans and was first realized as a reaction to inhalation anaesthetics, it is understood that MH is also a very common problem in certain animals, particularly pigs. There is therefore particular commercial interest in developing suitable assays to determine MH in pigs, as well as providing suitable diagnosis to test humans to avoid life threatening circumstances in the operating room. Malignant hyperthermia (MH) is an inherited predisposition to a hypermetabolic syndrome (adverse reaction) triggered by inhalation anaesthetics such as halothane and some skeletal muscle relaxants such as succinylcholine. The primary defect in MH is related to a sustained increase in myoplasmic calcium which causes muscle contracture and increased glycolysis concomitant with the production of H.sub.2 O, CO.sub.2 and heat and excessive consumption of O.sub.2. Other signs of the disorder (including the hyperthermia for which it was named) may be explained as a direct result of muscle contracture and increased glycolysis [Steward, D. J. and O'Connor, G. A. R, "Malignant Hyperthermia--The Acute Crisis", in Britt B. A. ed. Malignant Hyperthermia, Boston, Martinus Nijhoff, (1987)]. Web site: http://www.delphion.com/details?pn=US05413907__

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Diagnosis for porcine malignant hyperthermia Inventor(s): MacLennan; David H. (Toronto, CA), O'Brien; Peter J. (Guelph, CA) Assignee(s): The University of Toronto Innovations Foundation (Ontario, CA), University of Guelph (Ontario, CA) Patent Number: 5,358,649 Date filed: March 15, 1993 Abstract: A purified DNA molecule comprises a DNA sequence of approximately 15.1 kb coding for normal or mutant RYR1 protein having a molecular weight of approximately 564,740 daltons. The DNA molecule has an endonuclease restriction map of FIG. 1 and a sequence of FIG. 2.

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Excerpt(s): This invention relates to the animal disease malignant hyperthermia (MH), to the cloning and characterization of a gene associated with MH in swine, and to the development of DNA and antibody-based methods for detecting individual pigs susceptible to MH. Malignant hyperthermia (MH) is a hypermetabolic myopathy which is triggered in genetically-susceptible human and animal individuals by potent, volatile anesthetics such as halothane [Denborough and Lovell (1960) Lancet 2, 545: Harrison et al. (1968) Brit. Med. J. 3:594-595] or by depolarizing muscle relaxants such as succinycholine [Harrison et al. (1969) Brit. J. Anaesthesia 41:844-855]. In swine, it is also referred to as porcine stress syndrome [Topel (1968) Mod. Vet. Pract. 49:40-41; 59-60] because it may be triggered by exertional [Ludvigsen (1953) Internat. Vet. Congr. Stockholm 1:602-606] thermal [Forrest et al. (1968) J. of Appl. Physiol. 24:33-39], anoxic [Lister et al. (1970) Am. J. Physiol. 218:102-107], or mechanical [Gronert (1980) Anaesthesiol. 44:36-43] stressors as well as anesthesia [Hall et al (1966) Brit. Med. J. 4:1305]. A similar stress syndrome may occur in MH-susceptible (MHS) humans [Wingard (1974) Lancet 2;1450-1451] and dogs [O'Brien et al. (1983) Can. Vet. J. 24:172177]. MH is characterized by the peracute development of contracture and maximal rate of metabolism in muscle. These have been proposed to occur due to an uncontrollable and sustained elevation of myoplasmic calcium [Britt and Kalow (1970) Can. Anesthetists Soc. J. 17:316-330: Lopez et al. (1985) Biophys. J. 47:313a], which is known to activate the contractile apparatus and metabolic machinery of skeletal muscle [Martonosi (1984) Physiol. Rev. 64:1240-1319). The hyperactivity of muscle which occurs during MH results in the depletion of ATP and glycogen stores and the excessive formation of carbon dioxide, lactic acid and heat. This thermogenesis, in conjunction with peripheral vasoconstriction, leads to hyperthermia. The rapid rate of aerobic metabolism, by depleting blood oxygen, causes cyanosis [Gronert (1980) Anaesthesiol. 53:395-423]. During MH, glycogenolysis, rhabdomyolysis and acidemia cause the release of large amounts of potassium from muscle and liver [Hall et al. (1980) Brit. J. Anaesthesiol. 52:11-17 ] into the vascular compartment. The resultant hyperkalemia contributes to the development of cardiac dysrhythmia and subsequent heart failure [Britt (1983) in "Complications in Anesthesiology" F. K. Orkin and L. H. Cooperman (eds) Lippincott, pp. 290-313]. Web site: http://www.delphion.com/details?pn=US05358649__ •

Malignant hyperthermia mattress Inventor(s): Duncan; Lawrence W. (Munster Hamlet, CA), Samson; J. E. Benoit (Nepean, CA), Steffler; Jean C. (Downsview, CA) Assignee(s): Her Majesty the Queen in right of Canada, as represented by the Minister (Ottawa, CA) Patent Number: 4,442,838 Date filed: March 25, 1982 Abstract: A mattress for the treatment of malignant hyperthermia comprises a base to overlie an operating table and an inflatable wall extending around the periphery of the base. The wall includes a pair of discontinuities which permit the patient's arms to extend across the inflated wall. A sealing cuff and flap encompass the arm and seal the discontinuity to prevent egress of water from around the patient. A recess is provided in the wall adjacent the patient's head to allow the anethetist access to the patient when the wall is inflated.

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Excerpt(s): The present invention relates to a mattress for use in conjunction with a surgical operating table and more particularly to such a mattress that may be used during the treatment of malignant hyperthermia. Malignant hyperthermia is a lifethreatening clinical condition steming from a complication during the administration of an anesthetic under surgical operating conditions. A reaction between the anesthetic agent and the patient's tissues causes a rapid rise in body temperature, which if not reduced promptly, could cause death. This condition is treated by covering the patient with crushed ice to promote rapid cooling. At the same time it is necessary to maintain the life support systems, such as the administration of anesthetic and plasma, whilst continuing surgical operation on the patient so that he may recover consciousness as quickly as possible. Web site: http://www.delphion.com/details?pn=US04442838__ •

