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

TITIS EDIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

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TITIS EDIA 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., 1960Otitis Media: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84142-X 1. Otitis Media-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 otitis media. 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 OTITIS MEDIA ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Otitis Media................................................................................ 32 E-Journals: PubMed Central ....................................................................................................... 88 The National Library of Medicine: PubMed ................................................................................ 93 CHAPTER 2. NUTRITION AND OTITIS MEDIA ............................................................................... 139 Overview.................................................................................................................................... 139 Finding Nutrition Studies on Otitis Media............................................................................... 139 Federal Resources on Nutrition ................................................................................................. 145 Additional Web Resources ......................................................................................................... 145 CHAPTER 3. ALTERNATIVE MEDICINE AND OTITIS MEDIA ......................................................... 147 Overview.................................................................................................................................... 147 National Center for Complementary and Alternative Medicine................................................ 147 Additional Web Resources ......................................................................................................... 154 General References ..................................................................................................................... 156 CHAPTER 4. DISSERTATIONS ON OTITIS MEDIA ........................................................................... 157 Overview.................................................................................................................................... 157 Dissertations on Otitis Media.................................................................................................... 157 Keeping Current ........................................................................................................................ 159 CHAPTER 5. CLINICAL TRIALS AND OTITIS MEDIA ...................................................................... 161 Overview.................................................................................................................................... 161 Recent Trials on Otitis Media.................................................................................................... 161 Keeping Current on Clinical Trials ........................................................................................... 163 CHAPTER 6. PATENTS ON OTITIS MEDIA ...................................................................................... 165 Overview.................................................................................................................................... 165 Patents on Otitis Media............................................................................................................. 165 Patent Applications on Otitis Media ......................................................................................... 187 Keeping Current ........................................................................................................................ 194 CHAPTER 7. BOOKS ON OTITIS MEDIA ......................................................................................... 195 Overview.................................................................................................................................... 195 Book Summaries: Federal Agencies............................................................................................ 195 Book Summaries: Online Booksellers......................................................................................... 197 The National Library of Medicine Book Index ........................................................................... 199 Chapters on Otitis Media........................................................................................................... 200 CHAPTER 8. MULTIMEDIA ON OTITIS MEDIA ............................................................................... 209 Overview.................................................................................................................................... 209 Video Recordings ....................................................................................................................... 209 Bibliography: Multimedia on Otitis Media ............................................................................... 211 CHAPTER 9. PERIODICALS AND NEWS ON OTITIS MEDIA ............................................................ 213 Overview.................................................................................................................................... 213 News Services and Press Releases.............................................................................................. 213 Newsletter Articles .................................................................................................................... 218 Academic Periodicals covering Otitis Media ............................................................................. 218 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 221 Overview.................................................................................................................................... 221 U.S. Pharmacopeia..................................................................................................................... 221 Commercial Databases ............................................................................................................... 223 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 227 Overview.................................................................................................................................... 227

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NIH Guidelines.......................................................................................................................... 227 NIH Databases........................................................................................................................... 229 Other Commercial Databases..................................................................................................... 232 The Genome Project and Otitis Media....................................................................................... 232 APPENDIX B. PATIENT RESOURCES ............................................................................................... 237 Overview.................................................................................................................................... 237 Patient Guideline Sources.......................................................................................................... 237 Finding Associations.................................................................................................................. 246 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 249 Overview.................................................................................................................................... 249 Preparation................................................................................................................................. 249 Finding a Local Medical Library................................................................................................ 249 Medical Libraries in the U.S. and Canada ................................................................................. 249 ONLINE GLOSSARIES................................................................................................................ 255 Online Dictionary Directories ................................................................................................... 258 OTITIS MEDIA DICTIONARY.................................................................................................. 261 INDEX .............................................................................................................................................. 339

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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 otitis media 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 otitis media, 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 otitis media, 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 otitis media. 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 otitis media, 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 otitis media. 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 OTITIS MEDIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on otitis media.

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

Otitis Media and Language Development: A Meta-Analysis Source: American Journal of Speech-Language Pathology. 10(1): 65-80. February 2001. Contact: Available from American Speech-Language-Hearing Association (ASHA). Subscription Sales Coordinator, 10801 Rockville Pike, Rockville, MD 20852-3279. (888) 498-6699. Fax (301) 897-7358. Website: www.asha.org. Summary: A substantial contemporary research literature on the impact of otitis media (middle ear infection) with effusion (OME) on language development in young children currently exists. Compared to the reports of earlier retrospective research on the topic, the results of the more recent prospective studies may be viewed as less conclusive and more equivocal. However, the negative impact of OME on young children's language development appears to be a widely held belief. This article reports on a project that

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used the methodology of meta analysis on this body of literature. The results of this meta analysis show that the magnitude of the statistical population effect of OME is markedly low. Nevertheless, the authors note that the findings of low population effects in this meta analysis may be related to certain aspects of the primary research. Among these factors are failure to determine research participants' hearing levels, other intrinsic or extrinsic individual differences among the research participants, as well as the sensitivity of language measures used. The authors remind readers that their research was limited to an examination of the relationship of OME to young children's speech perception or speech production, and conclusions based on the results of this meta analysis should not be extended to those domains of oral language performance. One clear clinical implication of this meta analysis is that children suspected of having OME must have more attention paid to their hearing abilities, and important aspects of quality of life, in addition to the evaluation and diagnosis of OME. 1 figure. 4 tables. 75 references. •

Acute Otitis Media: Part I. Improving Diagnostic Accuracy Source: American Family Physician. 61(7): 2051-2056. April 1, 2000. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: According to the author of this journal article on diagnostic accuracy, acute otitis media (AOM) is overdiagnosed. Symptoms are neither sensitive nor specific for the diagnosis of otitis media (middle ear infection); fever and ear pain are present in only one half of patients. Undue reliance on one feature (redness of the tympanic membrane, or eardrum) and failure to assess tympanic membrane mobility with pneumatic otoscopy contribute to inaccurate diagnoses. Adequate visualization of the tympanic membrane is often impaired by low light output from old otoscope bulbs and blockage of the ear canal by cerumen (earwax). Distinguishing AOM from otitis media with effusion (OME) is clinically important because antibiotics are seldom indicated for the latter condition. A key differentiating feature is the position of the tympanic membrane: it is usually bulging in AOM and in a neutral position or a retracted position in OME. Tympanometry and acoustic reflectometry can be useful adjunctive tools to confirm the presence of fluid in the middle ear. Selective use of tympanocentesis (surgical drainage of fluid) in cases of refractory or recurrent middle ear disease can help guide appropriate therapy and avoid unnecessary medical or surgical interventions. 3 tables. 23 references.

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Options for Treating Otitis Media Source: Practitioner. 240(1558): 42-47. January 1996. Summary: According to this article on the management of patients with otitis media, a key problem in otitis media (middle ear infection) is that the diagnosis is often unclear, and that management can be difficult and apparently illogical. Topics covered include how to recognize the types of otitis media, determining the indications for antibiotics, and patient referral. The article concludes with a discussion on persistent middle ear effusion. As this problem can lead to delay in speech and educational difficulties (if the condition persists beyond two to three months), the patient should be referred for consideration of insertion of grommets. While waiting, a trial of cephalosporin may clear the effusion and, if effective, may make surgery unnecessary. Guidelines for otological referral include: recurrent episodes of acute suppurative otitis media unaffected by chemoprophylaxis; recurrent episodes of acute otitis media with or

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without effusion despite adequate medical treatment; associated hearing loss of greater than 25 to 30 dB; presence of speech or language delay associated with recurrent otitis media in any of its forms; presence of persistent perforation of the tympanic membrane with or without the suspicion of cholesteatoma; and suppurative complications in acute suppurative otitis media, such as acute mastoiditis or chronic suppurative otitis media. 3 figures. 10 references. •

Diagnosis and Pharmacological Management of Acute Otitis Media Source: Pediatric Nursing. 23(5): 423-429. September-October 1998. Contact: Available from Anthony Jannetti Publications, Inc. East Holly Avenue, Box 56, Pitman, NJ 08071. Summary: Acute otitis media (AOM) is one of the most commonly diagnosed problems by primary care providers. This article reviews the diagnosis and pharmacological management of AOM. Diagnosis of AOM is based upon positive physical findings of a full or bulging tympanic membrane (TM), absent or obscured bony landmarks, distorted or absent light reflex, and decreased or absent mobility of the TM. Prevention through education and early detection of AOM are the best methods for avoiding serious complications and sequelae. The antibiotics available for treatment of AOM are extensive. Treatment of AOM should be based upon clinical diagnosis and current research based options for treatment. The authors briefly consider the controversy over antibiotic use, much of which concerns the need for using new antibiotics to combat antibiotic resistant bacteria. Parent education is crucial in prevention and treatment efforts. One table presents a practice protocol for otitis media. 2 tables. 28 references.

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Acute Otitis Media: Bacteriology and Bacterial Resistance in 205 Pediatric Patients Source: International Journal of Pediatric Otorhinolaryngology. 56(1): 23-31. November 30, 2000. Contact: Available from Elsevier Science. P.O. Box 945, New York, NY 10159-0945. (888) 437-4636. Fax (212) 633-3680. E-mail: [email protected]. Summary: Acute otitis media (AOM, middle ear infection) is one of the most frequent diagnoses in children below the age of 2 years. Treatment is usually based on information included in the literature concerning bacteriology. This article reports on work undertaken to define the most frequent germs in the etiology (cause) of AOM in pediatric patients in Argentina. Cultures in middle ear secretions obtained through tympanocentesis (eardrum sampling) were tested in 205 patients. The results obtained were similar to those published in previous reports in which Streptococcus pneumoniae and Haemophilus influenzae proved to be the predominant germs. However, there are certain discrepancies concerning the incidence of Moraxella catarrhalis and this has a direct impact on the total percent of resistant strains, thus modifying treatment approaches for the therapy of AOM. The authors also studied the antibiotic sensitivity profiles of the most frequent etiologic agents. 4 figures. 5 tables. 24 references.

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Role of Viruses in the Pathogenesis of Acute Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S17-S23. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com.

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Summary: Although acute otitis media (AOM, middle ear infection) is generally considered a bacterial infection and therefore usually treated with antibiotics, pathogenic bacteria can be isolated from the middle ear fluid (MEF) in approximately 70 percent of cases of AOM. The fact that about one third of AOM cases remain without a proven bacterial etiology, together with vast clinical experience connecting AOM with viral upper respiratory tract infections (URIs) has prompted investigators to search for the role of viruses in the pathogenesis of this condition. This article reports on some of the convincing evidence available to support the crucial role of respiratory viruses in the development of AOM. The author covers epidemiology, Eustachian tube dysfunction, alteration of the host's immune defense, the effect of viral infection on bacterial colonization and adherence, the presence of viruses in MEF, and viral vaccines in the prevention of AOM. The author concludes that respiratory viral infection appears to initiate the cascade of events that finally leads to the development of AOM (this progression is summarized in a chart). The pathogenesis of AOM is complicated, involving a network of factors, some probably not yet identified, which affect each other in a time dependent manner. 1 figure. 1 table. 75 references. •

Acute Otitis Media in Children: What Next When First-Line Therapy Fails? Source: Consultant. 38(11): 2681-2684, 2687-2690. November 1998. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. (203) 661-0600. Summary: Although amoxicillin continues to be the drug of first choice for patients with acute otitis media (AOM), the presence of drug-resistant pathogens may cause treatment failure. This article outlines strategies to be employed when first line therapy fails in children with AOM. Streptococcus pneumoniae is the most common pathogen found in middle ear fluid (MEF), followed by Hemophilus influenzae and Moraxella catarrhalis. Beta-lactamase inhibitors, such as clavulanate, are effective against H. influenzae and M. catarrhalis, but not against penicillin-resistant pneumococci. Trimethoprimsulfamethoxazole (TMP-SMX) and azithromycin show high levels of activity against all three common pathogens, as measured by their concentrations in MEF. The author concludes that azithromycin, amoxicillin and clavulanate combinations, and TMP-SMX appear to be reasonable choices for second-line treatment of AOM, based on their bacteriologic efficacy, cost, taste, ease of administration, and side effects. The author cautions that pneumococci resistant to penicillin may also be resistant to oral cephalosporins and TMP-SMX, so these drugs are best avoided in patients in whom resistance is suspected. 2 figures. 3 tables. 26 references. (AA-M).

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Sensorineural Hearing Loss in Chronic Otitis Media Source: Clinical Otolaryngology and Allied Sciences. 24(3): 220-222. June 1999. Contact: Available from Blackwell Science Ltd. Journal Subscriptions, P.O. Box 88, Oxford, OX2 0NE, United Kingdom. +44 1865 206126. Fax +44 1865 206219. Summary: Although many studies have demonstrated an association between chronic otitis media (COM) and sensorineural hearing loss (SNHL), there still remains disagreement about the relationship. This article reports on a retrospective study that was conducted to examine the relationship between sensorineural hearing loss and chronic otitis media. Forty one patients met the following criteria: unilateral COM and no history of head injury, meningitis or previous otological surgery. The differences in preoperative bone conduction threshold between diseases and control (contralateral normal) ear were statistically significant and varied from 5.24 to 9.02 dB across the

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frequency range. The higher frequencies are more affected than the lower frequencies, but the sensorineural loss is significant across the frequency range. The effect of duration of disease on the degree of SNHL was also analyzed but no correlation was found. The presence of cholesteatoma and or ossicular erosion was not associated with a significantly increased risk of sensorineural hearing loss. 1 figure. 3 tables. 15 references. •

Environmental Tobacco Smoke and Otitis Media Source: Otolaryngology-Head and Neck Surgery. 111(1): 6-8. July 1994. Summary: Although the role of environmental tobacco smoke in the genesis of pulmonary disease in children is recognized, less attention has been paid to the role of environmental tobacco smoke in the development of childhood otitis. This article reviews current data regarding environmental tobacco smoke, with particular emphasis on its effects on the ear and eustachian tube. The author also discusses current American Academy of Otolaryngology-Head and Neck Surgery Foundation educational efforts in this area. 18 references. (AA-M).

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Heritability of Otitis Media: A Twin and Triplet Study Source: JAMA. Journal of the American Medical Association. 282(22): 2125-2130. December 8, 1999. Summary: Anatomical, physiological, and epidemiological data indicate that there may be a significant genetic component to prolonged time with and recurrent episodes of otitis media (middle ear infection) in children. This article reports on a study undertaken to determine the genetic component of time with and episodes of middle ear effusion and acute otitis media (AOM) during the first 2 years of life. The prospective twin and triplet cohort study included enrollment from 1982 through 1995 at the Otitis Media Research Center in the ear, nose and throat clinic of Children's Hospital of Pittsburgh, Pennsylvania. A total of 168 healthy same sex twin and 7 triplet sets were recruited within the first 2 months of life; zygosity results were available for 140 sets. Of these, 138 sets (99 percent) were followed up for 1 year and 126 sets (90 percent) were followed for 2 years. At the 2 year end point, the estimate of heritability of time with middle ear effusion was 0.73. The estimates of discordance for 3 or more episodes of middle ear effusion were 0.04 for monozygotic (identical) twins and 0.37 for dizygotic (fraternal) twins. The estimate of discordance of an episode of AOM in monozygotic twins was 0.04 compared with 0.49 in dizygotic twins. The authors conclude that there is a strong genetic component to the amount of time with middle ear effusion and episodes of middle ear effusion and AOM in children. This finding may influence the primary care physician to identify the siblings and offspring of affected patients as high risk cases. Closer surveillance of patients at risk for middle ear effusion could result in earlier detection and treatment of the disease, as well as prevention of possible developmental problems. 2 figures. 2 tables. 27 references.

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Acute Otitis Media: Part II. Treatment in an Era of Increasing Antibiotic Resistance Source: American Family Physician. 61(8): 2410-2416. April 15, 2000. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: Antibiotic resistance is increasing among the pathogens that commonly cause acute otitis media (AOM, middle ear infection). This article is the second in a series on AOM. The author notes that this increase in antibiotic resistance may require changes in

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the traditional antibiotic treatment of AOM. Risk factors for resistant pathogens include recent antibiotic treatment of AOM, children in day care facilities, wintertime infections, and AOM in children less than 2 years of age. Amoxicillin remains the antibiotic of first choice, although a higher dosage (80 mg per kg per day) may be indicated to ensure eradication of resistant Streptococcus pneumonia. Oral cefuroxime or amoxicillin clavulanate and intramuscular ceftriaxone are suggested second line choices for treatment failure. Compliance with antibiotic regimens is enhanced by selecting agents that require less frequent dosing (such as one or two times a day) and by prescribing shorter (five days or less) treatment courses. Selective use of tympanocentesis if the patient does not respond to empiric therapy can help confirm the diagnosis and guide effective therapy. 2 figures. 2 tables. 30 references. •

Update on Otitis Media in Children Source: Volta Review. 9(5): 97-117. November 1999. Contact: Available from Alexander Graham Bell Association for the Deaf and Hard of Hearing. Subscription Department, 3417 Volta Place, NW, Washington, DC 20007-2778. Voice/TTY (202) 337-5220. Website: www.agbell.org. Also available as individual copies from Publication Sales Department, 3417 Volta Place, NW, Washington, DC 20007-2778. Voice/TTY (202) 337-5220. Website: www.agbell.org. PRICE: $22.95 plus shipping and handling. Summary: Except for viral upper respiratory infections, acute otitis media (middle ear infection) is the most common disease in children. This chapter on otitis media in children is from a monograph that was written by assembling the leading experts from all over the country to present to both the consumer and the professional the latest information on the diagnosis and management of hearing loss in children and adults. The author notes that treatment is often controversial, especially the treatment of persistent otitis media with effusion (OME). The author begins by defining terms used in the chapter, then discusses the health care costs associated with acute otitis media and with OME. The next section considers epidemiology, including genetic predisposition, craniofacial growth abnormalities, infectious load, maternal lifestyle, prone sleeping position, secondary smoke exposure, living in a developing nation, and breast milk. Other topics covered include pathogenesis, diagnosis, microbiology, and treatment options, including antibiotics, steroids, allergy control, autoinflation, mechanical ventilation with or without tube placement, and adenoidectomy. 147 references.