Process and kit for determining blood platelet stress Inventor(s): Solomons; Clive C. (164 S. Fairfax, Denver, CO 80222) Assignee(s): none reported Patent Number: 4,600,696 Date filed: June 22, 1984 Abstract: A process and kit are provided for measuring chemical and physical stresses on the blood platelets of a human patient by measuring reduction in ATP (adenosine triphosphate) and ADP (adenosine diphosphate) concentrations while measuring increases in the ATP degradation products HYPX (hypoxanthine) and AMP (adenosine monophosphate). The process is useful for measuring a human patient's risk to internal stress such as reduction in the size of blood vessels, to response to various environmental changes as well as to a variety of treatments including drug treatment, risk of malignant hyperthermia in response to anesthetic administration or in response to vascular or organ transplant. Excerpt(s): This invention relates to a process for accurately measuring chemical and physical stresses on blood platelets of a human patient and for relating the measured stress to the effect of an outside agent to which the patient is exposed. More particulatly, the present invention relates to such a process and to a kit adapted to effect the stress measurement. There are approximately 300,000 platelets per cubic mm. blood circulating in the blood stream. Platelets are derived from bone marrow cells and their most dramatic function is to prevent blood loss by forming a plug together with other blood products which stops the flow of blood from an injured vessel. Platelets are induced to aggregate to each other and to adhere to a cut or any foreign surface by metabolites such as ADP, thrombin and epinephrine, as well as by exposed collagen or atherosclerotic plaque in the walls of blood vessels. Changes induced by these agents cause platelets to release substances such as ADP into their immediate surroundings, thus affecting neaby platelets to follow suit. In this way a minor lesion in a blood vessel can accumulate platelets and other debris eventually blocking the flow of blood. If the vessel is a coronary artery, the individual experiences a "heart attack". If the vessel is in the brain, a "stroke" results. Very often there is little warning of the impending catastrophy until the vessel is 80-90% occluded and alarming clinical symptoms suddenly become noticeable. Nevertheless, circulating platelets continually pass close to forming clots every two minutes and accumulate information indicative of progressive pathology before any symptoms are felt. Thus, the measurement of early stress reflected in platelets can lead to the institution of highly cost-effective preventative medical

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therapy to reduce the morbidity and mortality of thrombotic disease. Communicating with stressed platelets before they become irreversibly attached to a clot requires the creative use of technology to decode the internal cell language so that relatively undistorted messages can be registered and correlated with progression of the disease and the effectiveness of treatment. The platelet like all other living cells uses ATP (adenosine triphosphate) as the most effective source of energy, whereby diverse forms of work can be purchased to maintain the status quo and synthetic output of the cell. ATP itself is made within the cell from simpler compounds such as glucose and amino acids. In the process of supplying energy, ATP is degraded, losing a phosphate group to become ADP (adenosine diphosphate). The process can be repeated forming AMP (adenosine monophosphate). Sustained mild stress of any kind causes the platelet to do more work to maintain itself and, consequently, this is reflected in a shift in the relative amounts of ATP, ADP and AMP, proportional to the degree of stress. With substantial, but not overwhelming stress, AMP is further degraded to HPYX (hypoxanthine). Hypoxanthine is salvageable to some extent to reform AMP which can also be converted back to ADP and hence, to ATP. Overwhelming stress can deplete the platelet of most of its ATP, converting it to a useless circulating body unable to function or causing it to aggregate to other platelets or foreign surfaces. Web site: http://www.delphion.com/details?pn=US04600696__ •

Simple blood test for diagnosing malignant hyperthermia Inventor(s): Ohnishi; Tsuyoshi (502 King of Prussia Rd., Radnor, PA 19087) Assignee(s): none reported Patent Number: 4,837,163 Date filed: October 2, 1987 Abstract: The invention provides a simple, non-invasive method of screening malignant hyperthermia using a few milliliters of blood drawn from an individual into an acidcitrate anti-coagulant. When blood preservation is not needed, the blood specimen is stored for several hours at room temperature, after which a small amount of blood is taken into a cuvette with the optical path of 0.1 mm. Then, by measuring optical densities at wavelengths of 542 and 578 nm, the susceptibility for malignant hyperthermia can be determined. When a blood specimen has to be shipped to a distant screening center, the specimen can be stored in a styroform container at 0.degree.4.degree. C. with either wet ice or artificial coolant and delivered by an express carrier service. Upon arrival, optical measurement is done in a similar fashion. Excerpt(s): The present invention relates to a new method of diagnosing malignant hyperthermia (MH) using a few milliliters of blood. (i) Functional: The sarcoplasmic reticulum of susceptible pigs is abnormally permeable to calcium, and halothane greatly enhances the calcium release from the sacroplasmic reticulum. Using blood drawn from both MH-positive pigs and MH-positive patients, the inventor found that membranes of red blood cells have structural abnormality similar to that found in the sarcoplasmic reticulum. This is the basis that both sarcoplasmic reticulum and red blood cells may be regulated by the same gene, and that this genetic defect of skeletal muscle could be diagnosed by using red blood cells. Web site: http://www.delphion.com/details?pn=US04837163__

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Use of azumolene for the treatment of malignant hyperthermia Inventor(s): Ellis; Keith O. (Norwich, NY), White, Jr.; Ralph L. (Norwich, NY) Assignee(s): Norwich Eaton Pharmaceuticals, Inc. (Norwich, NY) Patent Number: 4,861,790 Date filed: October 28, 1987 Abstract: The invention involves a method for treating or preventing a malignant hyperthermic reaction in a human or lower animal by administering a safe and effective amount of azumolene. Excerpt(s): This invention is concerned with a method for the treatment of malignant hyperthermia. More particularly, it is concerned with the use of azumolene for the treatment of malignant hyperthermia. The incidence, etiology, clinical manifestations, and management of malignant hyperthermia (MH) are reviewed in Felice-Johnson, J., T. Sudds & G. Bennett, "Malignant Hyperthermia: Current Perspectives", American Journal of Hospital Pharmacy, Vol. 38, No. 5 (May, 1981), pp. 646-651. The syndrome of MH is recognized as one of the causes of anesthesia-related deaths. It is considered pharmacogenetic because both an abnormal gene and precipitating environmental factors are necessary to produce an acute MH reaction. Metabolic defects, involving a derangement of calcium dynamics, appear to be the common characteristic of susceptible individuals. Calcium release and uptake from the sarcoplasmic reticulum is altered when an individual with MH is exposed to certain anesthetic agents or triggering physical and emotional stresses. Muscle rigidity, tachycardia, tachypnea, and high fever can lead to other complications and death. Management of an acute reaction of MH includes cooling methods to lower body temperature, hyperventilation, sodium bicarbonate control of acidosis, maintenance of fluid and electrolyte balance, and administration of dantrolene sodium. The early administration of dantrolene sodium in acute reaction of MH has been shown to rapidly alleviate the symptoms and ensuing severe complications. Web site: http://www.delphion.com/details?pn=US04861790__

Patent Applications on Malignant Hyperthermia As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to malignant hyperthermia: •

Assay for propensity for canine malignant hyperthermia Inventor(s): Brunson, David B.; (Madison, WI), Hogan, Kirk J.; (Madison, WI), Mickelson, James R.; (St. Paul, MN), Roberts, Monica C.; (St. Paul, MN) Correspondence: Quarles & Brady Llp; 411 E. Wisconsin Avenue, Suite 2040; Milwaukee; WI; 53202-4497; US Patent Application Number: 20030104382 Date filed: July 18, 2001

9

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

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Abstract: A method of determining whether a canine is susceptible to canine malignant hyperthermia is disclosed. In one embodiment, this method comprises the step of obtaining a nucleic acid sample from a canine and examining the DNA sample for the presence or absence of a T1640C mutation, wherein the presence of the mutation indicates that the canine is susceptible to canine malignant hyperthermia. Excerpt(s): Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle elicited by exposure to volatile anesthetics and depolarizing muscle relaxants, is well recognized in humans and pigs, although a number of definite episodes have also been reported in dogs.sup.1,2,3,4,5,6,7 When given these agents, MH susceptible (MHS) dogs exhibit tachycardia, hyperthermia, elevated carbon dioxide production, and death if the anesthetic is not discontinued. Specific interventions, including use of the calcium release channel antagonist dantrolene,.sup.8,9 are efficacious in reversing signs of the canine syndrome. In most reports of MH in dogs metabolic acidosis is moderate and muscle rigidity is minimal, in contrast to the severity of both in the swine or human condition. Many additional accounts of episodes resembling MH in dogs within the peri-operative interval,.sup.10,11,12,13- , during exertion,.sup.14,15,16,17 or other chemical exposures.sup.18 have been published. Monitoring and laboratory investigations in these descriptions are scant, and uncertainties persist regarding the incidence of canine MH, as well as its relation to other disorders in the dog, and to MH in other species. In one embodiment, the present invention is a method of determining whether a canine is susceptible to canine malignant hyperthermia. This invention is desirable because one would wish to test for this potentially life-threatening condition prior to surgery on a pet or valuable breeding or research animal. The method preferably comprises the step of obtaining a nucleic acid sample from a canine and examining the sample for the presence or absence of a T1640C mutation, wherein the presence of the mutation indicates that the canine is susceptible to canine malignant hyperthermia. Preferably, the nucleic acid sample is a genomic DNA sample. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with malignant hyperthermia, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “malignant hyperthermia” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on malignant hyperthermia. You can also use this procedure to view pending patent applications concerning malignant hyperthermia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON MALIGNANT HYPERTHERMIA Overview This chapter provides bibliographic book references relating to malignant hyperthermia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on malignant hyperthermia 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: 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 “malignant hyperthermia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “malignant hyperthermia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “malignant hyperthermia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Hyperthermic and Hypermetabolic Disorders: Exertional Heat-Stroke, Malignant Hyperthermia and Related Syndromes by Philip M. Hopkins (Editor), F. R. Ellis (Editor); ISBN: 0521443814; http://www.amazon.com/exec/obidos/ASIN/0521443814/icongroupinterna

Chapters on Malignant Hyperthermia In order to find chapters that specifically relate to malignant hyperthermia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and malignant hyperthermia 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

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search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “malignant hyperthermia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on malignant hyperthermia: •

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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Metabolic Conditions and Nutrition Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 298-309. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: This chapter on metabolic conditions and nutrition is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include inborn errors of metabolism, Suxamethonium (Scoline) sensitivity, malignant hyperthermia (a disorder characterized by a rapid rise in temperature when the patient has a general anesthetic or another drug that can trigger an attack), neuroleptic malignant syndrome, hyperlipoproteinemia (hyperlipidemia), hypolipoproteinemias, the porphyrias, hemochromatosis, homocytinuria, glycogen storage disease (GSD), gingival swelling due to metabolic deposits, dietary disorders, obesity, lactovegetarianism, malnutrition, and pica (the ingestion of unusual objects or

Books

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substances). For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 2 figures. 7 tables. 27 references.

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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 Institute10: •

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

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

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

•

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/

10

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

•

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.11 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:12 •

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

11

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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “malignant hyperthermia” (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 3244 80 879 0 83 4286

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “malignant hyperthermia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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.

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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 malignant hyperthermia 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 malignant hyperthermia. 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 malignant hyperthermia. 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 “malignant hyperthermia”:

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Anesthesia http://www.nlm.nih.gov/medlineplus/anesthesia.html Benign Tumors http://www.nlm.nih.gov/medlineplus/benigntumors.html Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Hodgkin's Disease http://www.nlm.nih.gov/medlineplus/hodgkinsdisease.html Leukodystrophies http://www.nlm.nih.gov/medlineplus/leukodystrophies.html Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Post-Traumatic Stress Disorder http://www.nlm.nih.gov/medlineplus/posttraumaticstressdisorder.html Soft Tissue Sarcoma http://www.nlm.nih.gov/medlineplus/softtissuesarcoma.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 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 malignant hyperthermia. 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

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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: •


•

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

Associations and Malignant Hyperthermia The following is a list of associations that provide information on and resources relating to malignant hyperthermia: •

Canadian Malignant Hyperthermia Association Telephone: (416)340-3238 Fax: (416)340-4960 Email: [email protected] Web Site: http://www.mhacanada.org Background: The Canadian Malignant Hyperthermia Association (Cdn.MHA) is a registered charitable organization dedicated to reducing complications associated with Malignant Hyperthermia. Malignant Hyperthermia is a hereditary disorder in which a person does not react appropriately to certain drugs (e.g., anesthetics) due to a genetic abnormality. Founded in 1976, Cdn.MHA has three main objectives: education, communication, and research. It provides financial support to current test standardization and genetic and lymphocyte research. In addition, the organization also produces educational materials of interest to the general public and medical professionals. Relevant area(s) of interest: Hyperthermia of Anesthesia, Malignant Fever, Malignant Hyperpyrexia, Malignant Hyperthermia