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Hearing Loss and Use of Personal Stereos in Young Adults with Antecedents of Otitis Media (letter) Source: Lancet. 353(9146): 35. January 2, 1999. Summary: In France, young men aged 18 to 24 years undergo systematic medical assessments in the selection centers of the army. This brief research report describes a study in which the authors did a cross sectional study of risk factors for deafness in 1,208 young men from two such selection centers in Vincennes (n = 525) and Lyon (n = 683). The researchers assessed hearing status by tonal automated audiometry. The men were interviewed about hearing status and exposure to potential harmful sources of noise. Additionally, in Lyon, the researchers recorded antecedents of childhood ear diseases, including history of repeated episodes of otitis media. Of the total population, in 449 (38 percent) of 1,194, the hearing threshold was slightly increased in men who went to rock concerts and discos twice a month or more. Hearing thresholds at 2 kHz and 4 kHz were significantly increased in 214 (18 percent) of 1,208 men with noisy

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occupations (for six months or longer). The major factor influencing hearing was use of personal stereos. Hearing thresholds were increased at all frequencies of 1,208 men who used personal stereos for at least 1 hour per day. However, further analysis of the data from the Lyon center showed that this harmful effect was strongly dependent on the presence or absence of repeated episodes of otitis media in infancy or childhood. Personal stereo use had no apparent effect on the hearing status of men without previous otitis media. 1 figure. 5 references. •

The Role of Rhinitis in Chronic Otitis Media Source: Otolaryngology-Head and Neck Surgery. 2003;128:27-31. Contact: Send requests to: Olavo Mion, MD. Otorhinolaryngology Division, University of Sao Paulo Hospital, Av Dr Eneas de Carvalho Aguiar, 255-6 Andar, Sala 6022, Sao Paulo, Brazil. Summary: In this article the authors report on an investigation of the role of allergic rhinitis in chronic otitis media (otitis media with effusion (OME) and chronic perforation of the tympanic membrane) in Sao Paulo, Brazil and whether there is any association between diseases. The study participants included 51 patients divided into 3 groups: allergic rhinitis, nonallergic rhinitis with eosinophils syndrome (NARES), and patients with types of rhinitis or without rhinitis.

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Exploring the Impact of Otitis Media on Hearing and Language Source: Advance for Speech-Language Pathologists and Audiologists. 4(10): 7. May 16, 1994. Contact: Available from Advance for Speech-Language Pathologists and Audiologists. Merion Publications, Inc., 650 Park Avenue West, King of Prussia, PA 19406-4025. (800) 355-1088. Summary: In this article, the author reports on current research activities that are exploring the impact of otitis media on hearing and language. Research projects covered include a study of more than 60 school-age children, followed since they were infants; and the long-term follow-up of children at risk for otitis media. One researcher is quoted as stressing that the areas of higher order language and auditory processing skills are coming to the forefront in research today and need to be investigated closely, even if the child's basic language skills initially seem adequate.

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Otitis Media with Effusion in Infants and Children: Primary Care Concerns Addressed from an Otolaryngologist's Perspective Source: Postgraduate Medicine. 97(1): 137-138,143-144,147,151. January 1995. Summary: In this article, the authors describe acute and chronic otitis media, explain how to diagnose and treat patients in order to avoid lifelong problems, and suggest when to call in an otolaryngologist. The article is organized as a question-and-answer session between a hypothetical primary care physician (Dr. PC) and an otolaryngologist (Dr. OTO). Specific topics covered include terminology used to refer to middle ear disease; the natural history of otitis media; follow-up and determination of long-term prophylactic care; the use of antihistamines or decongestants; the use of systemic steroids; why recurrent otitis media with effusion (OME) is a problem if there are no symptoms; referring a patient for surgical therapy; the problem of early significant hearing loss on a child's development; determining when to obtain a typanogram and an audiogram; the role allergies may play in otitis media with effusion; the role of

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eustachian tube dysfunction; prophylactic antibiotic therapy; and avoidable risk factors for OME in children. 15 references. (AA-M). •

Rise of Acute Otitis Media Source: Patient Care. 29(16): 22-52. October 15, 1995. Summary: In this article, the authors review the diagnosis and treatment of acute otitis media (OM) and otitis media with effusion (OME). The authors stress that the potential complications and sequelae of acute OM and OME represent significant health hazards for children, and include mastoiditis, labyrinthitis, petrositis, facial paralysis, and intracranial complications. Topics covered include the incidence of acute OM; diagnosing acute OM, including the use of a pneumatic otoscope and the role of tympanometry; the bacterial causes of OM; selecting an antibiotic; the growing problem of antibiotic resistance; pain control; determining when myringotomy is needed; followup care; and managing recurrent or persistent OM. A patient care flowchart for managing acute otitis media is presented. 3 figures. 3 tables. 14 references.

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Otitis Media Reassessed: Up-to-Date Answers to Some Basic Questions Source: Postgraduate Medicine. 97(5): 73-82. May 1995. Summary: In this article, the third of four articles on ear, nose, and throat (ENT) problems, the authors reassess the diagnosis and treatment of otitis media in children. Topics covered include a definition and discussion of terminology; the significance of otitis media in U.S. children; etiology; diagnosis; determining who should be treated and why; treating otitis media with effusion (OME); treatment options, for acute otitis media, recurrent otitis media, and OME; determining when to refer to an otolaryngologist for evaluation; and the complications of otitis media. The author concludes that, for children with acute otitis media, appropriate antibiotic therapy provides a modest improvement over the high rate of spontaneous recovery and has greatly reduced the incidence of serious complications. 1 figure. 3 tables. 20 references. (AA-M).

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Five vs. Ten Days of Antibiotic Therapy for Acute Otitis Media in Young Children Source: Pediatric Infectious Disease Journal. 19(5): 458-463. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Many publications in recent years have argued in favor of shortened therapy for acute otitis media (AOM, middle ear infection). However, doubt persists regarding children younger than 2 years, and some authors therefore resist short course therapy to children older than 2 years. This article reports on a study that compared five versus ten days of antibiotic therapy for AOM in young children (cefpodozime proxetil, 8 mg per kg per day). Between October 1996 and April 1997, 450 children (mean age, 14.3 months) were enrolled in the study; 227 children in the 5 day group (followed by a 5 day placebo period) and 223 in the 10 day group. Clinical success was obtained on Days 12 to 14 after the beginning of treatment in 175 (84.1 percent) of the 208 children receiving the 5 day regimen, and in 194 (92.4 percent) of the 210 children receiving the 10 day regimen. The superiority of the standard regimen (10 days) was more marked among children cared for outside their homes (92.5 percent versus 81.5 percent). Clinical success persisted on Days 28 to 42 among 134 (85.4 percent of the 157 assessable patients in the 5 day group, and in 144 (83.7 percent) of the 172 assessable patients in the 10 day group. The authors

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conclude that the 10 day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol. 5 tables. 23 references. •

Clinical Course, Complications and Sequelae of Acute Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S37-S46. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Motivated by the introduction of a new vaccine to prevent pneumococcal infections in infants and children, this article reviews the state of knowledge of the clinical course, complications, and sequelae of acute otitis media (AOM, middle ear infections) caused by this organism (the most common cause of AOM). The author first describes the clinical course of AOM in which the child has been treated with an antimicrobial agent. Thus, the clinical course will not truly be the natural history of the disease. Even though today some clinicians suggest withholding antibiotics or practicing selectivity in prescribing these agents in some or even in all children who have AOM, the current recommendation from official organizations is to prescribe a course of an antimicrobial agent that has been demonstrated to be safe and effective. These recommendations are accompanied by the caution that an acute middle ear infection be diagnosed correctly and distinguished from otitis media with effusion (OME). The usual recommendation is 10 day course of most of the approved oral antibiotics; amoxicillin remains the initial agent of choice. After detailing the clinical course, the author describes the suppurative complications and sequelae of otitis media (OM) that occur within the temporal bone and intracranial cavity. 5 figures. 5 tables. 61 references.

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Review of Consensus Reports on Management of Acute Otitis Media Source: Pediatric Infectious Disease Journal. 18(12): 1152-1155. December 1999. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Much of the current dialog about management of acute otitis media (AOM, middle ear infection) is driven by concern about multidrug resistant strains of Streptococcus pneumoniae and beta lactam producing Haemophilus influenzae. This article offers a review of consensus reports on the management of AOM. Many pediatric infectious disease experts have expressed opinions about the use of antimicrobial agents for AOM, but two publications have been of particular importance and influence in providing guidance. First, an article on otitis media was included in a supplement to Pediatrics (January 1998) entitled 'Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper Respiratory Tract Infections;' and second, a report from the Drug Resistant Streptococcus pneumoniae Therapeutic Working Group of the CDC was published, entitled 'Acute Otitis Media: Management and Surveillance in an Era of Pneumococcal Resistance.' The recommendations provided a guide to management decisions and choice of antimicrobial agents for initial therapy and relapse and recurrence after initial therapy. The two papers represent important responses from national organizations about techniques to limit the increasing incidence of antibiotic resistance among the bacterial pathogens responsible for AOM. This review article considers the questions raised by the recommendations and their current relevance in the management of AOM. 2 tables. 14 references.

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Acute Otitis Media in an Era of Drug Resistance: Implications for NP Practice Source: Nurse Practitioner. 24(10 Supplement): 10-14. October 1999. Contact: Available from Nurse Practitioner. Circulation Department, P.O. Box 5053, Brentwood, TN 37024-5053. (800) 490-6580. Fax (615) 377-0525. Website: www.tnpj.com. Summary: Nearly two thirds of all children will have at least one episode of acute otitis media (AOM) by age 2 years. AOM is the most common indication for pediatric outpatient and antibiotic therapy. Written for nurse practitioners, this article outlines the recommendations for treatment of AOM in an era of drug resistance. The author describes the risk factors for AOM, how to reduce AOM risks, the characteristics of the most common bacterial organisms that cause AOM, the most common causative viruses in AOM, clinical findings in AOM and in recurrent otitis media, clinical features of treatment failure, factors that influence the development of drug resistant pathogens, the role of macrolides (including azithromycin and clarithromycin) in the treatment of AOM, the role of injectable antibiotics in the treatment of AOM, the use of second line therapies in the treatment of AOM, complications that can arise from acute or recurrent otitis media (including otitis media with effusion and hearing loss), the role of decongestants and antihistamines in the treatment of acute and recurrent otitis media, and recommendations for follow up treatment. The author stresses that minimizing AOM risk factors and prescribing the most appropriate and effective AOM therapy, while limiting inappropriate antimicrobial use is an important part of pediatric primary care. 2 tables. 14 references.

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Management of Otitis Media Among Children in a Large Health Insurance Plan Source: Pediatric Infectious Disease Journal. 18(3): 239-244. March 1999. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Otitis media (middle ear infection) is one of the most common office diagnoses among children in the United States and is the leading reason for the use of antimicrobials in pediatric practice. This article reports on a study undertaken to characterize the medical and surgical management of otitis media. Using claims data from a large New England health insurer, the authors identified all children younger than 10 years of age who had one or more episodes of acute otitis media (AOM) between July 1995 and June 1996, and examined patterns of treatment for this condition. Study subjects (n = 22,004) averaged 2.9 physician office visits for the management of otitis media; among children younger than 2 years of age, one fourth had 6 or more such visits. Amoxicillin was prescribed as initial therapy in more than one half (56.6 percent) of all episodes of AOM, followed by cephalosporins (18.3 percent), trimethoprim sulfamethoxazole (12.3 percent), macrolides (6.4 percent), and amoxicillin clavulanate (6.0 percent). Over multiple episodes, however, use of amoxicillin declined by about 50 percent. Antimicrobial prophylaxis was received by 7.3 percent of all study subjects for a mean of 61.3 days; the incidence of breakthrough episodes of AOM during prophylaxis varied according to the antimicrobial used. Surgical procedures related to otitis media were performed on 3.8 percent of all study subjects, including 4.6 percent of children younger than 2 years of age. The authors conclude that the health care burden of otitis media is large, particularly in the first 2 years of life. 8 tables. 13 references.

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Otitis Media: Back to Basics Source: Pediatric Infectious Disease Journal. 17(12): 1105-1113. December 1998.

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Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Otitis media is the most common disease diagnosed during childhood, accounting for 20 to 40 percent of office visits in the first 5 years. Otitis media is also the primary reason for the dispensing of antibiotics in the United States and as a result contributes substantially to the development of antibiotic resistance. This continuing education article reviews the basics of diagnosing and caring for patients with otitis media (middle ear infection, OM). The authors differentiate acute otitis media (AOM) from otitis media with effusion (OME); describe the expected frequency and duration of OM episodes as well as the total time spent with middle ear disease; discuss the use of the term 'otitis prone,' and discuss factors that lead to the development and recurrence of OM. AOM is symptomatic and should be treated with antibiotics. OME is asymptomatic and need not be treated with antibiotics unless it persists beyond 3 months. In an effort to reduce the frequency of OM, physicians should encourage breastfeeding, discourage maternal smoking, discourage pacifier usage in the older infant, and recommend smaller day care programs whenever possible. Appended to the article are review questions for readers to self test their knowledge. 4 figures. 6 tables. 83 references. •

Evidence of Bacterial Metabolic Activity in Culture-Negative Otitis Media with Effusion Source: JAMA. Journal of the American Medical Association. 279(4): 296-299. January 28, 1998. Summary: Otitis media with effusion (OME) can lead to significant hearing loss in children. Although previous studies have shown that bacterial DNA is present in a significant percentage of effusions determined sterile by culturing, whether the DNA represents viable organisms (bacteria) or fossilized remains is unknown. This article reports on a study undertaken to determine if bacterial messenger RNA (mRNA) is present in chronic pediatric middle ear effusions that contain bacterial DNA but are considered sterile by standard cultural methods. Bacterial mRNAs have a half-life measured in seconds to minutes; therefore, detection of bacteria-specific mRNAs would be evidence that metabolically active organisms are present. A total of 93 effusions from pediatric outpatients seen for myringotomy and tube placement for chronic OME were studied. Eleven (11.8 percent) of the 93 specimens tested positive by culture, PCR (polymerase chain reaction) and RT-PCR (reverse transcriptase, polymerase chain reaction), for Haemophilus influenzae. A total of 29 specimens (31.2 percent) were positive by PCR but negative by culture for H influenzae; all 29 of these specimens were positive for H. influenzae-specific mRNA (tested by RT-PCR). The authors conclude that the RT-PCR based system can detect the presence of bacterial mRNA in a significant percentage of culturally sterile middle ear effusions, establishing the presence of viable, metabolically active, intact organisms in some culture-negative OME. 1 figure. 2 tables. 19 references. (AA-M).

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Relationship Between Otitis Media with Effusion and Allergy Source: Current Opinion in Otolaryngology. 5(1): 46-48. February 1997. Summary: Otitis media with effusion (OME) is one of the leading causes of acquired hearing loss in children. The role of allergy in various disorders of the respiratory tract is well known. However, the relationship between allergy and the pathogenesis of OME is still under investigation. This article reviews and summarizes recent research in this

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area. Studies with favorable as well as unfavorable results regarding an allergic etiology continue to provide information about the multifactorial nature of the disease process. The authors review epidemiology studies, studies on pathophysiology, and clinical studies and case reports. The authors conclude that an important consideration in the treatment of OME is to recognize its multifactorial etiology (many causes). In addition to the immature immune response seen in young children, viral infection, allergy, and imbalance of the normal nasopharyngeal flora all appear to contribute to the progression of OME. Certainly, all children with OME do not necessarily have an allergic cause. However, there appears to be a sizable subgroup of children with OME in whom allergy may play a role. 18 references (5 annotated). (AA-M). •

What Role for Antibiotics in Otitis Media and Sinusitis? Source: Postgraduate Medicine. 104(3): 93-99, 103-104. September 1998. Contact: Available from Postgraduate Medicine. P.O. Box 459, Hightstown, NJ 085209201. (609) 426-7070. Fax (609) 426-7087. Summary: Patients often expect to be given antibiotics for any illness affecting the ears and sinuses, regardless of whether such treatment is warranted. This article, the fourth of four articles on common ear, nose, and throat (ENT) problems, discusses the role for antibiotics in treating otitis media (middle ear infection) and sinusitis (sinus infection). The authors caution that bacterial resistance to antibiotics is rising. They outline the types of otitis media and sinusitis that should be treatment with antibiotics and the agents that are currently the most effective for each condition. The authors review the established classification and treatment guidelines for these conditions. First-line treatment for both uncomplicated acute otitis media and acute sinusitis is amoxicillin. Erythromycin ethylsuccinate and sulfisoxazole or TMP-SMZ may be used in patients who are allergic to penicillin. Beta-lactamase-stable agents should be given when no response occurs within 48 to 72 hours. In cases where penicillin-resistant pneumococcus is suspected, high-dose amoxicillin, with or without clavulanate, or clindamycin should be considered. Antibiotics are not indicated for initial treatment of otitis media with effusion (OME), but may be considered for effusions lasting longer than 3 months. Prophylactic antibiotics should be considered only for recurrent acute infections occurring three or more times within 6 months or four or more times with a year. 4 tables. 27 references. (AA-M).