•

Malignant Hyperthermia Association of the United States Telephone: (607) 674-7901 Fax: (607) 674-7910 Email: [email protected] Web Site: http://www.mhaus.org

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Background: The Malignant Hyperthermia Association of the United States is a national not-for-profit voluntary organization dedicated to reducing morbidity and mortality related to malignant hyperthermia. Founded in 1981, the Malignant Hyperthermia Association of the United States seeks to improve the medical care of people with Malignant Hyperthermia and provide support information for people with this rare disorder and their families. It seeks to improve scientific understanding of malignant hyperthermia and promote ongoing medical research related to malignant hyperthermia and other related syndromes. Educational materials produced by the organization include numerous brochures about the disorder, a booklet entitled 'Understanding Malignant Hyperthermia,' a newsletter, and a directory of United States malignant hyperthermia muscle biopsy test centers. Relevant area(s) of interest: Malignant Hyperthermia •

North American Malignant Hyperthermia Registry of MHAUS Telephone: (412) 692-6390 Toll-free: (888) 274-7899 Fax: (412) 692-8658 Email: [email protected] Background: The North American Malignant Hyperthermia Registry is a not-for-profit research organization that is dedicated to acquiring, analyzing, and disseminating patient-specific clinical and laboratory information concerning significantly increased metabolism and muscle injury. Malignant Hyperthermia is an inherited condition characterized by a rapid rise in carbon dioxide production due to increased metabolism in the muscle, followed by increased body temperature and exhaustion of muscle. It occurs most commonly during general anesthesia. Established in 1987, the North American Malignant Hyperthermia Registry maintains a central database of individuals with MH susceptibility and similar syndromes. It can provide physicians with current medical information concerning MH susceptibility status of affected individuals who consent to be registered. The Registry also provides database services to participating MH diagnostic testing referral centers for standardization and validation of MH diagnostic testing procedures. In addition, the Registry investigates the epidemiology of MH to improve diagnosis, treatment, and prevention of MH episodes and gives registered affected individuals the security of knowing that any physician will be able to obtain specific information on their MH susceptibility status. Relevant area(s) of interest: Malignant Hyperthermia

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

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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 “malignant hyperthermia” (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 “malignant hyperthermia”. 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 “malignant hyperthermia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “malignant hyperthermia” (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.21

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

21

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)22: •

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/

22

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, 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

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

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

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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

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

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

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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 malignant hyperthermia: •

Basic Guidelines for Malignant Hyperthermia Malignant hyperthermia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001315.htm

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Signs & Symptoms for Malignant Hyperthermia Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle rigidity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm

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Diagnostics and Tests for Malignant Hyperthermia Biopsy - muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm

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Blood chemistry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm Chem-20 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm CK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm Myoglobin - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003664.htm •

Background Topics for Malignant Hyperthermia Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Central Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.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

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

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

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

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MALIGNANT HYPERTHERMIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [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] Acidemia: Increased acidity of blood. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. [NIH] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from

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carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [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]

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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] 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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This

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is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [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] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the 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] 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] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and

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diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atracurium: A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] 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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific

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combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood Preservation: The process by which blood or its components are kept viable outside of the organism from which they are derived (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] 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] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH]

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Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [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] Cardiac: Having to do with the heart. [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] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU]

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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 Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [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] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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] Cirrhosis: A type of chronic, progressive liver disease. [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] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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,

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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] 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] Compartment Syndromes: Conditions in which increased pressure within a limited space compromises the circulation and function of tissue within that space. Compartmentation involves mainly the leg but also involved are the forearm, arm, thigh, shoulder, and buttock. Some of the causes of increased pressure are trauma, tight dressings, hemorrhage, and exercise. Sequelae include nerve compression, paralysis, and contracture. [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, 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]

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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] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [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] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH]

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Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryoelectron Microscopy: Electron microscopy involving rapid freezing of the samples. The imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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]

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] Dantrolene: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to

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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] Dermal: Pertaining to or coming from the skin. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Diuresis: Increased excretion of urine. [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 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] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Dysgenic: Tending towards racial deterioration, in particular towards a loss of vigour and productiveness. [NIH] Dysostosis: Defective bone formation. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH]

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Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [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] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enoximone: 1,3-Dihydro-4-methyl-5-(4-(methylthio)benzoyl)-2H-imidazol-2-one. A selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with congestive heart failure. [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]

Environmental

Pollutants:

Substances

which

pollute

the

environment.

Use

for

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environmental pollutants in general or for which there is no specific heading. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] 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 and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH]

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Fetoscopy: Endoscopic examination, therapy or surgery of the fetus and amniotic cavity through abdominal or uterine entry. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] 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] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus.

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[EU]

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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [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] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] 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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heat Stroke: A condition characterized by cessation of sweating, hot dry skin, delirium, collapse, and coma and resulting from prolonged exposure to high environmental temperature. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH]

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Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]

Histology: The study of tissues and cells under a microscope. [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 and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of

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water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperpyrexia: Exceptionally high fever either in comparison of the fever usually accompanying a particular disease or absolutely (as in heat stroke). [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypokalemic Periodic Paralysis: Loss or impairment of muscle function or sensation. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [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 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]

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Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [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] 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]

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Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy

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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] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Masseter Muscle: A masticatory muscle whose action is closing the jaws. [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] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH]

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MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motility: The ability to move spontaneously. [EU] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [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 Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fatigue: A state arrived at through prolonged and strong contraction of a muscle.

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Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle. [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] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] 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] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU]

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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, 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] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Blocking Agents: Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (neuromuscular nondepolarizing agents) or noncompetitive, depolarizing agents (neuromuscular depolarizing agents). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. [NIH] Neuromuscular Depolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuromuscular Nondepolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction without causing depolarization of the motor end plate. They prevent acetylcholine from triggering muscle contraction and are used as muscle relaxants during electroshock treatments, in convulsive states, and as anesthesia adjuvants. [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] Neurophysiology: The scientific discipline concerned with the physiology 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] 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]

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Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [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] Nurse Anesthetists: Professional nurses who have completed postgraduate training in the administration of anesthetics and who function under the responsibility of the operating surgeon. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or

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concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] 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] Paralysis: Loss of ability to move all or part of the body. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Simulation: The use of persons coached to feign symptoms or conditions of real diseases in a life-like manner in order to teach or evaluate medical personnel. [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] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] 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] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] 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] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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] Phosphorylation: The introduction of a phosphoryl group into a compound through the

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formation of an ester bond between the compound and a phosphorus moiety. [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]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Postoperative: After surgery. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] 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

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another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein 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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.

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[NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [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

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elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [NIH]

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Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU]

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Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Succinylcholine: A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. [NIH]

Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] 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] Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermogenesis: The generation of heat in order to maintain body temperature. The uncoupled oxidation of fatty acids contained within brown adipose tissue and shivering are examples of thermogenesis in mammals. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Topical: On the surface of the body. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH]

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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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [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] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are

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not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]

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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]

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INDEX A Abdominal, 99, 112, 123 Acceptor, 99, 117, 122 Acetylcholine, 99, 121 Acidemia, 68, 99 Acidity, 99 Acidosis, 71, 99 Actin, 99, 119, 120, 130 Adenine, 99 Adenosine, 69, 70, 99, 104, 115, 123 Adenosine Diphosphate, 69, 70, 99 Adenosine Monophosphate, 69, 70, 99 Adenosine Triphosphate, 69, 70, 99, 123 Adipose Tissue, 99, 129 Adrenal Medulla, 99, 111, 122 Adrenaline, 33, 99 Adrenergic, 5, 99, 102, 109, 111, 129 Aerobic, 68, 99, 100, 122 Aerobic Metabolism, 68, 99, 100, 122 Aerobic Respiration, 100, 122 Affinity, 100, 117, 127 Agar, 100, 124 Agonist, 22, 53, 100, 109, 111 Alertness, 100, 104 Algorithms, 100, 103 Alkaline, 99, 100, 104 Alkaloid, 100, 105, 119, 126 Alleles, 50, 100 Alternative medicine, 100 Amino acid, 6, 10, 19, 70, 100, 101, 108, 112, 113, 114, 115, 123, 124, 125, 127, 129, 130 Amino Acid Sequence, 10, 100, 101, 112 Amphetamines, 101, 106 Anaesthetic, 13, 14, 47, 59, 101 Analgesic, 101, 119, 122 Analogous, 101, 109, 130 Anesthetics, 4, 7, 29, 53, 66, 67, 68, 72, 87, 101, 111, 122 Anions, 101, 116 Antagonism, 101, 104 Antibodies, 10, 101, 117, 124 Antibody, 10, 68, 100, 101, 106, 111, 114, 116, 118, 128 Antigen, 100, 101, 106, 114, 116, 118 Antioxidant, 63, 101, 122 Antipsychotic, 101, 121 Aorta, 102, 104, 131

Apathy, 102, 121 Aplasia, 102, 110 Aqueous, 102, 108 Arterial, 102, 115, 125 Arteries, 102, 103, 107, 119 Arterioles, 102, 103 Artery, 14, 69, 102, 103, 107, 111, 129, 131 Assay, 9, 71, 102 Atracurium, 53, 102 Atrium, 102, 104, 119, 131 Atypical, 14, 25, 102 B Bacteria, 101, 102, 118, 119, 124, 127, 128, 130 Bactericidal, 102, 111 Bacteriophage, 102, 124, 130 Bile, 102, 117 Binding Sites, 6, 102 Biochemical, 7, 13, 30, 38, 100, 103, 127 Biopsy, 14, 22, 26, 33, 40, 59, 88, 97, 103 Biopsy specimen, 59, 103 Biotechnology, 10, 11, 81, 103 Bladder, 103, 115, 121, 131 Blood Coagulation, 103, 104 Blood Platelets, 69, 103, 118, 127, 129 Blood Preservation, 70, 103 Blood pressure, 103, 104, 115, 127 Blood vessel, 69, 103, 104, 105, 123, 127, 128, 129, 131 Body Fluids, 103, 104, 127 Bolus, 40, 103 Bolus infusion, 103 Bone Marrow, 69, 103, 117, 118, 128 Bone Marrow Cells, 69, 103, 118 Bowel, 103, 121 Breeding, 72, 103 Bronchi, 103, 111 Bypass, 14, 104 C Caffeine, 16, 17, 22, 25, 26, 34, 35, 42, 48, 50, 52, 58, 59, 104 Calcium, 5, 8, 10, 16, 18, 24, 26, 27, 28, 29, 30, 32, 34, 37, 41, 45, 53, 54, 58, 59, 66, 67, 68, 70, 71, 72, 104, 106, 116, 125, 126, 130 Calcium Channels, 8, 104 Calmodulin, 4, 8, 9, 104, 116 Carbohydrates, 100, 104, 105, 122

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Carbon Dioxide, 48, 68, 72, 88, 104, 115, 126 Cardiac, 4, 5, 7, 9, 68, 104, 111, 113, 114, 120 Cardiopulmonary, 20, 104 Cardiopulmonary Bypass, 20, 104 Cardiovascular, 5, 66, 102, 104, 127 Cardiovascular disease, 5, 104 Case report, 21, 23, 47, 51, 54, 104 Cations, 104, 116 Caudal, 104, 124 Cell Division, 102, 105, 119, 124, 127 Cell membrane, 23, 104, 105, 109, 116, 123, 131 Cell Respiration, 100, 105, 122, 126 Central Nervous System, 99, 101, 104, 105, 106, 111, 113, 119, 127 Cerebral, 105, 108, 110, 111, 125 Cerebrovascular, 104, 105 Cerebrum, 105, 130 Chimeras, 8, 105 Chin, 105, 118 Cholesterol, 102, 105, 107, 115 Chromosomal, 74, 105, 124 Chromosome, 21, 24, 28, 30, 31, 37, 38, 105, 117, 127 Chronic, 35, 36, 105, 110, 116, 128 Chronic renal, 35, 105 Cirrhosis, 105, 113 Cleft Lip, 74, 105 Clinical trial, 3, 81, 105, 125 Cloning, 67, 68, 103, 105 Coca, 105 Cocaine, 22, 25, 105 Cofactor, 106, 125 Cognition, 106, 121 Collagen, 69, 100, 106, 125 Collapse, 106, 113 Compartment Syndromes, 53, 106 Complement, 106, 107, 112, 118 Complementary and alternative medicine, 61, 64, 106 Complementary medicine, 61, 107 Compress, 107, 129 Computational Biology, 81, 107 Computer Simulation, 21, 107 Concomitant, 67, 107 Conduction, 107, 121 Confusion, 107, 109, 115, 121, 131 Congenita, 107, 110 Congestive heart failure, 107, 110 Connective Tissue, 103, 106, 107, 112, 128