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Potential of Bacterial Vaccines in the Prevention of Acute Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S72-S78. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Patients with acute otitis media (AOM, middle ear infection) compose a large part of the daily practice of most general practitioners and pediatricians. Prevention of even a small portion of the AOM cases would have a major impact from both the public health and economics point of view. In this article, the published data on the role of the three most significant causative agents of AOM are reviewed; these agents are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Although other bacteria may also cause AOM (e.g., Streptococcus pyogenes, Staphylococcus aureus, and several Gram negative bacteria), they are not discussed in this article. This is in part because of their minor and somewhat controversial role as true pathogens in AOM, but mostly because the development of vaccines has not progressed to the point where one might consider them viable candidates. The authors

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present recent data from two Finnish prospective studies to illustrate the potential impact of pneumococcal conjugate vaccines in the prevention of AOM. In addition, the authors review the development of other new vaccines based on antigens from S. pneumoniae, H. influenzae, and M. catarrhalis. These vaccines are still in the preclinical phase of development, so their eventual impact on AOM remains speculative. 4 tables. 83 references. •

Otitis Media and Child Development: Should We Worry? Source: Pediatric Infectious Disease Journal. 17(11): 1076-1083. November 1998. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Persistent middle ear effusion in infancy and early childhood has been blamed for impairments of speech, language, cognition, and psychosocial development later in life. Whether that blame is justified remains unresolved and a matter of controversy, because studies of the relationships involved have been limited and often contradictory and because none was designed so as to address the issue of causality. At issue in particular is the common practice of subjecting infants and young children with persistent otitis media with effusion (OME) to tympanostomy (ventilation) tube placement specifically to reduce the risk of developmental impairment. Currently children younger than age 3 years undergo an estimated 313,000 tympanostomy tube placement operations per year, at a cost of about $750 million. If a causal association between early life OME and later developmental impairment were to be established, answers would also be needed to the questions whether the adverse effects of OME are linear or threshold, whether they are permanent or transient and whether they are preventable by timely tube placement. A prospective study designed to address all of these questions is currently under way at Children's Hospital of Pittsburgh. The study involves enrolling a large, demographically diverse sample of normal infants before 2 months of age; monitoring them for the presence of absence of otitis media through the first 3 years of life; identifying those in whom OME has persisted for specified minimum periods; randomly assigning those subjects either to prompt tube placement or to delayed tube placement if OME persists; and administering a battery of standardized developmental tests to those subjects and to a sample of the others at ages 3, 4, and 6 years. This reports describes details of the study design and procedures. 108 references.

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Randomized Controlled Trial of Point-of-Care Evidence to Improve the Antibiotic Prescribing Practices for Otitis Media in Children Source: Pediatrics. 107(2): [e15]. February 2001. Contact: Available from American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (888) 227-1773. Fax (847) 434-8000. E-mail: [email protected]. Website: www.pediatrics.org. Full text of this article is available at www.pediatrics.org/cgi/content/full/107/2/e15. Summary: Prescribing practices for otitis media (middle ear infection) are not consistent with current evidence based recommendations. So contend the authors of this research study that was undertaken to determine whether point of care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written. The study used a point of care message system (a computer prescription writer software program) as the intervention. Intervention providers had a 34 percent greater reduction in the proportion of time they prescribed antibiotics for less than 10 days. Intervention

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providers were less likely to prescribe antibiotics than were control providers. The authors conclude that the point of care information system integrated into pediatric outpatient care can significantly influence provider behavior for a common condition. 1 figure. 2 tables. 21 references. •

Otitis Media: A Primer on Diagnosis and Management Source: The Hearing Journal. 2003;56;6:42-7. Contact: Hearing Journal. E-mail: [email protected]. Summary: The authors of this article seek to review the definition, pathogenesis, and diagnostic and management options of otitis media (OM). The authors describe OM as one of the most common conditions diagnosed by pediatricians in the United States among and its incidence among children is growing.

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Otitis Media in Children: Diagnosis, Treatment, and Prevention Source: Postgraduate Medicine. 107(3): 239-241, 245-247. March 2000. Summary: The diagnosis and treatment of middle ear infections (otitis media) and effusions continues to be a large part of daily practice for physicians who treat infants and children. This guideline article offers an opportunity for readers to review and compare approaches to this routine problem and to consider some of the details that are easily overlooked in the daily rush between examination rooms. The author begins with appropriate identification of symptoms, then delineates the criteria that differentiate acute otitis media (AOM) from otitis media with effusion (OME). The author then outlines the management strategies to be used with each type. The guideline also mentions important ways to stem the tide of middle ear infections each winter, such as preventing the spread of viral upper respiratory tract infections, avoiding smoke exposure, and encouraging mothers to breastfeed. The author stresses that overtreating and undertreating are equally dangerous pitfalls and do a disservice to pediatric patients and their families. 1 figure.

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Cochlear Implant in the Child Under Two Years of Age: Skull Growth, Otitis Media, and Selection Source: Otolaryngology-Head and Neck Surgery. 117(3, Part 1): 217-219. September 1997. Summary: The goal of cochlear implantation in young children is to provide audition (hearing) adequate to allow for the development of receptive and expressive language. This article considers the indications for cochlear implantation in children under the age of two years, the current lower age limit set by the Food and Drug Administration. The author contends that this limit may deny children critical auditory information during a period when the central nervous system is maximally responsive to stimulation. Factors to consider in implanting before the age of two years include anatomic considerations, temporal bone growth and device extrusion or migration, the sequelae of otitis media, and the accuracy of early diagnosis. The author concludes that clinical experience and laboratory data indicate that technically, cochlear implantation before age two years is an achievable goal. 8 references. (AA-M).

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Clinical Epidemiology of Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S31-S36. May 2000.

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Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: The impact of otitis media (OM, middle ear infection) on public health is considerable. This article explores the clinical epidemiology of OM. OM, with its peak incidence in the first 2 years of life, is the most commonly diagnosed pediatric disease. Between 1993 and 1995, OM was the most common diagnosis during office visits among 1 to 4 year olds. OM constituted 18 percent of physician visits, compared with 14 percent of visits for well child care, 11 percent of visits for upper respiratory infection, 8 percent of visits for injury, and 5 percent of visits for sore throat and tonsillitis. Thirty percent of children younger than 24 months in a large managed care organization were treated with tympanostomy (ventilation) tubes in 1994, and cost of OM treatment in the United States was estimated at $3.8 billion in 1995. Additionally, OM was one of the most common reasons for postponing vaccination for diphtheria, tetanus, pertussis, polio, measles, mumps, and rubella; postponement of the vaccine increases a child's risk for these preventable diseases. The authors conclude that identified host characteristics are useful in targeting high risk children, and well defined environmental factors present potential avenues of primary prevention. Vaccines currently being field tested offer promise for primary prevention, and strategies for risk factor reduction should be tested and implemented. 33 references. •

Nonimmune Strategies for Prevention of Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S89-S92. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: The strategies for the prevention of otitis media (OM, middle ear infection) include parent education, immunoprophylaxis, chemoprophylaxis, surgery, and the use of innovative materials such as oligosaccharides and xylitol. This article reviews the available data, benefits and limitations of each of the nonimmune techniques available for prevention. In contrast to immunoprophylaxis, which protects against disease due to specific pathogens, the nonimmune strategies for prevention are generic and may have broad impact on the incidence of middle ear infections. Risk factors include age (infants are more prone to ear disease), family history, not breastfeeding, day care exposure, and smoking in the home. Prevention strategies include modifying risk factors where possible, the use of antimicrobial agents for decreasing the rate of colonization or intensity of bacterial pathogens, surgery (placement of ventilation tubes), the use of oligosaccharides, and the use of xylitol. The author stresses that all modes of prevention should be included in a strategy for the child who has severe and recurrent infections and who is 'otitis prone' because of known or unknown anatomic, physiologic, or immunologic deficits. 2 tables. 23 references.

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Hearing Loss and Otitis Media in Velo-Cardio-Facial Syndrome Source: International Journal of Pediatric Otorhinolaryngology. 47(3): 227-233. March 15, 1999. Contact: Available from Elsevier Science. P.O. Box 945, New York, NY 10159-0945. (888) 437-4636. Fax (212) 633-3680. E-mail: [email protected]. Summary: There is an increased prevalence of otitis media (middle ear infection) and associated hearing loss in patients with isolated cleft or submucous cleft palates, palatal abnormalities which are well known components of velocardiofacial syndrome (VCFS).

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This article reports on a study of 166 VCFS patients whose records were reviewed for the purpose of documenting the prevalence of middle ear disease and associated conductive hearing loss in this population. Patients were divided according to age, type of palatal abnormality, and presence or absence of chromosomal deletion (using fluorescence hybridization test). Results indicated that the prevalence of middle ear disease in patients with VCFS was 47 percent and the prevalence of hearing loss was 44 percent. The majority of hearing loss was conductive and due to middle ear disease (74 percent); 11 percent of the hearing loss was sensorineural. There was no statistical difference between groups with regard to age, type of palatal abnormality, and presence of chromosomal deletion. The authors conclude that the prevalence of conductive hearing loss secondary to middle ear disease in VCFS is comparable to the prevalence found in isolated cases of cleft palate. Consequently, when caring for patients with VCFS, the need for auditory (hearing) assessment and otological evaluation must be emphasized. 14 tables. 32 references. •

Cost-Effectiveness Considerations in Otitis Media Treatment Source: Otolaryngology-Head and Neck Surgery. 114(4): 525-530. April 1996. Summary: This article considers the elements of cost-effectiveness analysis as they pertain to treatment of young children with otitis media with effusion (OME) and develops a first approximation model using data from several sources. The author stresses that the assumptions on which this model is based need to be validated by additional research. OME costs are high because of the large, and apparently increasing, number of symptomatic cases. Medical therapy, which is the primary treatment modality, consumes two thirds of the expenditures for OME. Surgical therapy is a costeffective treatment for children in whom medical therapy for OME fails. The author concludes that medical and surgical therapy are complementary, and each should be included in the analysis of cost-effectiveness. 2 tables. 16 references. (AA-M).

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Routine Antibiotics: Are They Really Needed for Acute Otitis Media? Source: JAAPA. Journal of the American Academy of Physician Assistants. 11(10): 41-42, 45. October 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645-1742. (800) 432-4570. Summary: This article considers the use of routine antibiotics in the treatment of acute otitis media (ear infection). The author states that otitis media is overdiagnosed and overtreated, and explains his reasons for this conclusion. The author discusses antibiotic use in the U.S. compared to that in Europe, the fear of complications of otitis media (such as meningitis, mastoiditis, and hearing loss), the role of worry over malpractice action, otitis media that is virus induced (for which antibiotics will not be effective), growing worldwide bacterial resistance to antibiotics, the effective management of parents whose children have ear infections, and the shifting to more conservative management of acute otitis media by restricting initial use of antimicrobials. One sidebar offers ten recommendations for the better management of acute otitis media (AOM), including the use of antibiotics but in a more conservative fashion. 10 references.

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Otitis Media and Speech-Language Sequelae in Young Children: Current Issues in Management Source: American Journal of Speech-Language Pathology. 4(1): 15-24. February 1995.

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Summary: This article describes the implications of otitis media with effusion (OME) for the clinical practice of speech-language pathologists. The authors briefly discuss the current literature on the epidemiology of OME and the relationship of OME to language development and later academic performance. They then present strategies for assessment and program planning. The tasks of the speech-language pathologist are discussed, including monitoring for hearing loss and early evidence of developmental delays; sharing information with caregivers about possible developmental sequelae of OME; working with caregivers to provide an optimal health and learning environment; consulting in the medical management of OME; and developing intervention programs. 78 references. (AA-M). •

Clinical Significance of Resistant Organisms in Otitis Media Source: Pediatric Infectious Disease Journal. 19(4): 378-382. April 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: This article explores the clinical significance of resistant organisms in otitis media (middle ear infection). The bacteriology of otitis media comprises three main pathogens: Streptococcus pneumoniae, nontypable Haemophilus influenzae, and Moraxella catarrhalis. Although the prevalence of resistant strains varies geographically and temporally, antimicrobial resistance is widespread and increasing. Among the risk factors for development of resistance in otitis media are antimicrobial use, young age, day care attendance, and prior hospitalization. The increasing rate of resistance to antibiotic drugs is associated with a decreased rate of successful eradication of pathogens from middle ear fluid, which is associated with clinical failure. A bacteriologic cure rate of 80 to 85 percent is observed for S. pneumoniae and nontypable H. influenzae when serum concentrations exceed the MIC for 40 to 50 percent of dosing interval. Comparative trials indicate that some of the beta lactams can achieve bacteriologic eradication in acute otitis media, although major differences in outcome exist among agents based on pathogen, beta lactamase status, and MIC values. The author concludes that overall the choice of antibiotics for treatment of otitis media should take into consideration their in vitro activity against the locally prevalent organisms, especially resistant organisms, and results obtained from studies in which bacteriologic outcome was used as the endpoint. 2 figures. 28 references.

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Acute Otitis Media: Making an Accurate Diagnosis Source: American Family Physician. 53(4): 1200-1206. March 1996. Summary: This article explores the procedure for making an accurate diagnosis of acute otitis media. An otoscope with a fresh bulb and a good power source, as well as a view of the tympanic membrane that is not obstructed by cerumen, are essential to making the diagnosis of acute otitis media. A bulging, cloudy, immobile tympanic membrane is highly associated with otitis media. Erythema of the eardrum alone, however, is often the result of viral infection, crying, or attempts to remove cerumen and should not be the sole basis for the diagnosis of acute otitis media. The authors stress that to avoid the common problem of overdiagnosing acute otitis media, the clinician should consider the predictive values of the various symptoms and physical examination findings associated with ear infections. 4 tables. 26 references. (AA-M).

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Auditory Consequences of Otitis Media with Effusion: the Audiogram and Beyond Source: Seminars in Hearing. 16(1): 44-59. February 1995.

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Summary: This article focuses on the auditory consequences of otitis media with effusion (OME). The article is from an issue of Seminars in Hearing that focuses on the recent empirical and clinical work on the effects of otitis media on psychoacoustic, behavioral, and physiologic factors. The authors describe the consequences of OME that are related to peripheral hearing sensitivity and those that involve higher order auditory processing abilities. They examine the theories of how OME might affect developmental outcome. They also discuss current empiric evidence that suggests auditory-based sequelae are observed in children with early positive middle-ear histories, concentrating on studies that documented middle-ear courses prospectively or through review of comprehensive medical records. The article includes references and self-assessment questions to be used to qualify for continuing education credits. 3 figures. 59 references. •

Auditory Brainstem Response in Children with Histories of Otitis Media Source: Seminars in Hearing. 16(1): 37-43. February 1995. Summary: This article on the auditory brainstem response (ABR) in children with histories of otitis media with effusion (OME) is from an issue of Seminars in Hearing that focuses on the recent empirical and clinical work on the effects of otitis media on psychoacoustic, behavioral, and physiologic factors. The authors discuss relevant animal studies and clinical research investigating the relationship between OME and ABR changes in children. The authors find that children with histories of protracted infant OME continue to have altered ABRs from early childhood into preadolescence. The article includes references and self-assessment questions to be used to qualify for continuing education credits. 4 figures. 27 references.

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Diagnosis and Treatment for Otitis Media Source: Seminars in Hearing. 16(1): 20-27. February 1995. Summary: This article on the diagnosis and treatment of otitis media is from an issue of Seminars in Hearing that focuses on the recent empirical and clinical work on the effects of otitis media on psychoacoustic, behavioral, and physiologic factors. The author focuses on the two most common classifications encountered in clinical practice: acute (bacterial) otitis media and otitis media with effusion (OME). Specific topics covered include diagnostic testing; antibiotics; the use of antihistamines and decongestants; the use of steroids in OME; insufflation of the middle ear; and surgical options for treatment. The author stresses that a team approach, with participation of an otolaryngologist and an audiologist, is important in order to derive a final diagnosis. The article includes references and self-assessment questions to be used to qualify for continuing education credits. 23 references.

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Factors Disposing for Otitis Media Source: Seminars in Hearing. 16(1): 1-19. February 1995. Summary: This article on the factors disposing for otitis media is from an issue of Seminars in Hearing that focuses on the recent empirical and clinical work on the effects of otitis media on psychoacoustic, behavioral, and physiologic factors. The author highlights the etiology, course, and prevalence of otitis media with a focus on acute purulent otitis media (AOM). The emphasis in on those with recurrent episodes and secretory otitis media (SOM) or otitis media with effusion (OME). Specific topics covered include selected congenital and hereditary factors; the nasopharyngeal presence of bacteria; social factors; the role and type of child care; breast feeding and passive smoking; and identifying children at risk. The article includes references, a glossary, and

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self-assessment questions to be used to qualify for continuing education credits. 8 figures. 92 references. •

Immunologic Evaluation of the Child with Recurrent Otitis Media Source: ENT. Ear, Nose, and Throat Journal. 76(1): 31-42. January 1997. Summary: This article outlines the immunologic evaluation of the child with recurrent otitis media (middle ear infection). After a brief review of the pathogenesis of acute otitis media, the author addresses the role of the immune system in host defenses against otitis media, the significance of recurrent otitis media as a symptom of immune deficiency, the considerations for referring a child with recurrent otitis media for immune deficiency evaluation, and the components of such an immunology evaluation. The author concludes that the immunologic evaluation of the otherwise healthy child with recurrent otitis media is simple, cost-effective, and often comforting for both parents and physician. In any child suspected of having an immune deficiency, certain precautions are warranted. Exposure to highly infectious environments, such as daycare centers, should be limited until the immune status of the child is clarified. Live virus vaccines should be avoided. Any blood product which might be required by a child with a suspected immune deficiency should be irradiated to prevent the transmission of viable immunologic cells and the generation of graft versus host disease. 3 figures. 4 tables. 21 references.

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Otitis Media with Effusion in Young Children: Guideline Overview Source: Journal of the National Medical Association. 86(10): 731-732, 792-793. Summary: This article provides an overview of the Public Health Service clinical practice guideline on the diagnosis, treatment, and management of otitis media with effusion (OME) in young children. A multidisciplinary panel of private sector experts was convened to assist the contractor in developing the guideline. The panel's recommendations fall into two broad areas: the diagnosis of OME and evaluation of hearing and management of OME. In addition, the panel discussed several other issues of interest, including the relationship of OME to allergy and certain environmental factors, such as cigarette smoke. The target patient for the panel's recommendations is an otherwise healthy child, age 1 through 3 years, who has no craniofacial or neurologic abnormalities or sensory deficits. The article concludes with a description of the three forms in which readers can obtain the guideline: Clinical Practice Guideline; Quick Reference Guide; and Parent Guide.