Consciousness, 69, 101, 107, 108 Constriction, 107, 131 Constriction, Pathologic, 107, 131 Contraindications, ii, 107 Convulsive, 107, 110, 121 Coronary, 14, 69, 104, 107, 119 Coronary heart disease, 104, 107 Coronary Thrombosis, 107, 119 Creatine, 18, 29, 35, 53, 61, 108 Creatine Kinase, 29, 35, 53, 108 Creatinine, 108 Crossing-over, 108, 126 Cryoelectron Microscopy, 9, 108 Curare, 62, 108, 120 Cyanosis, 68, 108, 114 Cyclic, 104, 108, 123 Cysteine, 9, 108 Cystine, 108 Cytoplasm, 10, 105, 108, 116, 126 D Dantrolene, 4, 7, 14, 32, 44, 66, 71, 72, 108 Deletion, 50, 108 Delirium, 52, 102, 108, 113 Dental Care, 108, 123 Depolarization, 10, 109, 121 Dermal, 109, 110 Diabetes Mellitus, 26, 109, 113, 114 Diagnostic procedure, 65, 109 Digestion, 66, 102, 103, 109, 117 Direct, iii, 4, 67, 109, 120, 126, 129 Discrete, 8, 109 Disinfectant, 109, 111 Disorientation, 107, 108, 109 Disposition, 20, 50, 109 Diuresis, 104, 109 Dopamine, 102, 106, 109, 121 Dorsal, 109, 124 Drug Design, 8, 109 Dysgenic, 8, 109 Dysostosis, 74, 109 Dystrophin, 109, 120 E Ectoderm, 109, 110 Ectodermal Dysplasia, 74, 110 Effector, 4, 99, 106, 110, 123 Efficacy, 109, 110 Elastic, 110, 129 Elastin, 106, 110 Electrolyte, 71, 108, 110, 114, 124, 127 Electrons, 101, 110, 116, 118, 122, 126 Electroshock, 110, 121 Elementary Particles, 110, 118, 125

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Encephalocele, 110, 121 Endogenous, 8, 109, 110 End-stage renal, 105, 110 Energy balance, 16, 110 Enoximone, 22, 110 Environmental Health, 80, 82, 110 Environmental Pollutants, 110, 124 Enzymatic, 100, 104, 106, 111 Enzyme, 66, 109, 110, 111, 117, 118, 119, 123, 125, 129, 131 Ephedrine, 33, 111 Epidermis, 110, 111 Epinephrine, 69, 99, 109, 111, 121, 122 Epitope, 10, 111 Erythrocytes, 103, 111, 126 Ethanol, 25, 111 Evoke, 111, 128 Excitation, 4, 5, 6, 8, 10, 18, 101, 108, 111, 121 Exhaustion, 88, 101, 111 Exogenous, 110, 111, 123 Extracellular, 9, 107, 111, 127 F Facial, 74, 111 Family Planning, 74, 81, 111 Fat, 99, 103, 107, 111, 117, 124, 128, 130 Fatigue, 111, 113, 120 Femoral, 26, 104, 111 Femoral Artery, 104, 111 Fetal Development, 111, 121 Fetoscopy, 42, 112 Fetus, 111, 112 Fibrinogen, 112, 129 Fibrosis, 74, 107, 112 Fixatives, 108, 112 Fluorescence, 7, 9, 112 Forearm, 103, 106, 112 Fossa, 13, 112 Free Radicals, 101, 112 G Gas, 104, 112, 114, 121, 126 Gastrointestinal, 111, 112, 127, 129 Gastrointestinal tract, 111, 112, 127 Genetic Code, 112, 122 Genetic Engineering, 103, 105, 112 Genetic testing, 28, 39, 40, 48, 112 Genotype, 21, 29, 32, 59, 112, 123 Gland, 99, 112, 123, 126, 128 Glomerular, 112, 126 Glucose, 70, 109, 113, 114, 115, 116 Glucose Intolerance, 109, 113 Glycine, 100, 113, 121

Glycogen, 68, 74, 113, 120 Glycogen Storage Disease, 74, 113 Glycolysis, 67, 113 Glycoproteins, 104, 113, 116 Glycosaminoglycans, 113, 119 Governing Board, 113, 124 Graft, 50, 113 Grafting, 14, 113 H Haplotypes, 19, 21, 113 Headache, 104, 113, 115 Heart attack, 69, 104, 113 Heart failure, 6, 68, 111, 113 Heat Stroke, 12, 113, 115 Hemochromatosis, 74, 113 Hemodialysis, 114, 130 Hemofiltration, 18, 114, 130 Hemoglobin, 108, 111, 114 Hemoglobin M, 108, 114 Hemorrhage, 106, 113, 114, 128 Hemostasis, 114, 127 Hepatic, 108, 114 Hereditary, 87, 110, 114 Heredity, 112, 114 Heterogeneity, 23, 28, 100, 114 Histology, 40, 114 Homeostasis, 4, 6, 27, 34, 114 Homologous, 8, 100, 108, 114, 127 Hormone, 99, 111, 114 Hybrid, 6, 114 Hydrogen, 99, 104, 114, 117, 119, 120, 122, 125 Hydrolysis, 114, 124, 125 Hydroxylysine, 106, 115 Hydroxyproline, 100, 106, 115 Hypercapnia, 23, 115 Hyperlipidemia, 74, 115 Hyperlipoproteinemia, 74, 115 Hyperpyrexia, 59, 62, 87, 115 Hypertension, 104, 113, 115 Hyperventilation, 71, 115 Hypoglycaemia, 108, 115 Hypokalemic Periodic Paralysis, 9, 41, 115 Hypoplasia, 110, 115 Hypoxanthine, 69, 70, 115 Hypoxia, 66, 108, 115 I Idiopathic, 37, 115 Immune system, 115, 117, 131 Impairment, 108, 115, 118 In situ, 4, 115