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Treatment of Acute Otitis Media with a Shortened Course of Antibiotics: A MetaAnalysis Source: JAMA. Journal of the American Medical Association. 279(21): 1736-1742. June 3, 1998. Summary: This article reports on a meta analysis of randomized controlled trials of antibiotic treatment of acute otitis media (AOM) in children; the analysis was undertaken to determine whether outcomes were comparable in children treated with antibiotics for less than 7 days or at least 7 days or more. The authors conducted MEDLINE, EMBASE, Current Contents, and Science Citation Index searches to identify randomized controlled trials of the treatment of AOM in children with antibiotics of different durations. Trial methodological quality was assessed independently by 7 reviewers; outcomes were extracted as the number of treatment failures, relapses, or reinfections. The summary odds ratio for treatment outcomes (measured at 8 to 19 days

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posttreatment) in children treated with short acting antibiotics for 5 days versus those treated for 8 to 10 days was 1.52; however, by 20 to 30 days posttreatment, the outcomes between treatment groups were comparable. The authors conclude that 5 days of short acting antibiotic use is effective treatment for uncomplicated AOM in children. 2 figures. 2 tables. 88 references. •

Risk Factors of Otitis Media with Effusion During Infancy Source: International Journal of Pediatric Otorhinolaryngology. 48(3): 239-249. May 25, 1999. Contact: Available from Elsevier Science. P.O. Box 945, New York, NY 10159-0945. (888) 437-4636. Fax (212) 633-3680. E-mail: [email protected]. Summary: This article reports on a study in which possible risk factors were associated with the prevalence of otitis media (middle ear infection) with effusion (OME) in a group of 250 infants (aged 0 to 2 years). In order to determine OME, otoscopy and tympanometry were performed at 3 monthly intervals beginning at term date (date when the baby was expected to be born). Eighteen epidemiology features were inventoried by the use of a questionnaire. The prevalence of OME was most strongly associated with age. Other factors significantly associated with the prevalence of OME were gestational age, birth weight, breastfeeding, day care attendance, number of siblings, season, and parent reported ear infection, hearing loss, mouth breathing, and common cold. No significance was found for gender, date of birth, passive smoking, family history of otitis media, parental socioeconomic status, and histories of snoring and consultation of a physician. The authors conclude that both intrinsic and extrinsic factors appear to play an important role in the prevalence of OME. Some of the risk factors may be age dependent (birth weight and prematurity) and others appeared to be time dependent (breastfeeding, day care attendance, and season). 30

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Early Childhood Otitis Media in Relation to Children's Attention-Related Behavior in the First Six Years of Life Source: Pediatrics. 107(5): 1037-1042. May 2001. Contact: Available from American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. Website: www.pediatrics.org. Summary: This article reports on a study that examined whether otitis media with effusion (OME, middle ear infection) and associated hearing loss during the first 4 years of life were related to the ratings of parents, teachers, and clinicians of children's attention and behavior in the first 6 years of life. In this prospective study, 85 children were recruited from community based child care programs when they were between 6 and 12 months old. OME and hearing status were monitored repeatedly from 6 months to 4 years old. Measures of attention and behavior were collected from parents, teachers, and clinicians when the children were infants, preschoolers, and first graders. On average, children experienced either bilateral or unilateral OME 30 percent of the time and hearing loss 19.9 percent of the time between 6 months and 4 years old. Descriptive and inferential analyses revealed no significant associations between OME or hearing loss and the measures of attention or behavior. The authors conclude that, in this sample of children, there was no relationship between amount of early childhood OME or hearing loss and measures of attention or behavior in the first 6 years of life as reported by parents, teachers, and clinicians. 2 tables. 41 references.

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Practice Patterns Versus Practice Guidelines in Pediatric Otitis Media Source: Otolaryngology-Head and Neck Surgery. 124(5): 489-495. May 2001. Contact: Available from Harcourt Health Sciences, Subscription Customer Service, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Fax (407) 363-9661. Website: www.harcourthealth.com. Summary: This article reports on a study undertaken to investigate the practice patterns of physicians and their adherence to an evidence based practice guideline (PG) on pediatric otitis media with effusion (OME, middle ear infection). The authors hypothesized that overall knowledge of the recommendations from the guidelines would be less than 75 percent, and that specialist physicians would have better knowledge of the recommendations than generalist physicians. The survey study included 1,167 otolaryngologists, pediatricians, and pediatric otolaryngologists. Each physician was sent a 6 item survey asking about their practice patterns and treatment preferences for young children with OME. The overall response rate was 48 percent. Only 8 (1.4 percent) of the 558 responding physicians answered all 6 items congruent with the PG. Overall, pediatricians, otolaryngologists, and pediatric otolaryngologists had similar total scores, but different scores on individual items. The authors were particularly concerned by the results on 2 items covering key treatment recommendations which were answered in agreement with the PG by fewer than half of the physicians. It is not clear from this study whether these discrepancies were due to poor dissemination or knowledge of the PG, or disagreement with its recommendations. 2 tables. 22 references.

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Hearing Aids Versus Ventilation Tubes in Persistent Otitis Media with Effusion: A Survey of Clinical Practice Source: Journal of Laryngology and Otology. 115(4): 274-279. April 2001. Contact: Available from Royal Society of Medicine Press Limited. Publications Subscription Department, P.O. Box 9002, London W1A 0ZA, United Kingdom. E-mail: [email protected]. Summary: This article reports on a survey that was carried out to determine the current clinical practice amongst consultant otolaryngologists (ear, nose, and throat specialists) in the United Kingdom, regarding reinsertion of ventilation tubes or recommendation of hearing aids in cases of recurrence of otitis media with effusion (OME, middle ear with fluid drainage) after ventilation tube extrusion. Among the 319 respondents, 15 (4.70 percent) routinely, 146 (45.77 percent) sometimes, and 158 (49.43 percent) either never, or very rarely, recommend hearing aids. Hearing aids and ventilation tubes were both suggested to be equally good options by some consultants but they preferred surgery for a number of reasons. There were inconsistencies in practice and some of the reasons for reinserting ventilation tubes are not evidence based. The authors conclude that a hearing aid is a noninvasive option and this survey shows a need for a randomized control trial of hearing aids and ventilation tubes in the management of persistent and recurrent OME. The survey instrument is appended to the article. 6 tables. 12 references.

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Studies Probe Medical Intervention for Otitis Media Source: Advance for Speech-Language Pathologists and Audiologists. 4(32): 5. December 12, 1994. Contact: Available from Merion Publications, Inc. 650 Park Avenue West, King of Prussia, PA 19406. (800) 355-1088.

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Summary: This article reports on current research in the area of medical intervention for otitis media. After a description of the incidence of otitis media and the prevalence of surgery to treat the problem, the author describes studies undertaken to test the efficacy of alternative treatments. One of the research studies focused on a population of pediatric patients with allergies, highlighting the researcher's belief that allergies frequently cause ear effusion. Another study investigated the efficacy of a combined treatment of an antihistamine with a decongestant. The last study discussed demonstrated that a combined treatment of antibiotics and intranasal corticosteroids also may be effective in treating children with middle ear infection. •

Chronic Otitis Media With Effusion in Infancy: How Frequent Is It? How Does It Develop? Source: Archives of Otolaryngology-Head and Neck Surgery. 121(4): 432-436. April 1995. Summary: This article reports on research undertaken to study the occurrence and development of chronic otitis media with effusion (OME) in infancy. Information was gathered on a random sample of 2512 children from a birth cohort with a 2-year followup. Chronic OME was determined as a minimum of 2 months of asymptomatic middle ear effusion revealed by tympanocentesis and specific operative findings. Results showed that the periodic prevalence rate of chronic OME up to the age of 24 months was 4.4 percent. The maximum risk was at age 16 months. The number of acute otitis media episodes among children who developed chronic OME was more than double that of normal healthy children before the onset of chronic inflammation and about five times as high during prolong mucous middle ear effusion. 1 figure. 3 tables. 32 references. (AA-M).

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Eustachian Tube Function and Otitis Media in Children Source: ENT. Ear, Nose and Throat Journal. 77(9): 762, 764, 766, 768-769. September 1998. Contact: Available from MEDQUEST Communications LLC. 629 Euclid Avenue, Suite 1200, Cleveland, OH 44114. (216) 522-9700. E-mail: [email protected]. Summary: This article reviews eustachian tube function and the factors that are responsible for the development and maintenance of otitis media (middle ear infection) in children. The opening and closing function of the eustachian tube is of decisive importance to hearing. The closed tube protects the ear from sounds from the respiratory tract and oral cavity, whereas the opening of the tube makes it possible to equalize the pressure gradient over the eardrum, which is necessary for the optimal function of the middle ear. Recent findings from studies of populations of children with and without otitis media show that a poor ability to equalize negative pressure is a fundamental deficit of eustachian tube function. Not only was active function found to be poor in children with otitis media with effusion, it was also impaired in healthy children, as compared to adults. However, the deficit improved with age and time. The authors note that active rather than passive tubal function seems to be of critical importance when considering the risks for recurrent acute otitis media and secretory otitis media (or otitis media with effusion, OME). This suggests the involvement of primarily a eustachian tube opening dysfunction or muscular opening hypofunction in children. In addition, in a subgroup of children with recurrent acute otitis media or secretory otitis media, habitual sniffing in combination with closing failure and poor

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active function may be a possible mechanism for the development of otitis media. 2 tables. 24 references. (AA-M). •

Recent Advances in the Treatment of Otitis Media Source: Journal of Clinical Pharmacy and Therapeutics. 17(4): 201-215. February 1992. Summary: This article reviews recent advances in the treatment and prevention of otitis media (OM) in infants and children. Topics covered include pathophysiology and bacteriology; recent studies of antibiotics; duration of antimicrobial therapy; adjunctive and investigational therapies, including corticosteroids, topical antibiotics, and implantable antibiotic-impregnated film; and the use of immune globulin, vaccinations, and prophylactic antibiotics in the prevention of otitis media. 2 tables. 82 references.

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Medical and Audiological Management of Otitis Media: Consensus and Controversy Source: Seminars in Hearing. 16(1): 105-112. February 1995. Summary: This article reviews the areas of consensus and the areas of controversy in the medical and audiological management of otitis media. The article is from an issue of Seminars in Hearing that focuses on the recent empirical and clinical work on the effects of otitis media on psychoacoustic, behavioral, and physiologic factors. Topics covered include the identification of otitis media with effusion (OME); the medical management of otitis media; the effects of OME on hearing and higher order auditory function; and screening for OME. The authors conclude that in all likelihood, intrinsic and extrinsic variables unique to each child combine with OME in determining the developmental consequences of this disease. 1 reference.

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Otitis Media and Disordered Phonologies: Some Concerns and Cautions Source: Topics in Language Disorders. 14(2): 72-83. February 1994. Summary: This article reviews the association between otitis media with effusion and phonological impairment. The author notes that many questions have gone unanswered, such as why large numbers of children who experience early persistent otitis media do not present phonological deficits, and what specific measures might facilitate therapy for those who do. The author first reviews problems faced by researchers and then summarizes established findings concerning otitis media and its effects on phonological acquisition. Professionals are warned neither to ignore nor exaggerate the possible influence of a history of otitis media on a child's phonological deficits. 20 references. (AA-M).

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Otitis Media in Children: Frequency, Risk Factors, and Research Avenues Source: Epidemiologic Reviews. 15(2): 444-465. 1993. Summary: This article reviews the epidemiology of otitis media in children. Topics covered include definitions and terminology; the incidence, prevalence, and natural course of acute otitis media and otitis media with perfusion; host factors, including age and sex, race, anatomy, eustachian tube function, allergy, immunity, and infection; risk factors, including season, indoor environment, socioeconomic status, breast-feeding, type of day care, and passive smoking; and methodological issues, including definition of the disease, the validity of diagnostic procedures, and study design. The authors stress that clarifying the specific characteristics of hearing loss during childhood, particularly its long-term developmental and behavioral consequences, is of capital

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importance. They conclude by calling for additional studies to improve the knowledge of the causal and prognostic factors of otitis media. 5 tables. 74 references. •

Acute Otitis Media: Management and Surveillance in an Era of Pneumococcal Resistance-A Report from the Drug-Resistant Streptococcus Pneumoniae Therapeutic Working Group Source: Pediatric Infectious Disease Journal. 18(1): 1-9. January 1999. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 350, Hagerstown, MD 21740-0350. Website: www.lww.com. Summary: This article summarizes the report of a therapeutic working group that was convened to provide consensus recommendations for the management of acute otitis media (AOM) and the surveillance of drug resistant Streptococcus pneumoniae (DRSP). Five areas were addressed, considering published and unpublished data from the scientific literature and from the experts present. Oral amoxicillin should remain the first line antimicrobial agent for treating AOM. In view of the increasing prevalence of DRSP, the safety of amoxicillin at higher than standard dosages and evidence that higher dosages of amoxicillin can achieve effective middle ear fluid concentrations, an increase in the dosage used for empiric treatment from 40 to 45 mg per kg per day to 80 to 90 mg per kg per day is recommended. For patients with clinically defined treatment failure after 3 days of therapy, useful alternative agents include oral amoxicillin clavulanate, cefuroxime axetil and intramuscular ceftriaxone. Many of the 13 other FDA approved otitis media drugs lack good evidence for efficacy against DRSP. Currently local surveillance data for pneumococcal resistance that are relevant for the clinical management of AOM are not available from most areas in the U.S. Recommendations to improve surveillance include establishing criteria for setting susceptibility breakpoints for clinically appropriate antimicrobials to ensure relevance for treating AOM, testing middle ear fluid or nasal swab isolates in addition to sterile site isolates and testing of drugs that are useful in treating AOM. The authors stress that these recommendations are intended to provide a framework for appropriate clinical and public health responses to this problem. 4 tables. 59 references. (AA-M).

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Acute Otitis Media: Update on How and When to Give Antibiotics Source: Consultant. 36(4): 721-728. April 1996. Summary: This article updates readers on the use of antibiotic therapy for acute otitis media (AOM) in children. The authors note that the emergence and global spread of antibiotic-resistant bacteria have prompted a thoughtful re-evaluation of optimal diagnostic criteria and indications for treatment. Diagnosis is most certain when the tympanic membrane is discolored, bulging, and immobile. Once the diagnosis of AOM is established, antibiotic treatment is a reasonable, but not necessary, option. Amoxicillin remains the drug of first choice; trimethoprim-sulfamethoxazole is an appropriate second choice for apparent treatment failure due to beta-lactamase-producing bacteria. The authors stress that the goal in AOM is effective treatment while decreasing the impact of antbiotic therapy on the selection of resistant pathogens. This can be achieved through accurate diagnosis of AOM, coupled with judicious use of antibiotics and a decreased duration of therapy. 2 figures. 2 tables. 31 references. (AA-M).

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Treatment of Acute Otitis Media and its Complications Source: Otolaryngologic Clinics of North America. 27(3): 431-441. June 1994.

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Summary: This article, from a special issue on pediatric otology, discusses the treatment of acute otitis media (AOM) and its complications. Topics covered include diagnostic considerations; pathogenesis; epidemiologic factors; microbiology; AOM in neonates; treatment options; the role of tympanocentesis; recurrent otitis media; complications, including intratemporal complications, and intracranial complications; and prevention, including environmental factors and vaccines. 2 figures. 27 references. •

Use of Antibiotics in Preventing Recurrent Acute Otitis Media and in Treating Otitis Media with Effusion: A Meta-Analytic Attempt to Resolve the Brouhaha Source: Journal of the American Medical Association. 270(11): 1344-1351. 1993. Summary: This article, written for health professionals, is a review of selected studies that were looked at to determine the efficacy of antibiotics for prophylaxis of recurrent otitis media and treatment of otitis media with effusion in children. Results of this review indicated that antibiotics appear to have beneficial but limited effect on recurrent otitis media and short-term resolution of otitis media with effusion. Longer-term benefit for otitis media with effusion has not been shown. Bibliographic references are included.

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Acute Suppurative Otitis Media Source: ENT. 72(6): 387. 1993. Summary: This brief article, written for health professionals, describes the origin of acute suppurative otitis media, lists the six stages of acute otitis media, and describes the otoscopic view of the tympanic membrane with this condition. A picture of the ear during the stage of exudation is included.

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Chronic Otitis Media with Effusion Source: Pediatrics in Review. 20(3): 85-93. March 1999. Contact: Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. Summary: This continuing education article for pediatricians reviews chronic otitis media with effusion (OME). The authors break down the percent of cases of chronic OME that yield bacterial growth on culture and discuss which bacteria they yield. The authors then describe the effects of antibiotic treatment for acute OM on the long term resolution of middle ear effusion (MEE). The authors also list the risk factors that increase the duration of OME and the risk of chronic OME, as well as detail the percentage of children who experience hearing loss following chronic OME. The authors conclude by reviewing the care of the child who requires referral to an otolaryngologist for myringotomy with insertion of ventilation tubes. The authors caution that antibiotic treatment of acute otitis media and OME has only a minimal effect on the long term resolution of MEE. If the child has hearing impairment, referral to an otolaryngologist for myringotomy and tympanostomy tube insertion is a treatment option that is recommended after 4 months of effusion with hearing loss. Sequelae of chronic OME include deficient expressive language and poorer attention skills due to the temporary hearing loss associated with OME, high frequency sensorineural hearing loss, tympanic membrane atrophy, perforation, retraction, atelectasis, and cholesteatoma. 9 figures. 2 tables. 13 references.

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Role of IgE-Mediated Hypersensitivity in the Development of Otitis Media with Effusion: A Review Source: Otolaryngology: Head and Neck Surgery. 109(3 Part 2): 611-620. September 1993. Summary: This review article examines the role of immunoglobulin E-mediated hypersensitivity in the development of otitis media with effusion. The author emphasizes that this hypersensitivity or allergy represents only one variable in a very complex disease entity. Bacterial infection, viral infection, and mucociliary clearance are important variables that must be considered and that may be affected by the allergic response. On the basis of the world literature and on laboratory investigations at the Children's Hospital of Buffalo, the author concludes that otitis media is associated with allergy in 35 to 40 percent of cases. 8 figures. 4 tables. 23 references. (AA-M).

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Management of Otitis Media: 2000 and Beyond Source: Pediatric Infectious Disease Journal. 19(4): 383-387. April 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: This review article provides an overview of the management of acute otitis media (AOM, middle ear infection) in which the author offers his assessment of future trends in diagnosis and therapy. Bacteria and viruses will continue to find ways to survive the activity of currently available antimicrobial drugs. Among the new antimicrobial drugs under consideration are ketolides, oxazolodinones, and quinolones. Guidelines stress limiting usage of antimicrobial agents to diseases that are likely caused by bacterial pathogens. Antiviral drugs are now available against influenza virus and respiratory syncytial virus infections. Tympanometry or acoustic reflectometry are adjunctive techniques for assisting in the diagnosis of middle ear effusion in children whose otoscopic examination is ambiguous. The author notes that parents influence decisions by pediatricians to use antimicrobial agents and should be informed about the appropriate usage of antibiotics. Educators and public health officials must find techniques to distinguish web sites that provide information of value from those that are not credible. Of paramount importance is the development of techniques to increase the accuracy of clinical and microbiologic diagnosis. Finally, there is a need for studies of appropriate scientific design that can assess the efficacy and safety of alternative therapies. 2 tables. 19 references.

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Role of Allergy in Eustachian Tube Blockage and Otitis Media with Effusion: A Review Source: Otolaryngology-Head and Neck Surgery. 114(4): 562-568. April 1996. Summary: This review article suggests that the observed relationship between allergy and otitis media with effusion (OME) is caused by mediators of inflammation, cytokines, and colony-stimulating factors released by mucosal mast cells and other inflammatory and epithelial cells in the nose and nasopharynx. These mediators produce blockage of the eustachian tube through a number of mechanisms, which may include local injury or vascular-or neural-mediated changes. The author notes that it is likely that the nasal allergic response in patients predisposes to eustachian tube blockage and, if prolonged, causes changes in gas absorption in the middle ear space. This persistent underpressure will then lead to middle ear effusion. The author concludes that, irrespective of the theoretical mechanism, the relationship between

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allergy and OME will remain controversial until well-controlled clinical studies are conducted documenting that in select populations antiallergy therapy is efficacious in preventing or limiting the duration of OME. 3 figures. 4 tables. 28 references. (AA-M0. •

Medical and Surgical Management of Otitis Media Source: Current Opinion in Otolaryngology and Head and Neck Surgery. 8(6): 458-464. December 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: This review article summarizes the latest research on the diagnosis and medical and surgical management of otitis media. Acute otitis media (AOM), which is the most commonly diagnosed medical problem in children, is an acute inflammation of the middle ear cleft with systemic signs of inflammation. Several investigators studied the risk factors for otitis media during the year 2000. One researcher found that otitis media with effusion (OME) was strongly associated with age, early gestational age, low birth weight, enrollment in day car, number of siblings, and cold weather. Another researcher found a strong genetic basis for OME and AOM. Other investigators have reported on the value of tympanometry and reflectometry in the diagnosis of OME. Other areas of scientific inquiry during the year 2000 focused on the influence of allergy on otitis media, middle ear pathogens, and the role of middle ear inflation in the prevention of OME. Oral antibiotics continue to be heavily used in the United States, and AOM may be overdiagnosed. Several investigators reported work on S. pneumonia drug resistance and altered strategies for antibiotic use. In addition, a new conjugated heptavalent pneumococcal vaccine was evaluated during the year. Other research conducted during the year 2000 addressed the efficacy of tympanostomy tubes, the occurrence and prevention of tympanostomy tube complications, and the use of adenoidectomy and laser assisted myringotomy as treatments for OME. 1 table. 49 references.

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Recent Advances in Otitis Media Treatment Source: Annals of Otology, Rhinology and Laryngology. 103(5 Part 2, Supplement 163): 1-64. May 1994. Summary: This special issue of the Annals of Otology, Rhinology, and Laryngology reprints presentations from the Symposium on Recent Advances in Otitis Media Treatment, a conference held in October 1993 in Minneapolis, Minnesota. Fourteen papers are reprinted, covering new developments in treating otitis media; the antimicrobial treatment of acute otitis media; the role of IgE-mediated hypersensitivity in otitis media with effusion (OME); preventing otitis media; the pathology of otitis media; tympanic membrane perforations and tympanostomy tubes; the tympanometric evaluation of middle ear function in children with otitis media; risk factors for otitis media sequelae and chronicity; determining otitis media severity from middle ear fluid analysis; the sustained release of antimicrobials in the middle ear using a biodegradable support; surgical advances in treating otitis media; adenoidectomy for OME; and the identification of hearing loss in children with otitis media. The issue also reprints the morning and afternoon panel discussions held at the Symposium.

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Prevalence of Various Respiratory Viruses in the Middle Ear During Acute Otitis Media Source: New England Journal of Medicine. 340(4): 260-264. January 28, 1999.

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Summary: Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media. Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown. This article reports on a study that determined the prevalence of various respiratory viruses in the middle ear fluid of 456 children (aged 2 months to 7 years) with acute otitis media (AOM). At enrollment and after two to five days of antibiotic therapy, specimens of middle ear fluid and nasal wash were obtained for viral and bacterial cultures and the detection of viral antibodies. A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent). Respiratory syncytial virus was the most common virus identified in middle ear fluid: it was detected in the middle ear fluid of 48 of the 65 children (74 percent) infected by this virus. Parainfluenza viruses (15 of 29 children, or 52 percent) and influenza viruses (10 of 24 children, or 42 percent) were detected in the middle ear fluid significantly more often than enteroviruses (3 of 27 children, or 11 percent) or adenoviruses (1 of 23 children, or 4 percent). The authors conclude that respiratory syncytial virus is the principal virus invading the middle ear during acute otitis media. An effective vaccine against upper respiratory tract infections caused by respiratory syncytial virus may reduce the incidence of AOM in children. 3 tables. 37 references. (AA-M). •

Viral and Bacterial Interaction in Acute Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S24-S30. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: Viral infection of the upper respiratory tract induces Eustachian tube dysfunction and microbial invasion of the middle ear. These conditions lead to acute inflammatory changes and signs and symptoms of middle ear infection. By the time acute otitis media (AOM, middle ear infection) is diagnosed, viral infection of the upper respiratory tract may have been aborted, and the virus may never enter the middle ear. If the virus enters the middle ear along with bacteria or if the viral upper respiratory tract infection is still ongoing at the time of AOM diagnosis, evidence suggests that the virus may interact with the bacteria, leading to adverse outcomes of AOM. This review article discusses clinical evidence of viral and bacterial interaction that occurs by the time AOM has been developed, effects of the interaction on the clinical course of AOM and recovery, and potential mechanisms of the interaction. The author concludes that AOM, which is generally considered a bacterial disease, is more likely a bacterial complication of viral upper respiratory tract infection. More sensitive methods for detection of a wide variety of viruses in a uniform manner are needed to help clarify the relative significance of each virus type. 5 tables. 58 references.

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Hearing Results of Surgery for Chronic Otitis Media Without Cholesteatoma Source: ENT. Ear, Nose, and Throat Journal. 74(3): 165-169. March 1995. Summary: While otologists are well aware of the potentially dangerous, even lifethreatening risks of chronic otitis media, patients often are mainly concerned about the hearing loss caused by this disease because other symptoms of chronic otitis media usually are minor or lacking. This article reports on a study that evaluated the hearing results of surgical treatment for chronic otitis media and its sequelae in 569 patients. Cases of cholesteatoma were excluded because of the special problems associated with this disease. The mean follow up period was 5.2 years. Ears with intact ossicular chain showed the best postoperative hearing function. Satisfactory hearing results were

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obtained in 68 percent of ears with eroded ossicles but intact stapes and in only 50 percent of ears with loss of stapes superstructure. Cases of sequelae to otitis showed better hearing results than cases of granulating otitis media. At last follow up examination, 72 percent of the whole series had hearing levels of 30 dB or better. 5 tables. 3 references. (AA-M). •

Otitis Media: To Treat or Not to Treat? Source: Consultant. 38(6): 1421-1424, 1426, 1432-1433. June 1998. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. (203) 661-0600. Summary: With the emergence of bacterial pathogens that are resistant to antimicrobial agents, there has been a recent call for more rational use of these drugs for the treatment and prevention of otitis media. This article reviews the issue of whether to treat otitis media with antibiotics. The author concludes that, despite the proposal by some to withhold antibiotics when acute otitis media occurs, there is now sufficient evidence of efficacy to warrant their use. However, it is crucial to distinguish acute otitis media from the relatively asymptomatic otitis media with effusion, which is usually not treated unless the effusion becomes chronic. Amoxicillin remains the therapy of choice. Alternative agents should be reserved for cases in which signs and symptoms of infection progress after amoxicillin treatment. To reduce antibiotic use, prophylactic therapy should be given to prevent recurrent otitis media only on an individual basis. Tympanostomy tube placement may be a more reasonable alternative. The author reiterates that acute otitis media is overdiagnosed and all otitis media is overtreated with antibiotics. 2 figures. 3 tables. 20 references. (AA-M).

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Novel Use of Xylitol Sugar in Preventing Acute Otitis Media Source: Pediatrics. 102(4): 879-884. October 1998. Contact: Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. Summary: Xylitol, a commonly used sweetener, is effective in preventing dental caries. This article reports on a study that evaluated whether xylitol could be effective in preventing acute otitis media (AOM), as it inhibits the growth of pneumococci. In all, 857 healthy children recruited from day care centers were randomized to one of five treatment groups to receive control syrup (n = 165), xylitol syrup (n = 159), control chewing gum (n = 178), xylitol gum (n = 179) or xylitol lozenge (n = 176). The daily dose of xylitol varied from 8.4 g (chewing gum) to 10 g (syrup). The occurrence of AOM each time the child showed any symptoms of respiratory infection was the main outcome. Although at least one event of AOM was experienced by 68 (41 percent) of the 165 children who received control syrup, only 46 (29 percent) of the 159 children receiving xylitol syrup were affected, for a 30 percent decrease. Likewise, the occurrence of otitis decreased by 40 percent compared with control subjects in the children who received xylitol chewing gum and by 20 percent in the lozenge group. Thus, the occurrence of AOM during the follow up period was significantly lower in those who received xylitol syrup or gum, and these children required antimicrobials less often than did controls. Xylitol was well tolerated. 3 figures. 3 tables. 26 references. (AA-M).

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

Project Title: A RANDOMIZED CONTROLLED TRIAL OF ECHINACEA IN CHILDREN Principal Investigator & Institution: Taylor, James A.; Pediatrics; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: Upper respiratory tract infections (URI's) are a significant health burden in childhood. URI's are a major reason for visits to health care providers, and up to 35% of young children at any given time are taking some over-the-counter cold medication. Unfortunately, data suggest that most of these medications have limited effectiveness. Alternative medical therapies are growing in popularity; in a recent survey of parents of children being seen by pediatricians in Seattle, Washington, 24.2% indicated that their child had been seen by an alternative medicine health care provider, and 53.3% therapies for the treatment of URI's in children. The proposed study is a randomized, double blind, placebo controlled trial of echinacea for the treatment of URI's in children 2-11 years old. The aims of the project are: to determine if echinacea shortens the duration and/or lessens the severity of URI's, if children receiving echinacea for treatment of URI's have a reduced rate of secondary bacterial infections, and to determine if the use of echinacea in patients 2-11 years old is associated with any significant side effects. A two-year study of 600 children is planned. Not only will the results of this study will determine if echinacea, the most popular medicinal herb sold in the United States, is an effective therapy for URI's in children, the study will provide a design framework for future assessments on the efficacy of other complementary and alternative medicines in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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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Project Title: ACUTE OTITIS MEDIA--ADJUVANT THERAPY TO IMPROVE OUTCOME Principal Investigator & Institution: Chonmaitree, Tasnee; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001 Summary: This study will evaluate in young children the effectiveness of new therapies for acute otitis media (AOM) which, when used in addition to standard antibiotic therapy, may help to control the actions of substances within the middle ear which appear to prolong middle ear disease. Antihistamines and corticosteriods, used separately or together in addition to antibiotic drugs, will be tested in two groups of children with acute otitis media of bacterial and/or viral origin. A group of 72 infants enrolled at the beginning of their first episode of AOM will be evaluated for organisims and substances in their middle ear fluids prior to and 5 days after drug treatment; a larger group of 200 children with histories of recurrent otitis media will be treated with the drugs and evaluated over a six month period for treatment outcome, duration of fluid in the ear, and recurrence of disease. This study should clarify the potential benefits and mechanisms of action of antihistamines and corticosteriods in the treatment of AOM, and may establish their usefulness in the prevention of recurrent or prolonged ear disease in young children. To date we have not completed enrollment of the children, therefore data have not been analyzed. Identification of improved therapies for otitis media is a very high priority because nearly all young children experience this disease, and some suffer from multiple or prolonged episodes of illness which require expensive and invasive treatment, disrupt family life, and may interfere with normal development of language and cognitive skills. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADAPTATION PATHOGENESIS

TO

ANAEROBIOSIS

IN

H

INFLUENZAE

Principal Investigator & Institution: Tyler, Ryan E.; Microbiology and Immunology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-MAY-2002 Summary: (provided by applicant): Haemophilus influenzae is a common asymptomatic colonizer of the upper respiratory tract, yet also causes a range of invasive diseases such as otitis media, a middle ear infection that produces acute pain, distress and temporary or permanent hearing loss in children. The presence of obligate anaerobic species with H. influenzae in the middle ear fluid and the nasopharynx of otitis media patients indicates that H. influenzae encounters low oxygen conditions in vivo. H. influenzae possesses redox-responsive systems found in several other bacterial pathogens. The participation of these redox-responsive systems in altering global gene expression in response to oxygen deprivation will be investigated by characterizing the expression profiles of the nitrate and nitrite reductases. Preliminary data indicate that nitrate and nitrite reductase expression in H. influenzae is mediated by environmental signals, such as substrate availability and environmental oxygen levels. Additionally, the in vitro characterization of the nitrate and nitrite reductase expression profiles permits the development of the reductase-encoding genes as reporters for the physiological state of H. influenzae during infant rat infection. Therefore, the importance of this study is to not only yield insight into the regulatory processes of redox sensing in H. influenzae, but also to characterize the physiological state of this bacterium within host niches.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADENOIDECTOMY FOR OTITIS MEDIA IN 2/3 YEAR OLD CHILDREN Principal Investigator & Institution: Casselbrant, Margaretha L.; Professor; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2004 Summary: Efficacy of adenoidectomy for the treatment and prevention of otitis media with effusion has been shown for children four years and older. In their "Clinical Practice Guidelines, Otitis Media with Effusion in Young Children", the Agency for Health Care Policy and Research of the U.S. Department of Health and Human Services concluded that "Adenoidectomy is not recommended for treatment of OME in a child age 1 through 3 years in the absence of specific adenoid pathology". This conclusion was based on the Panel's finding no clinical trials to support any judgement as to the efficacy of adenoidectomy in the primary management of otitis media with effusion in very young children, coupled with the risk of postoperative bleeding. By means of a well designed large-scale randomized controlled trial, the efficacy of adenoidectomy and myringotomy with and without tympanotomy tube insertion will be compared with that of myringotomy and tympanotomy alone in reducing the morbidity of bilateral otitis media with effusion of at least 3 months's duration associated with hearing loss (>20 dB) in children ages 2 and 3 years. The primary outcome measure will be percentage of time with middle ear effusion. Rates of episodes of acute otitis media, otorrhea, and otitis media with effusion, time to first recurrence, number of surgical procedures, treatment failures, hearing status, and other sequelae and complications will be recorded and compared among the three treatment groups. We estimate that 63 evaluable subjects need to be entered in each treatment arm to have a 90 percent power of detecting a benefit of at least 0.30 in percentage of time with middle ear effusion. The outcome of this trial should resolve the question of efficacy of adenoidectomy for otitis media with effusion in this age group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AIR INFLATION EFFICACY--CORTICOSTEROID THERAPY OF OTITIS MEDIA WITH EFFUSION Principal Investigator & Institution: Alper, Cuneyt M.; Associate Professor; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001 Summary: Otitis Media with Effusion (OME) is a common disease in the pediatric age group and remains refractory to current medical tretments. Middle ear (ME) pressure regulation is central to the maintenance of mucosal health, and dysregulation both promotes and is a consequence of OME. These considerations have generated a renewed interest in alternative non-invasive methods of maintaining stable ME pressures to prevent or treatment OME. In that regard, a variety of methods to introduce gas via the Eustachian tube, into the diseased ME has been described. However, the results of clinical studies are contradictory with reports of both no benefits of these procedures as well as high clinical cure rates for established OME. Theoretical considerations and experimental results show that the ME inflation protocols can be modified with respect to timing so as to optimize their expected physiological effect and thus their efficacy for treatment OME. However, in the absence of resolution of the underlying inflammation and/or restoration of good ME pressure regulating function, the disease is expected to

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recur quickly after termination of the inflation maneuvers. This is supported by the results of clinical studies that reported high recurrence rates upon discontinuing inflation. Consequently, a two-pronged intervention strategy including repeated ME air inflation to preserve ambient pressures and anti-inflammatory treatment to resolve the underlying mucosal inflammation may provide the best hope for curing persistent OME. That strategy is tested a proof-of-concept in this proposed clinical trial. Children with documented OME of at least two months duration will be randomized to receive antibiotic treatment + placebo inflation + placebo steroid (standard of care), or antibiotic + ME air inflammation + placebo steroid, or antibiotic + ME air inflation + oral corticosteroids for a one month treatment period. The cure rte for OME will be evaluated at the end of treatment and recurrence rates measured at 8 and 12 week follow-up visits. The hypotheses tested are that: 1) the two groups treated with air inflation will have comparable cure rates that are significantly greater than that of the antibiotic treatment group, and, 2) disease recurrence will be significantly greater in the group treated with inflation and placebo when compared to that treated with inflation plus corticosteroids. While primarily an evaluation of treatment efficacy for persistent OM, this study also represents a formal test of the predictive accuracy of the underlying model of disease pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APPROPRIATE PNEUMOCOCCAL VACCINATION IN INFANTS IN FIJI Principal Investigator & Institution: Mulholland, Edward K.; University of Melbourne Parkville 3052, Australia Parkville, Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccines are safe, immunogenic, and effective. However, the vaccine is very expensive (approximately USD $200/infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver this vaccine, which are safe and effective. A recent World Health Organization (WHO) / Global Alliance for Vaccines and Immunization (GAVI) meeting to address impediments to the introduction of these vaccines in developing countries recognized the need to evaluate other regimens of Pnc conjugate vaccine as an important research priority. This study has been deliberately formulated with that need in mind. The proposed site for this research is Fiji. Although health services are good, Pnc disease, particularly pneumonia, remains the commonest cause of childhood morbidity and mortality. Fiji has good vaccine coverage and was the first Pacific country to introduce Hib vaccine. The arrival of the new, expensive Pnc conjugate vaccine presents a dilemma for Fiji and many similar countries. The expense of this vaccine if used in the recommended 3 or 4-dose schedule would consume a large portion of the health budget. This study has two components, aimed at addressing these two issues:1. A phase 2 immunogenicity study (involving 750 infants) to evaluate regimens using reduced numbers of doses of Pnc conjugate vaccine, and using timing of dosing and combinations with polysaccharide (PS) vaccine that may be more suited to the epidemiology of Pnc disease in developing countries.2. An epidemiological study will measure the burden of invasive Pnc disease, pneumonia, and otitis media (OM) in Fiji.