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In vitro, 7, 13, 14, 15, 20, 21, 31, 33, 40, 42, 46, 48, 49, 50, 51, 53, 58, 59, 115 In vivo, 7, 33, 115 Incision, 115, 116 Incisor, 74, 115 Incontinence, 111, 115 Infarction, 107, 116, 119 Infection, 49, 108, 116, 117, 128, 131 Inflammation, 112, 116, 124, 126 Infusion, 26, 116 Ingestion, 25, 62, 74, 116, 124 Inhalation, 67, 116, 117, 124 Inositol, 32, 34, 63, 116 Inositol 1,4,5-Trisphosphate, 63, 116 Inotropic, 109, 110, 116 Insight, 8, 116 Interstitial, 116, 126 Intoxication, 52, 108, 116, 131 Intracellular, 4, 6, 7, 10, 16, 30, 34, 66, 104, 116, 117, 124, 126 Intramuscular, 16, 116 Intravenous, 98, 116 Invasive, 70, 116, 117 Involuntary, 116, 120, 127, 128 Ion Channels, 10, 116 Ions, 13, 53, 59, 99, 104, 110, 114, 116, 119, 125, 126 Isoenzyme, 108, 117 Isoflurane, 51, 117 K Kb, 67, 80, 117 Kinetics, 7, 22, 104, 117 L Latent, 117, 125 Lesion, 69, 117 Leukocytes, 103, 117 Ligaments, 107, 117 Ligands, 6, 8, 10, 117 Linkage, 28, 37, 117 Lip, 105, 117 Lipid, 5, 9, 29, 62, 117, 122, 130 Lipid Bilayers, 5, 9, 29, 117 Lipid Peroxidation, 117, 122 Lipophilic, 117, 124 Liver, 68, 99, 102, 105, 113, 114, 117 Localization, 24, 37, 38, 117 Localized, 8, 109, 116, 117, 124 Lymphatic, 116, 117 Lymphocyte, 27, 87, 101, 117, 118 Lymphoid, 101, 117 Lymphoma, 15, 86, 117 Lysosomal Storage Diseases, 117, 119

M Magnetic Resonance Imaging, 117, 118 Magnetic Resonance Spectroscopy, 33, 118 Major Histocompatibility Complex, 113, 118 Malformation, 12, 118 Malnutrition, 74, 118 Masseter Muscle, 35, 118 Masticatory, 118 Maxillary, 105, 118 Medial, 105, 118 Mediate, 10, 109, 118 Mediator, 118, 127 MEDLINE, 81, 118 Megakaryocytes, 103, 118 Membrane, 4, 8, 10, 27, 62, 105, 106, 109, 116, 118, 122, 123, 126 Memory, 108, 118 Mental, iv, 3, 74, 80, 82, 105, 106, 107, 108, 109, 111, 118, 125, 126, 131 Mental Retardation, 74, 118 Mesoderm, 105, 118 Metabolic acidosis, 72, 118 Metabolic disorder, 113, 118 MI, 98, 119 Microbe, 119, 130 Microbiology, 102, 119 Microorganism, 106, 119, 131 Migration, 105, 119 Mitosis, 10, 119 Mitral Valve, 20, 119 Modeling, 14, 109, 119 Modification, 100, 112, 119 Modulator, 9, 119 Molecular mass, 10, 119 Molecular Structure, 119, 130 Molecule, 67, 101, 103, 106, 110, 111, 114, 119, 122, 124, 126 Morphine, 55, 119, 120, 122 Motility, 15, 119, 127 Motor nerve, 119, 120 Mucopolysaccharidoses, 74, 119 Muscle Contraction, 4, 109, 119, 121, 126 Muscle Fatigue, 5, 119 Muscle Fibers, 8, 13, 26, 54, 66, 120, 130 Muscle Proteins, 8, 120 Muscle relaxant, 4, 66, 67, 68, 72, 108, 120, 121, 129 Muscle Relaxation, 120, 121, 129 Muscle tension, 120 Mutagenesis, 5, 120

137

Mutagens, 120 Myalgia, 49, 120 Myocardium, 119, 120 Myopathy, 18, 34, 36, 40, 46, 53, 68, 120 Myosin, 119, 120, 130 N Narcolepsy, 111, 120 Narcotic, 119, 120 Necrosis, 116, 119, 120, 126 Neoplastic, 117, 120 Nerve, 16, 22, 28, 32, 41, 58, 99, 101, 105, 106, 118, 119, 120, 121, 128, 130 Nervous System, 105, 118, 120, 121, 129 Neural, 74, 110, 120, 121 Neural tube defects, 74, 121 Neuroleptic, 35, 41, 42, 74, 101, 121 Neuromuscular, 5, 7, 18, 32, 34, 45, 61, 62, 99, 102, 108, 121 Neuromuscular Blockade, 62, 121 Neuromuscular Blocking Agents, 61, 102, 121 Neuromuscular Depolarizing Agents, 121 Neuromuscular Junction, 99, 121 Neuromuscular Nondepolarizing Agents, 121 Neuronal, 10, 104, 121 Neurons, 106, 120, 121, 129 Neurophysiology, 109, 121 Neurotransmitter, 99, 100, 109, 113, 116, 121, 122, 129 Nitrogen, 100, 119, 121, 130 Norepinephrine, 99, 109, 111, 121, 122 Nuclei, 110, 112, 118, 119, 122, 125 Nucleic acid, 72, 112, 115, 120, 121, 122 Nucleus, 108, 110, 122, 125 Nurse Anesthetists, 53, 122 O Ophthalmic, 13, 122 Opiate, 119, 122 Opium, 119, 122 Oral Health, 74, 122 Organelles, 108, 122 Outpatient, 35, 44, 122 Oxidation, 5, 99, 101, 108, 114, 117, 122, 129 Oxidative metabolism, 100, 122 Oxidative Stress, 5, 122 Oxygen Consumption, 110, 122, 126 Oxygenator, 104, 122 P Paediatric, 13, 54, 122 Palate, 74, 123