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This will be part of a global effort to address these issues, and will be used to develop rapid assessment tools for these diseases in developing countries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSESSMENT OF MIDDLE EAR FUNCTION Principal Investigator & Institution: Margolis, Robert H.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BACTERIAL PHOSPHORYLCHOLINE AND PATHOGENESIS Principal Investigator & Institution: Weiser, Jeffrey N.; Associate Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Description (Adapted from Applicant's Abstract): The bacterial cell surface is generally considered to be highly divergent from species to species. An exception to this rule is the expression of phosphorylcholine (ChoP). This unusual prokaryotic structure is now known to be exposed on the surface of the most common pathogens infecting the human respiratory tract; Haemophilus influenzae, mycoplasma, and Streptococcus pneumoniae. In addition, based on cross-reactivity to a MAb recognizing this structure, ChoP may be present on diverse phase-variable structures on N. meningitidis, N. gonorrhoeae, P. aeruginosa, and A. actinomycetemcomitans. We have defined the genetic basis of ChoP expression and the molecular mechanism controlling its phase variation in H. influenzae. This has allowed direct genetic analysis of clinical samples to show that the ChoP+ phase variants predominate on the mucosal surface of humans. The structure, however, is the target of innate immunity mediated by binding of C-reactive protein (CRP), which is bactericidal in the presence of complement. The focus of this proposal is to define the biological role of variants both with and without ChoP using H. influenzae as a prototype human respiratory tract pathogen. In Aim 1, we will determine whether switching to the ChoP- phenotype is required in natural H. influenzae infection (otitis media, pneumonia, bacteremia, and meningitis) to evade clearance by CRP and bactericidal anti-ChoP IgG. The ChoP phenotype in vivo will be determined by direct genetic analysis and compared to the local concentration of CRP and anti-ChoP antibody during infection. The local expression and concentration of CRP in the upper respiratory tract will be investigated. In Aim 2, we will determine how ChoP contributes to persistence on the mucosal surface. Genetically defined H. influenzae mutants with constitutive ChoP-on and ChoP-off phenotypes will be used to determine whether this host membrane-like structure contributes to (a) resistance to respiratory tract antibacterial peptides including LL-37 and tracheal antimicrobial peptide (TAP), and (b) colonization by functioning as a bacterial adhesin to host epithelial cells via putative ChoP ligands including GalNAcb 14Gal on the asialo-GM1 glycolipid and the platelet activating factor receptor. The blocking of complement mediated killing by naturally acquired secretory IgA recognizing ChoP will be explored as an explanation for the selection of the ChoP+ phenotype on the mucosal surface, despite the increased susceptibility of this phenotype to CRP and complement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BASIC AND CLINICAL STUDIES IN OTITIS MEDIA Principal Investigator & Institution: Doyle, William J.; Professor; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001; Project Start 01-APR-1992; Project End 30-JUN-2003 Summary: Otitis media (OM) is the most common disease for which children receive medical care in the United States. Complications and sequelae of OM contribute significantly to pediatric morbidity and impose a large economic burden on society. Despite these costs, persistent OM remains refractory to conventional medical treatment and disease pathogenesis is not well understood. This proposal requests 5 years of support for an existing research program focused on OM pathogenesis with the overall goal of designing rational interventions to abort or moderate that process. The program includes four projects and two supporting core units (Administration and Biostatistics). An understanding of middle ear (ME) pressure regulation in health and disease is the main theme underlying the four Projects. In that regard, clinical and experimental evidences support a central role for imbalances in ME pressure regulation as: an initiator of the disease process, a pathophysiological consequence of OM caused by other etiologies, and a promoter of disease persistence. Adequate pressure regulation requires maintaining a dynamic balance between the ME gas volume depleted by diffusive exchange and the gas volume supplied during openings of the Eustachian tube (ET). These two components of ME pressure regulation are quantitatively defined in experiments conducted under Projects of this Program. From these data, current mathematical models of ME pressure regulation will be refined and prognostic tests of dysregulation will be developed and evaluated in the ME pressure regulation will be refined and prognostic tests of dysregulation will be developed and evaluated in the clinical setting. The biochemical and pathophysiological mechanisms by which demandsupply imbalances provoke ME mucosal inflammation and OM are examined. The overall goals of that project are to define signal transduction pathways and to identify pathway components that could represent targets for pharmacological intervention. A clinical trial evaluates a promising OM treatment strategy based on the predictions of a model of disease pathogenesis that synthesizes the results of earlier studies conducted under this Program. While primarily an efficacy trial of repeated ME inflation for treatment of OM, that study also represents a formal test of the predictive accuracy of the underlying model. Successful completion of these Projects will provide a better understanding of OM pathogenesis, develop prognostic tests of ME health, and define rational intervention strategies for continued study in the clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BETA-DEFENSINS AND PULMONARY HOST DEFENSE Principal Investigator & Institution: Starner, Timothy D.; Pediatrics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in the basis sciences. The principal investigator has completed his training in Pediatrics and sub-specialty training in Pediatric Pulmonology at the University of Iowa and now is focusing on developing his basic science knowledge and laboratory experience to become an independent investigator. This program involves pulmonary innate immune factors and how they interact with bacterial pathogens. Dr. Paul McCray will mentor the principal investigator's scientific development. Dr. McCray is a recognized leader in the field of

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pulmonary innate immunity with emphasis on the role of antimicrobial peptides such as the beta-defensins. Dr. Michael Apicella will act as co-mentor. He is the Department Head of Microbiology at The University of Iowa and is a renowned expert on Haemophilus influenzae. His work has focused on. the antigenic structure of Haemophilus membrane components and their relationship to disease. In addition, an advisory committee of highly-regarded medical scientists will provide scientific and career advice. Dr. Starner's research will investigate the interactions between pulmonary innate immune factors and nontypeable H. influenzae (NTHi), a common diseaseassociated pathogen in otitis media, COPD and cystic fibrosis. His recent work demonstrated that the hexaacylation of lipid A is an important determinant of the antimicrobial sensitivities toward specific beta-defensins. The proposed experiments will investigate outer membrane changes and potential binding sites of the betadefensins on laboratory, mutant and clinical strains using microbiologic, biochemical, and sub-proteomic approaches. Two specific aims will be addressed: 1) identify the specific cell wall component(s) of NTHi that interact with human beta-defensins; and 2) determine the effects of human beta-defensin exposure on NTHi outer membrane protein and LOS expression. These will be the first studies on the interactions between NTHi and the beta-defensins. The University of Iowa provides an ideal environment for this proposal because of the Pediatrics and Microbiology Departments' strong track records in research and the outstanding mentors selected. This environment will maximize the potential for the principal investigator to establish himself in a basic science career as an academic independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR AND MOLECULAR BIOLOGY OF CHOLESTEATOMA Principal Investigator & Institution: Chole, Richard A.; Lindburg Professor and Head; Otolaryngology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 30-JUN-2003 Summary: Aural cholesteatomas arise from the tympanic membrane as a sequela of otitis media. Cholesteatomas are progressive, epithelial lesions that destroy the bony structures of the middle and, sometimes, inner ear. Once established, cholesteatomas can only be mandated by surgical eradication and secondary middle ear reconstruction. The long-term objective of the Principal Investigator's research program is to understand the cellular mechanisms that lead to the development, progression, and bone destruction of cholesteatomas. Such an under- standing may lead to strategies for the non-surgical prevention and management of this disease. The present application is designed to investigate the relationship of two important intercellular signaling molecules, interleukin-1 (IL-1) and nitric oxide (NO), to osteoclastic bone erosion in cholesteatoma. The specific aims of this application are: 1) to determine the expression of the interleukin family of cytokines (IL-1 alpha, IL-1 beta, and IL-1ra) in experimental cholesteatoma and also during osteoclast recruitment and activation induced by pressure in the gerbil bulla model of synchronous bone modeling; and 2) to investigate isoforms of nitric oxide synthase (NOS I, II, III) in the local control of osteoclasts in vitro and in vivo. There are two broad hypothesis, each focused on the isoforms of IL-1 and NOS. For Specific Aim1, hypothesis 1 will be tested: IL-1 isoforms are transcribed within bone lining cells and fibroblasts of the sub- epithelium subjacent to cholesteatoma and in the pressurized bulla and represent an early signal for the recruitment and activation of osteoclasts at a local site. Experimental gerbilline cholesteatoma, gerbilline pressurized bulla, PCS, cloning of PCR products, DNA sequencing, quantitative RT-PCR, bone histomorphometry, and RNA in situ hybridization will be used to test this first

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hypothesis. For Specific Aim 2, hypothesis 2 will be tested: NO is produced by upregulation of NOS isoforms within bone lining cells and fibroblasts of the subepithelium subjacent to cholesteatoma and in the pressurized bulla. This leads to the local elaboration of NO and the recruitment and activation of osteoclasts. Mouse calvarial organ culture (elemental calcium release and 45Ca release), gerbilline pressurized bulla, PCR, cloning of PCR products, DNA sequencing, quantitative RTPCR, bone histomorphometry, RNA in situ hybridization, and NADPH- diaphorase histochemistry will be used to test this second hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CENTRAL DEPRIVATION

AUDITORY

SYSTEM

EFFECTS

OF

AUDITORY

Principal Investigator & Institution: Tucci, Debara L.; Associate Professor of Surgery; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant):The long-term goal of this work is to understand the structural and functional changes imposed on the central auditory system by conductive hearing impairment. A secondary goal is to determine the factors that govern the potential for reversibility of these changes. The clinical implications of this work are that many children experience conductive hearing loss during early development, in a time period that coincides with that of rapid acquisition of speech and language skills. Childhood conductive hearing loss is known to be associated with deficits in auditory processing skills, some of which persist even after the return of normal hearing. The nature of the functional and neuroanatomical changes in the central auditory system that underlie these deficits is unknown. The hypothesis underlying this proposal is that chronic conductive hearing impairment in early life results in structural changes in the central auditory systems, which are related to functional deficits in central auditory processing. These effects are age-dependent, and more severe in the developing animal. The severity of the structural change will affect the potential for reversibility when normal hearing is reinstated. Experiments are proposed to achieve three specific aims designed to address this hypothesis: 1) to define the effects of conductive hearing loss on activity in the auditory nerve and central auditory system, and assess the agedependent interactions; 2) to define the metabolic and structural changes that occur following unilateral conductive hearing loss in the developing and mature animal; and 3) to investigate factors that govern the reversibility of the above changes. We hypothesize that the potential for reversibility will depend upon the type and severity of the structural modification induced by conductive impairment, and the developmental stage of the animal at the time of the insult. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OSTEOCLASTS

OF

NOS

I

SPLICE

VARIANTS

IN

Principal Investigator & Institution: Jung, Jae Y.; Otolaryngology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-FEB-2002 Summary: (provided by applicant): Chronic otitis media with and without cholesteatoma can lead to conductive as well as sensorineural hearing loss as the result of inflammatory bone resorption in the middle ear. Conductive hearing loss is commonly caused by erosion of the ossicles resulting from the inappropriate activation

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of osteoclasts. A number of factors regulate osteoclast development and activation including hormones, growth factors and cytokines. Recently, nitric oxide (NO) has been shown to play a role in osteoclast activation. NO is a short-lived neutral free radical gas synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). The mechanism by which nitric oxide mediates osteoclast function is not well characterized and the three known isoforms may have opposing effects. In neurons, NOS I has extremely complex transcriptional and translational regulatory mechanisms involving multiple alternate splice variants, which are expressed in a stage and tissue specific manner. Preliminary results in our laboratory demonstrate NOS I-/ -osteolcasts have an in vitro and in vivo phenotype, suggesting NOS I plays an important role in osteoclast function and that this role may be mediated by a unique splice variant of this enzyme. The specific aims of this proposal are 1) to identify the alternate splice variant(s) expressed in osteoclasts and 2) to initiate the characterization of the translated NOS I protein. In addition to providing a understanding of the molecular mechanisms underlying cholesteatoma-induced bone resorption, the identification and characterization of unique transcriptional and translational NOS I regulatory mechanisms may facilitate the discovery of novel, osteoclast-specific pharmaceutical targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILD DEVELOPMENT IN RELATION TO EARLY OTITIS MEDIA Principal Investigator & Institution: Paradise, Jack L.; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001; Project Start 01-JUN-1991; Project End 31-JAN-2002 Summary: (Adapted from the Investigator's Abstract): This application is for continuing support of a study, initiated in June 1991, whose main objectives are to determine whether persistent otitis media with effusion (OME) during the first 3 years of life results in lasting impairments of speech, language, cognitive, or psychosocial development, and if so, whether prompt tympanostomy-tube placement (TTP) prevents or lessens the impairments. Secondary objectives are to determine whether increasing the duration of OME required before undertaking TTP results in fewer operations or in altered long-term otologic or audiologic outcomes, and to chart the occurrence and course of otitis media (OM) and associated hearing loss in young children, distorted as little as possible by surgical interventions. Previous studies of OM in relation to later developmental impairment have been inconclusive and contradictory, and unsuited, because of their associational design, to address the issue of causality. A total of 6400 well infants aged 8 wk duration audiometry is scheduled monthly. Up to age 3 yr, children who reach specified criteria regarding persistent OME are, subject to consent, randomized to receive TTP either promptly ("early-TTP") or after a defined extended period if OME remains present ("late-TTP"). Thus a high-OME population is divided into 2 groups who can be assumed to have equivalent developmental potential: an earlyTTP group most of whom become relatively OM-free, and a late-TTP group most of whom continue to have OM for varying periods. If the late group subsequently has less favorable developmental outcomes, persisting OM will presumably have been causal. Development is assessed subjectively in all subjects at ages 1 and 2 yr via parent questionnaires. Formal tests of speech, language, cognition, and psychosocial development are administered at ages 3, 4, and 6 yr to all subjects who had met randomization criteria and to a sample of others representing a spectrum of OME experience. Analyses of test results in these groups will enable determinations of whether associations, either short- or long-term, exist between persistent early OME and

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later developmental impairments; if so, whether the associations are causal; and whether prompt TTP is effective in preventing or lessening such impairments. As of Oct 5, 1995, 6030 children had been enrolled, 376 had met randomization criteria, and 292 had been randomly assigned to early- or late-TTP groups. Analyses to date have provided new information about the epidemiology of OM, about the diagnostic predictive value of tympanometry, and about correlations between cumulative OME duration and language and behavior at ages 1 and 2 yr. If continued, this study will provide new knowledge that will make possible more rational, evidence-based management of OM in infants and young children, and thereby benefit children and substantially influence child health care practices and costs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISORDERS

CLINICAL

RESEARCH

CENTER

FOR

COMMUNICATIVE

Principal Investigator & Institution: Ruben, Robert J.; Professor and Chairman; Otolaryngology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-SEP-1983; Project End 30-JUN-2002 Summary: The overall purpose of this proposal is to examine the effects of early auditory input on the acquisition of normal speech and language, and how alterations in this input can contribute to language impairment. A child~s hearing status, auditory history (i.e., history of otitis media with effusion), ability of the child to process nonspeech auditory signals (i.e., simple and complex tones), ability to process speech signals without attached meaning, ability to process meaningful language, and exposure to a second language all can affect normal language development. To understand language and its disorders it is necessary to examine the levels of auditory processing (acoustic-phonetic-linguistic) in a systematic fashion. Four interrelated projects will examine these issues. Project 1 will investigate auditory processing at peripheral and central levels using behavioral, psychoacoustic, physiologic and electrophysiologic measures. Project 2 uses an event-related potential (ERP) mismatch negativity (MMN) to assess pre- attentive, automatic processing of acoustic events. Project 3 employs both behavioral and electrophysiological measures to determine whether the deficits seen in SLI are at the level of discrimination of acoustic-phonetic distinctions or at the level of categorization of these distinctions into language (i.e., phonemic categories). Project 4 extends the investigations from the acoustic/phonetic to the lexical (word) level processing using behavioral and electrophysiologic measures. Project 5 examines the effects of training or alteration of auditory input on spoken language. The study populations will be 1) children with specific language impairment; 2) children with history of otitis media with effusion that results in mild fluctuation hearing loss at a critical time in language acquisition; 3) children with congenital mild to moderatesevere cochlear (sensory hearing loss; 4) infants with "paradoxical" early auditory status findings (abnormal brainstem response in the presence of normal otoacoustic emissions); 5) bilingual children; and 6) normally developing children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL DYSREGULATION

STUDIES

OF

MIDDLE

EAR

PRESSURE

Principal Investigator & Institution: Swarts, J Douglas.; Children's Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001

Hosp

42

Otitis Media

Summary: Clinical and experimental evidences show that disruption of the mechanism for middle ear (ME) pressure regulation is associated with pathophysiological changes including the development of significant under- pressures and mucosal inflammation that if prolonged results in otitis media with effusion (OME). Adequate regulation of ME pressure requires that the intermittent transient openings of the Eustachian tube (ET) provide a sufficient quantity of gas to balance the net glasses associated with the gradient driven exchange between the ME and blood. Poor ET function causes ME under-pressures and OME by the hydrops ex vacuo mechanism, the validity of which has been convincingly demonstrated in experiments conducted under this program. Indeed, treatments for OME that bypass the ET to supply the ME with gas were shown in clinical trials to promote disease resolution. ET function tests in children and adults with concurrent diseases that predispose them to OME show changes in intraluminal congestion that present as a decreased efficiency of the muscular assisted mechanism of tubal dilation. Other studies in children "t risk" for OME and with concomitant OME, show a primary impairment of the active mechanism for tubal openings. However, the prognostic value of ET function tests with respect to disease course is limited, provoking controversy as to the role of ET dysfunction in the pathogenesis of OME. Recent studies conducted under this program show that the discordance between disease progression and test results may be explained by the failure of current test protocols to assess concurrently the functional demand placed upon the ET by the varying rates of transmucosal gas exchange. The overall objective of this project is to develop clinically applicable tests for ME pressure regulation that assess simultaneously these demand and supply functions. Also evaluated is the effect of measured test parameters associated with mucosal healing. Because histopathological studies cannot demonstrate an anatomic basis for poor ET function, new MRI imaging techniques will be used in an attempt to relate in vivo ET structure and function. The goals of this project are to develop a better understanding of ME pressure-dysregulation in the pathogenesis of OME, to evaluate the prognostic value of newly developed test protocols for assessing that function, to identify the underlying cause(s) of ET dysfunction, and to utilize this knowledge in suggesting new treatment strategies for OME. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL-HISTOPATHOLOGICAL CORRELATES OF OTITIS MEDIA Principal Investigator & Institution: Paparella, Michael M.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: COMPUTATIONAL INVESTIGATION OF EUSTACHIAN TUBE FUNCTION Principal Investigator & Institution: Ghadiali, Samir N.; Children's Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213

Hosp

Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The objective of this application is to investigate how the mechanical and anatomical (geometrical) structure of the Eustachian tube (ET) affects its ability to regulate Middle Ear (ME) pressure. Normally, this function is achieved by the intermittent opening of the ET due to the contraction of the surrounding

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musculature. Clinical and experimental studies have demonstrated that disruption of this opening mechanism results in one of the most common childhood diseases, otitis media with effusion (OME), and the associated hearing impairment. To obtain a fundamental understanding of the ET structure-function relationship, we propose to create a computational model that is capable of simulating both mechanical and anatomical variations. This model will be used to perform detailed simulations of ET opening phenomena during swallowing under various mechanical and anatomical conditions. As such, this work will elucidate how the interaction between mechanical and anatomical properties affects ET function. In addition, experimentally measured structural properties from normal adults will be incorporated into the model to obtain a better understanding of the "normal" ET structure-function relationship. The specific aims of this project are: 1) Develop a 2D computational model to investigate the influence of structural properties on ET opening phenomena during swallowing; 2) Develop and compare a 3D reconstructed mode of the ET with a 2D approximation to determine the importance of 3D geometrical variations; 3) Utilize the computational model to investigate and quantify ET opening phenomena in normal adults. The proposed work will elucidate how the mechanical and anatomical properties of the ET influence opening phenomena. In addition, we will establish normative data on the ET's mechanical and anatomical structure. This information is vital to the long term goal of this research which is to develop effective treatment strategies based upon the underlying structural deficiencies for persistent OME. Further, the results of the proposed research will provide the basic data which can be used as a comparative database for future studies that will quantify the ET structure-function relationship in OME patients, evaluate computationally various clinical therapies, and develop refined computational and/or experimental models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--BIOSTATISTICS Principal Investigator & Institution: Rockette, Howard E.; Professor and Chair; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--HUMAN SUBJECTS & BIOSTATISTICS FACILITY Principal Investigator & Institution: Le, Chap T.; Distinguished Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): We will form a Human Subjects and Biostatistics Core. The Biostatistics Component is the same Core Unit that has been collaborating with this Research Center over the last 21 years. The Human Subjects Component is new to the Otitis Media Research Center, with past services being incorporated in existing projects. The two components, Biostatistics and Human Subjects, could form two separate Cores; however, they both provide services in data management and support to help the investigators complete and enhance their existing aims and explore future research directions. By combining into one Core Unit we will also ensure that the various project databases will receive enough supervision from biostatisticians. To staff this combined core unit, we have assembled a team of highly qualified investigators. In

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Otitis Media

Biostatistics Dr. Le, Mr. Lindgren, and a graduate research assistant have expertise in the design of pilot studies, design and management of clinical trials and surveys, database development, data processing, and statistical analysis. In Human Subjects Dr. Daly, Ms. Knox, and a graduate research assistant will continue to provide services to yield data of consistently high quality for existing projects, enhancing the ability of these individual projects to complete their specific aims and explore new related aims. A unique feature of the Core will be the provision of pilot data for new projects drawing from databases and participants from previous OM studies. The mission of the Human Subjects and Biostatistics Core is to support and promote high quality otitis media research. This core is responsible for assisting the PIs in study design, data collection and processing, quality control, data storage and retrieval, and data analysis of all studies, so as to provide all investigators with a high level and broad range of expertise in data quality, management and data analysis. The key areas are quality control and standardization of data analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DECISION ANALYSIS OF OTITIS MEDIA VACCINATION STRATEGIES Principal Investigator & Institution: Lieu, Tracy A.; Associate Professor; Harvard Pilgrim Health Care, Inc. 93 Worcester St Wellesley, Ma 02481 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Background: Various candidate vaccines against otitis media are currently in development. These include new or improved vaccines against non-typeable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and respiratory syncytial virus. The ultimate success of otitis media vaccines will depend on their effectiveness and cost-effectiveness when implemented in large populations. Each of the possible vaccines and vaccination strategies poses a distinct set of tradeoffs in health benefits, risks, and costs. Research Plan and Specific Aims: We will develop a detailed decision analytic model to evaluate alternative otitis media vaccines and vaccination strategies for a hypothetical birth cohort of U.S. children. To complete this model, we will generate epidemiologic probabilities and costs by analyzing data from two ongoing cohort studies. We will assemble data from multiple additional sources and gather expert panel opinion where data are uncertain. The analysis will: 1) Compare the projected health benefits, health risks, and costs of alternative strategies for otitis media vaccination, including universal vaccination of infants between birth and 6 months, selective vaccination of children who are high-risk based on clinical history and/or sociodemographic factors, maternal immunization, and the status quo; 2) Define the sets of conditions under which otitis media vaccines are economically viable; and 3) Conduct sensitivity analyses to identify specific areas where further investment in research will yield information with maximum influence on future policy decisions. Projected Findings and Policy Implications: This study will provide population-based projections of the health and economic impact of alternative strategies for otitis media vaccination. The decision analytic model will yield information toward the optimal choices for current scientific inquiry, and will also provide a foundation for updated analyses as otitis media vaccines are further developed and tested. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS OF H. INFLUENZAE VIRULENCE IN OTITIS MEDIA Principal Investigator & Institution: Bakaletz, Lauren O.; Professor; Children's Research Institute 700 Children's Dr Columbus, Oh 43205 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from applicant's description) At the current time, we have a poor understanding of how NTHi cause otitis media in children. We hypothesize: (1) that there are as yet unidentified genes in NTHi which are important in the ability of this organism to cause otitis media; and (2) that there is a set of genes which are known but whose role in pathogenesis is uncertain or unsuspected. We propose using three complementary molecular strategies to identify these novel virulence-associated genes or to assign a role to those as yet undefined determinants: subtractive hybridization; differential fluorescence induction using promoter probe constructs; and signature tag mutagenesis. Genes unique to NTHi, genes differentially expressed in NTHi and/or genes obligatorily required at one or more stages of the infectious process will be identified by sequence determination. Some of the genes we identify in NTHi will have homology to genes present in the published strain H. influenzae Rd genome. Sequences with no homology to Rd genes but with homology to known virulence determinants of other organisms, or unique genes which have no homology to previously identified genes, will be cloned and sequenced. Isogenic mutants, deficient in newly identified putative virulence-associated determinants, and promoter probe constructs will be used in a battery of in vitro and in vivo biological assays to dissect the role of these determinants in disease. We will utilize a number of established systems for assessing NTHi adherence, colonization and bacterial cell uptake to initially analyze mutants for absence of these virulence- associated phenotypes. We will subsequently employ several chinchilla models of both frank disease induction as well as one of disease progression to more fully characterize the role of identified determinants in pathogenesis. Chinchilla models of active and passive protection will also ultimately be used to assess the relative efficacy of antibodies directed against selected newly identified antigens of interest in prevention of otitis media. The long term goals of this proposal are to gain an increased understanding of the pathogenic mechanisms operative in otitis media induced by NTHi. The identification of new potential vaccine candidates as well as novel targets for antimicrobial therapeutics could contribute significantly to the goal of developing more effective and accepted methods to both manage otitis media and ultimately prevent it. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT AND PLASTICITY IN NORMAL AND IMPAIRED EARS Principal Investigator & Institution: Hall, Joseph W.; Professor; Otolaryngology/Head & Neck Surgery; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-SEP-1986; Project End 31-AUG-2004 Summary: The long-term aim of this project is an understanding of auditory development in normal children and in specific clinical popultions of children. One major Study Area is the effect of otitis media on auditory development. The specific aim in this area is assessment of the hypothesis that children with a history of otitis media have particular impairment for the processing of speech under particular conditions: when binaural cues are available for masking release, and when the task is designed such that it is difficult to perceptually segregate the speech from masking interference.

46

Otitis Media

The second major Study Area assesses the nature of auditory processing deficiencies in children diagnosed with specific language impairment. One specific aim will be to evaluate the hypothesis that such listeners have explicit deficits in coding the temporal aspect of the signal. The competing hypothesis will be assessed that such children have a more general deficit in auditory processing based upon relatively subtle/difficult cues. A related aim will be to control for possible effects of hearing loss history among the children with specific language disorder. The third major Study Area will investigate developmental and basic mechanisms of binaural masking release. Basic experiments on adult listeners will address the question of whether binaural masking release depends upon selective temporal weighting of temporal epochs that are favorable for detection. A related developmental study in this area will investigate the finding that children have reduced MLDs for narrowband noise maskers even though their MLDs are adultlike for relatively wideband maskers. We will examine the hypothesis that children do not take advantage of the narrowband masker valley epochs containing the best signalto-noise ratios. In all Study Areas, most psychophysical or speech recognition methods will use three-alternative or four- alternative forced-choice testing with sound presentation over earphones. All phases of the project will include age-matched control listeners. Data will be analyzed using analysis of variance and correlation procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF A MIDDLE EAR BALLOON IMPLANT Principal Investigator & Institution: Merchant, Saumil N.; Associate Professor of Otology & Laryngo; Boston Medical Products, Inc. 117 Flanders Rd Westborough, Ma 01581 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-AUG-2004 Summary: (provided by applicant): Development of a new type of middle ear implant, a "middle ear balloon" is proposed. This implant is intended to restore hearing in nonaerated ears by creating and permanently maintaining an air or gas-filled space within the middle ear. Non-aerated middle ears resulting from eustachian tube dysfunction camonly occur in chronic otitis media (COM) and in otitis media with effusion (OME). The implant has significant potential as novel treatment for conductive hearing loss in patients with COM who have non-aerated ears, and in a subset of patients with OME when standard therapy has failed. A successful balloon implant must be easily fabricated, be biocompatible be easily compressible by sound vibrations, and must act as a physical barrier to fluid and gases. In Phase I, we successfully developed prototype balloon devices that meet these criteria. In Phase II, we propose to: 1) test long-term biocompatibility and safety using animal models; 2) assess long-term efficacy using laboratory-based testing; and 3) identify suitable technology for large scale manufacture. Completion of the proposed Phase II research should enable us to obtain an investigational device exemption from the FDA and to initiate prospective human clinical trials in follow-on, Phase III research. PROPOSED COMMERCIAL APPLICATION: The proposed balloon implant offers a novel method for treating conductive hearing loss due to non-aerated middle ears in chronic otitis media and some cases of otitis media with effusion. There is a large market potential for this implant, estimated at over 65,000 devices annually in the U.S. alone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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47

Project Title: DEVELOPMENTAL PHONOLOGICAL DISORDERS Principal Investigator & Institution: Shriberg, Lawrence D.; Professor; Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JUL-1988; Project End 30-JUN-2003 Summary: The development of diagnostic systems to assess and classify persons with communicative disorders, particularly etiologic systems leading to molecular genetics studies, is a key research target of NIDCD (National Strategic Research Plan, 1993). This research program is specifically concerned with these goals for the estimated 3 percent 8 percent (approximately 4.8 million) children in this country with speech disorders of unknown origin. The research plan for the next period has three specific aims: to validate a phenotype marker for a genetically transmitted subtype of child speech disorders, to cross-validate a descriptive-explanatory model relating otitis media with effusion (OME) and hearing loss from 6-18 months to speech-language deficits at ages 36, and to explicate acoustic-phonetic correlates of reduced intelligibility in children with histories of significant OME. A total of 15 data sets will use speech information from 2,773 children from clinical-research facilities in six states. Project I: Speech-Genetics Studies has three project strands: (a) an epidemiologic study to estimate the prevalence of speech delay in kindergarten children, providing liability estimates for behavioral and molecular genetics research; (b) cross-sectional studies to test the optimum phenotype marker for speech delay in genetics studies-a broad- domain (core verbal trait disorder) marker using measures of phonological processing (i.e., phonological awareness) or a narrow- domain marker based on alternative productive speech metrics; and (c) longitudinal studies to determine whether normalization of speech disorder is associated with familial aggregation, with implications for genetic versus environmental regulation. Collaborative molecular genetics studies at three sites will test the alternative phenotypes. Project II: Speech-Otitis Media Studies has five project strands: (a) statistical modeling studies to identify sources of variance in unintelligibility in relation to OME, hearing loss, and speech-language variables; (b) acoustic correlate studies to describe and explicate acoustic contrastivity features associated with OME and lowered intelligibility; (c) structural equation modeling studies to characterize how OME and hearing loss at 6-18 months moderate and mediate later speech delay; (d) case studies using auditory-perceptual and acoustic-phonetic methods to describe intelligibility differences in children with speech delays before, during, and after episodes of OME; and (e) longitudinal studies to determine the course of normalization from 3-6 years of intelligibility deficits associated with early recurrent OME. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ELECTROPHYSIOLOGICAL INDICES OF ACOUSTIC PROCESSING DEFICITS Principal Investigator & Institution: Vaughan, Herbert G.; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001 Summary: The overall goal of this project is to test the hypothesis that Specific Language Impairment (SLI) is associated with deficits in acoustic processing. To this end, the mismatch negativity (MMN) of event-related potentials will be used to assess a variety of basic capacities associated with pre-attentive, automatic processing of acoustic events. These capacities include: 1. detection of changes in intensity, frequency and stimulus duration; 2. identifying features of acoustic stimuli that are constant while other features

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Otitis Media

change; 3. determining that the order of two-tones pairs has changed; 4. determining that the serial order of three to five tones has changed; 5. forming an abstract rule as to the direction of change between the frequencies of two-tones pairs across a series of pairs (e.g., that they all rise in frequency from the first to the second tone), while the absolute frequencies of the tone pairs varies; 6. the duration of transient memory upon which the MMN relies. In addition, SLI and control subjects will receive training on the paradigm used in points 1-4 above which yields the poorest MMN to determine whether the MN will become larger in amplitude and/or shorter in latency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTROPHYSIOLOGICAL MANIFESTATIONS OF PHONETIC PROCESSING DEFICITS Principal Investigator & Institution: Kurtzberg, Diane; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001 Summary: For normal language acquisition, children must be able not only to discriminate fine-grained acoustic differences within the speech signal, but also must transform this information into phonological categories relevant to their language. It has been proposed that impairment of a child~s ability to discriminate acoustic-phonetic differences, particularly those stimuli that are brief and rapidly presented and/or acoustically similar; and/or to appropriately categorize this information into phonemic categories can result in disordered language development. Three groups will be studied: 1) children with specific language impairment (SLI) in whom peripheral hearing is entirely normal, but language development is impaired without general cognitive deficits; 2) children with histories of otitis media with effusion (OME), whose peripheral functioning is now normal, but who experienced episodes of mild, temporary hearing loss during the time of language acquisition; and 3) normall developing children, who will serve as controls. Behavioral and electrophysiologic measures will be employed to identify and characterize impaired phonological processing and to determine whether the deficit is due to difficulties in discrimination or to difficulties in identification of phonetic/phonemic information. A passive oddball paradigm to elicit mismatch negativity (MMN) will be used to index preattentive discrimination. Active discrimination and categorization tasks will be used to elicit attention-dependent eventrelated potentials. The spatiotemporal characteristics of these ERPs to phonetic contrasts will be identified in NL children and then will be employed to characterize the neural correlates of phonemic processing dysfunction in SLI children and those with histories of OME. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EUSTACHIAN TUBE FORM/FUNCTION IN CLEFT LIP AND PALATE Principal Investigator & Institution: Gungor, Anil; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Non-syndromic clefts of the lip and/or palate are among the most common malformations of the head and neck. Hearing loss and otitis media and effusion (OME) are common in cleft palate (CP patients because of poor Eustachian tube (ET) function resulting from hypoplasia and malpositioning of the palatal muscles, hypoelasticity of the ET cartilage and neuromuscular immaturity. One goal of palatal reconstruction is to establish more normal muscle vectors and