Pancreas, 99, 113, 123 Paralysis, 32, 37, 106, 108, 123 Pathogenesis, 28, 123 Pathologic, 99, 103, 107, 112, 123 Patient Simulation, 53, 123 Pediatric Dentistry, 74, 123 Pedigree, 19, 20, 21, 37, 51, 123 Peptide, 100, 123, 124, 125 Perfusion, 115, 123 Perioperative, 14, 45, 123 Pharmacokinetics, 109, 123 Pharmacologic, 6, 7, 101, 123, 130 Phenotype, 7, 21, 29, 31, 32, 50, 123 Phosphodiesterase, 22, 110, 123 Phospholipids, 111, 116, 123 Phosphorus, 104, 123, 124 Phosphorylation, 5, 123 Physiologic, 4, 100, 111, 124, 126, 127 Physiology, 4, 9, 22, 30, 34, 58, 121, 124 Plants, 100, 103, 104, 105, 113, 122, 124, 130 Plaque, 69, 124 Plasma, 8, 27, 69, 101, 105, 109, 112, 113, 114, 115, 124, 125 Plasma cells, 101, 124 Plasmid, 67, 124 Platelets, 30, 69, 124, 129 Pneumonia, 107, 124 Poisoning, 108, 116, 124 Polychlorinated Biphenyls, 6, 124 Polymorphism, 67, 124 Polypeptide, 100, 106, 112, 124, 125 Posterior, 13, 109, 123, 124 Postoperative, 19, 46, 124 Potassium, 68, 124 Practice Guidelines, 82, 124 Precursor, 109, 110, 111, 122, 124, 125, 130 Predisposition, 15, 49, 67, 125 Probe, 9, 125 Progression, 70, 125 Progressive, 69, 105, 119, 120, 125, 126 Proline, 106, 115, 125 Prophylaxis, 44, 125 Propofol, 26, 47, 59, 125 Protein C, 101, 102, 120, 125, 130 Protein Conformation, 101, 125 Protein S, 5, 103, 112, 125 Proteolytic, 66, 106, 112, 125 Prothrombin, 125, 129 Protocol, 17, 33, 125 Protons, 114, 118, 125, 126 Psychic, 118, 125, 127

138


Psychomotor, 108, 110, 121, 125 Public Policy, 81, 125 Publishing, 11, 125 Pulmonary, 103, 114, 115, 126, 131 Pulmonary Ventilation, 115, 126 Q Quaternary, 125, 126, 129 R Radiation, 110, 112, 115, 126 Receptors, Serotonin, 126, 127 Recombinant, 4, 8, 10, 34, 67, 126 Recombination, 28, 126 Red blood cells, 70, 111, 126 Refer, 1, 106, 117, 121, 126 Relaxant, 126, 129 Renal failure, 21, 46, 108, 126 Respiration, 104, 108, 126 Retrograde, 7, 9, 126 Rhabdomyolysis, 12, 18, 19, 21, 23, 25, 26, 38, 45, 49, 50, 68, 126 Rhinitis, 111, 126 Ribose, 99, 126 S Sarcoplasmic Reticulum, 4, 8, 10, 11, 13, 26, 53, 58, 66, 70, 71, 126 Schizophrenia, 34, 126, 131 Screening, 24, 25, 43, 59, 70, 105, 126 Secretion, 10, 126 Segregation, 17, 37, 126, 127 Seizures, 108, 127 Sensibility, 101, 127 Sepsis, 118, 127 Sequencing, 19, 127 Serotonin, 14, 45, 50, 102, 121, 126, 127, 130 Serum, 29, 53, 106, 108, 127 Shivering, 127, 129 Shock, 110, 127, 130 Side effect, 102, 117, 127, 130 Signs and Symptoms, 7, 127 Skeleton, 99, 127 Skull, 110, 121, 127 Smooth muscle, 101, 104, 119, 127, 128, 129 Sodium, 37, 71, 127 Sodium Bicarbonate, 71, 127 Soft tissue, 103, 127, 128 Solvent, 111, 128 Somatic, 119, 128 Somatic cells, 119, 128 Spasm, 30, 35, 51, 107, 128 Specialist, 89, 128

Species, 72, 108, 111, 114, 119, 128, 129, 130, 131 Specificity, 52, 100, 104, 128 Spectrum, 119, 128 Sperm, 105, 128 Spina bifida, 121, 128 Spinal cord, 105, 120, 121, 128 Stimulant, 104, 128 Stimulus, 58, 111, 116, 128, 129 Stress, 36, 63, 66, 68, 69, 86, 110, 122, 125, 128 Stroke, 69, 73, 80, 104, 128 Stromal, 103, 128 Stromal Cells, 103, 128 Subacute, 116, 128 Subclinical, 116, 127, 128 Subspecies, 128, 129 Substance P, 127, 129 Succinylcholine, 16, 30, 67, 129 Supplementation, 61, 63, 129 Suppression, 4, 129 Sympathomimetic, 109, 111, 122, 129 Synapse, 99, 121, 129, 130 Systemic, 102, 103, 108, 111, 116, 127, 129 T Tachycardia, 71, 72, 129 Tachypnea, 71, 129 Thermal, 68, 129 Thermogenesis, 68, 129 Thigh, 106, 111, 129 Threshold, 26, 115, 129 Thrombin, 69, 112, 125, 129 Thrombocytes, 124, 129 Thrombocytopenia, 52, 129 Thrombosis, 125, 128, 129 Topical, 111, 127, 129 Tourniquet, 25, 129 Toxic, iv, 108, 123, 124, 130 Toxicity, 50, 130 Toxicology, 82, 130 Toxins, 101, 104, 116, 130 Transduction, 116, 130 Transfection, 103, 130 Translation, 100, 130 Transmitter, 99, 109, 116, 118, 122, 130 Transplantation, 46, 50, 105, 118, 130 Trauma, 39, 106, 108, 113, 120, 130 Tricyclic, 54, 130 Triglyceride, 115, 130 Tropomyosin, 120, 130 Troponin, 120, 130 Tryptophan, 106, 127, 130

139

Tuberous Sclerosis, 74, 130 U Ultrafiltration, 114, 130 Unconscious, 101, 130 Uremia, 126, 130 Urethra, 131 Urinary, 111, 115, 131 Urine, 98, 103, 108, 109, 115, 131 V Vascular, 20, 68, 69, 116, 131 Vasoconstriction, 68, 111, 131 Veins, 103, 131 Venous, 18, 125, 131 Ventricle, 119, 131 Venules, 103, 131

Veterinary Medicine, 81, 131 Viral, 36, 130, 131 Virulence, 130, 131 Virus, 102, 112, 124, 130, 131 Vitamin A, 116, 131 Vitro, 131 Vivo, 46, 131 Voltage-gated, 8, 131 W Wakefulness, 108, 131 White blood cell, 101, 117, 124, 131 Withdrawal, 108, 131 Y Yeasts, 123, 132

140


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