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attachments so as to improve tubal function and prevent future OME episodes. Unfortunately, that goal has not been realized because of a limited knowledge of the anatomical foundation for ET function. Recent methodological advances for evaluating ET function and for in vivo assessment of soft tissue anatomy hold much promise to address that deficiency. In the proposed study, quantitative magnetic resonance imaging (MRI) measurements of the ET and paratubal muscles in combination with measurement of ET function will be used to develop the form-function identity for the ET system in CP patients. Specifically, we will enroll 40 children aged 7-10 years with repaired, unilateral and bilateral complete CP (n+20/group) and with and without tympanostomy tubes for persistent OME (n=10/subgroup). Each child will have an MRI to define ET anatomy and a comprehensive battery of ET function tests to assess function. These data will be compared to those available for non-CP patients and analyzed for consistency with predictions that: 1) compared to age matched non-CP patients. CP patients have a hyperplastic ET cartilage, undeveloped paratubal muscles, aberrant origins and/or insertion for those muscles, greater ET compliance and poorer muscle-assisted ET opening: 2) the relative degrees of poor function and abnormal morphology are graded with the unilateral complete CP patients having lesser deficiencies than the bilateral complete CP patients: 3) the degree of functional impairment in these patients is directly related to the degree of anatomical deficiency, and 4) the anatomical deficiencies noted for CP patients with patent tympanostomy tubes are more extreme than those in the age-matched CP patients without a tympanostomy tube and no recent history of OME. If these predictions are valid, an early MRI study of CP infants be prognostic of the severity and longevity of ME disease and may serve to guide the type of palatal reconstruction for individual patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPRESSION OF SAP OPERON IN NTHI-INDUCED OTITIS MEDIA Principal Investigator & Institution: Mason, Kevin M.; Children's Research Institute 700 Children's Dr Columbus, Oh 43205 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Bacteria have evolved strategies to resist host defense mechanisms including resistance to antimicrobial peptides (APs). The sap (sensitivity to antimicrobial peptides) operon plays a significant role in this defense, as demonstrated by attenuation of sap operon mutants in animal models. The hypothesis of this proposal is that the sap operon plays a significant role in nontypeable Haemophilus influenzae (NTHI) survival in a chinchilla model of otitis media by maintaining resistance to APs in vivo and by up-regulating expression of specific AP resistance determinants. Expression of the sap operon during the disease course of otitis media or when exposed in vitro to chinchilla neutrophils or neutrophil granule extract will be analyzed by flow cytometry and histology. Mutations in the six genes of the NTHI sap operon will define the functional requirement for each gene in vivo. Finally, microarray analysis will be used to identify genes that determine resistance to APs as a result of sap operon expression. The data generated from these studies will significantly advance the field in understanding how NTHI adapt to the innate immune response in vivo in microenvironments encountered during disease progression and will identify novel virulence mechanisms resulting from sap operon expression that enable NTHI to survive and cause disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE DISCOVERY FOR PNEUMOCOCCAL OTITIS MEDIA Principal Investigator & Institution: Pettigrew, Melinda M.; Epidemiology and Public Health; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Otitis media (OM) is the most common bacterial infection in the United States among young children for which medical care is sought, and Streptococcus pneumoniae strains are the leading cause of bacterial OM. These gram-positive diplococci colonize the respiratory tract in up to 50% of healthy children and only cause disease under special circumstances. Recent genomic sequencing projects and advancements in molecular biology have resulted in the identification of numerous putative virulence factors. These factors have mainly been studied in the context of invasive pneumococcal diseases such as pneumonia, or have been studied in one or a few laboratory strains. While more virulence factors remain to be discovered, the new challenge is to identify which of these many factors warrant further study, to link these factors specifically to OM pathogenesis, and to estimate the relative importance of these virulence factors among the S. pneumoniae strains in circulation. This project is built on the observation that S. pneumoniae strains differ in their ability to cause disease, and that these differences are likely due to genetic differences between strains that extend beyond the polysaccharide capsule. The goal of this project is to identify genes associated with pneumococcal OM and to evaluate the relative frequency of pneumococcal virulence genes among a collection of isolates obtained from healthy children and children with clinical disease. A four step interdisciplinary approach utilizing techniques of molecular biology and epidemiology will include: 1. Selection of S. pneumoniae strains for genomic subtraction with the highest potential to identify genes associated with OM. 2. Identification of DNA sequences (sPCR fragments) unique to strains causing OM (tester strains) and absent in strains from healthy carriers (driver strains) using genomic subtraction. 3. Epidemiologic screening of a large collection of isolates from healthy children and children with OM, meningitis, pneumonia, or bacteremia using sPCR fragments. 4. Identification of genes associated with sPCR fragments important for OM pathogenesis and description of their biological and clinical characteristics. Discovery of additional factors involved in streptococcal OM will facilitate the development of new strategies for the control and prevention of this important disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC IMMUNIZATION AGAINST PNEUMOCOCCAL DISEASE Principal Investigator & Institution: Zeng, Mingtao; Microbiology and Immunology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Streptococcus pneumoniae is the most common bacterial cause of otitis media and acute respiratory infection and is estimated to result in over three million deaths in children every year worldwide from invasive diseases such as pneumonia, bacteremia, meningitis, and septicemia. The low efficacy of currently licensed pneumococcal polysaccharide vaccine has necessitated research into more efficient vaccines against pneumococcal disease. The long-term goal of this research is to develop a multi-component vaccine against pneumococcal disease, using genetically and antigenically conserved outer membrane proteins PspA, PsaA, and detoxified pneumolysin (PdB) from S. pneumoniae. Our hypothesis is that an effective pneumococcal vaccine should be composed of multiple conserved relevant antigens

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delivered preferably by a mucosal route in order to provide the best non-serotypedependent protection against S. pneumoniae infection. Intranasal and transcutaneous immunization with replication-incompetent adenoviral vectors have proved to be efficient and simple for immunization. This non-invasive vaccine delivery will undoubtedly enhance the compliance of a vaccination program. In this project, adenovirus and plasmid expression vectors encoding PspA, PsaA and PdB will be constructed. In order to obtain an optimal vaccination protocol, immunization regimens with different combinations of adenoviral vectors through the intranasal and transcutaneous delivery modes will be compared with the intramuscular injection of plasmid expression vectors. The specific aims of this project are: Specific Aim#1: To develop a replication-incompetent adenovirus-vectored vaccine against Streptococcus pneurnoniae. Specific Aim #2: To compare the mucosal and systemic immunity elicited by adenovirus-vectored vaccine through intranasal and transcutaneous administrations with that elicited by plasmid expression vectors through intramuscular injection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS /BIOLOGY OF M. CATARRHALIS LOS IN OTITIS MEDIA Principal Investigator & Institution: Campagnari, Anthony A.; Professor; Medicine; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Moraxella catarrhalis is a Gram-negative human pathogen, which predominantly causes middle ear infections and sinusitis in infants and children, and lower respiratory tract infections in adults. This organism is the third leading cause of otitis media and it is estimated that approximately 50% of children will become colonized by this bacterium in the first 6 months of life. Recurrent acute otitis media infections have also become prevalent resulting in potential hearing loss and subsequent developmental and learning problems as these children reach school age. Middle ear infections are very common and it is estimated that 80% of children under the age of 3 will experience at least one episode. There are also significant health care costs associated with treatment for otitis media and it has been determined that M. catarrhalis is responsible for approximately 3 to 4 million physician office visits annually. This estimate is considered conservative now that over 90% of M. catarrhalis clinical isolates produce b-lactamase. Together, these data have stimulated research efforts aimed at identifying specific virulence factors involved in colonization and infection. One prominent bacterial surface component implicated as a potential virulence factor, is the lipooligosaccharide (LOS). Structural studies show that M. catarrhalis LOS is similar to the LOS of other Gram-negative human pathogens, including Neisseris meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae. More importantly, these common LOS structures shared by M. catarrhalis and these prominent human mucosal pathogens have been implicated as virulence factors. Although M. catarrhalis express these LOS epitopes, there have been minimal studies describing the role of LOS in pathogenesis. In addition, there is currently no information available regarding the assembly and expression of this major surface glycolipid. In this proposal we will perform a comprehensive analysis of the genetics and biology of M. catarrhalis LOS. These studies will be instrumental to our understanding of the role of LOS in the pathogenesis of otitis media and should provide insight into new strategies designed to prevent this disease. We will test our hypotheses by the following specific aims: (1) Isolate and characterize of the genes involved in the biosynthesis and assembly of M. catarrhalis LOS. (2)Perform biologic studies to define the role for M. catarrhalis LOS in otitis media.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOMIC SEQUENCE OF AN OTITIS MEDIA ISOLATE OF NTHI Principal Investigator & Institution: Munson, Robert S.; Professor; Children's Research Institute 700 Children's Dr Columbus, Oh 43205 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): At the current time, we have a poor understanding of how nontypeable Haemophilus influenzae (NTHi) cause otitis media (OM) in children. We hypothesize: (1) that there are as yet unidentified genes in NTHi that are important in the ability of this organism to cause OM; and (2) that there is a set of genes that are known but whose role in pathogenesis is uncertain or unsuspected. Under current funding, we have begun an in-depth study of NTHi strain 86-028NP pathogenesis in the chinchilla models of OM. Specifically, we have employed differential fluorescence induction using promoter probe constructs; and signature tag mutagenesis to identify strain 86-028NP genes differentially expressed in NTHi and/or genes obligatorily required at one or more stages of the infectious process. We have also sequenced, to 3-fold coverage, the genome of NTHi strain 86-028NP. Some of the genes we identified in NTHi have homology to genes present in the published H. influenzae strain Rd genome. Sequences with no homology to Rd genes but with homology to known genes of other organisms, or unique genes which have no homology to previously identified genes, also have been identified. Although the genome information has been useful and informative, the assembly currently contains 576 contigs, many with regions of low coverage. The current contig data is available on our web site at www.microbial-pathogenesis.org. A global analysis of the current assembly indicates that the gene content and order are similar to that seen in strain Rd. A more detailed analysis reveals that there are a substantial number of genes not previously seen in the Pasteurellaceae and some regions where the gene content and order is different than seen in strain Rd. Thus, the current data suggest that the strain 86-028NP genome will contain a complex mosaic of Rd and non-Rd like features, features that may be important but are not completely discernable from the available data. The tremendous interest in vaccine development for NTHi disease, the increase in our understanding of the pathogenesis of NTHi disease and the knowledge that will be gained from the comparative genomics of different members of the Pasteurellaceae family makes it imperative that we have the complete genome sequence of at least one pathogenic NTHi strain. The National Institute on Deafness and Other Communication Disorders (NIDCD) has been extremely supportive of the functional studies of strain 86028NP (R01DC03915 from NIDCD/NIH, Lauren Bakaletz, PI) as well as the funding to obtain the 3-fold genome sequence coverage of this economically important pathogen (supplement to R0I DC03915 from NIDCD/NIH). We propose to close and annotate the genome of nontypeable H. influenzae strain 86-028. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLOBAL PATHOGENESIS

REGULATORY

INTERACTIONS

IN

BACTERIAL

Principal Investigator & Institution: Akerley, Brian J.; Microbiology and Immunology; Microbiology and Immunology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007

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Summary: (provided by applicant): Haemophilus influenzae efficiently and chronically colonizes the human nasopharyngeal mucosa, and is capable of causing invasive disease including otitis media, pneumonia, and, more rarely, meningitis. A number of factors involved in H. influenzae virulence have been identified in the pre-genomic era. Taking advantage of the genome sequence and the advent of new technologies, such as global expression profiling, we intend to advance understanding of critical virulence characteristics of this organism. Lipopolysaccharide (LPS) structural modifications are essential virulence determinants for H. influenzae. Using expression profiling with DNA microarrays, complemented by classical approaches, we have recently uncovered a previously unappreciated link between redox regulation and LPS modifications in H. influenzae. In addition, we have isolated a mariner transposon insertion mutation in H. influenzae that disrupts redox control over one such modification (addition of a phosphorylcholine epitope, termed ChoP, to the LPS) and also results in a pronounced colonization defect in an animal model of H. influenzae infection. These observations are of potential significance for in vivo modulation of the LPS structure by environmental signals. We propose to use such signaling and regulatory mutants generated in our laboratory to examine the role of redox signaling in controlling virulence genes in H. influenzae. Global genomic approaches we have developed for studies of H. influenzae will facilitate our analysis of how LPS modifications are modulated in response to environmental conditions. We will also determine whether other genes that play a role in pathogenesis are coregulated, inversely regulated, or constitutively transcribed under the varied redox conditions that affect LPS modification. We believe that these studies will provide important insights into the relationship between physiological adaptations to the host environment and the coordinated production of bacterial cell-surface structures critical for interactions with host cells or for evading the immune response. Specifically, we will: 1. Characterize the redox control mechanisms involved in the regulation of the ChoP cell surface LPS modification. 2. Investigate the role of signaling pathways in H. influenzae in the context of epithelial cell interactions and in a model of respiratory tract infection. 3. Examine coordinate regulation of virulence factors by redox signaling systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GUIDELINE DEVELOPMENT & IMPLEMENTATION - XML-BASED TOOLS Principal Investigator & Institution: Shiffman, Richard N.; Associate Director; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2005 Summary: A longstanding informatics challenge has been to develop effective and efficient mechanisms whereby valid medical knowledge can be applied in computer systems to support decision making by clinicians. The Guideline Elements Model (GEM) is a generic hierarchical representation of guideline knowledge that makes use of XML, a powerful technology for representing and manipulating electronic documents. The proposed activities are designed broadly to facilitate knowledge acquisition and representation for guideline-based decision support systems. Specific aims include: 1) To create tools that will facilitate transformation of published guidelines into computermediated guideline implementation systems. A generic process and software tools will be developed to translate GEM-encoded guidelines into systems that can improve the process of care. 2) To define the factors that influence the implementability of practice guidelines and to create an instrument that evaluates this construct. An international panel of experts on guideline implementation will help to define dimensions of

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implementability and participate in validation of the instrument. 3) To improve the quality and implementability of an evidence- based guideline produced by national specialty societies. Feedback regarding quality and implementability will be provided during the development of a guideline on management of acute otitis media by the American Academy of Pediatrics and the American Academy of Family Practice. 4) To extend and refine the GEM model to serve as a precise, comprehensive, and consistently applied ontology of guideline- related concepts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: H. INFLUENZAE GENES ASSOCIATED WITH ACUTE OTITIS MEDIA Principal Investigator & Institution: Gilsdorf, Janet R.; Professor of Pediatrics; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Acute otitis media results from a complex interplay of host defenses, environmental factors, and virulence characteristics of bacteria. Previous studies suggest that Haemophilus influenzae (Hi), an important cause of acute otitis media in children, possess unique genes important in the pathogenesis of this infection. In this project, we will identify potential virulence factors specific for Hi otitis media. Using a subtractive hybridization technique, we will identify DNA fragments present in Hi otitis media isolates and absent in Hi throat isolates. The subtracted DNA fragments will be cloned, sequenced and used to determine their prevalence among large panels of Hi strains grouped by various epidemiologic parameters. Our large collection of Hi strains will be screened for the otitis media associated genes using a gene detection-based microarray consisting of genomes of the Hi strains and associations among these genes as well as between these genes and epidemiologic factors established. The Specific Aims of this project are: 1. Characterize Hi isolated from middle ear effusions of children with acute otitis media and from nasopharyngeal throat specimens of children by biotype, serotype, b-lactamase production and genotype by pulsed field gel electrophoresis. 2. Identify candidate Hi otitis media associated genes through subtractive hybridization. 3. Describe associations among candidate Hi otitis media associated genes and between Hi otitis media associated genes and epidemiologic parameters, including site of isolation, geographic location, persistence of nasopharyngeal colonization and ability to be transmitted child to child, using a microarray of Hi genomic DNA from each strain in our collections. 4. Characterize the Hi otitis media associated genes by size, predicted function, and location in the Hi chromosome. Identification of unique Hi otitis media virulence factors will facilitate the development of novel approaches to the prevention and treatment of Hi otitis media. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: H. INFLUENZAE HMW ADHESION PROTEINS IN HOST IMMUNITY Principal Investigator & Institution: Barenkamp, Stephen J.; Professor; Pediatrics; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: Otitis media and other illnesses caused by nontypable Haemophilus influenzae (NTHI) remain significant health problems for children in this country and elsewhere in the world. The long-term objectives of this project are to identify those

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surface-exposed bacterial antigens of NTHI that are important in a protective host immune response and ultimately to address the question of whether or not a vaccine composed of such antigens would be effective in the prevention of disease. In previous work, we identified the HMW1/HMW2 family of proteins as major targets of the human serum antibody response following natural infection and colonization. Furthermore, we demonstrated a critical role for these proteins in adhesion of NTHI to eukaryotic cells. With respect to the potential of these proteins as vaccine candidates, we demonstrated that immunization of chinchillas with an HMW1/HMW2 mixture provided protection against experimental NTHI otitis media caused by the homologous strain. Finally, in our preliminary studies, we demonstrated that adult human serum antibodies specific for the HMW1/HMW2 family of proteins mediate opsonophagocytic activity against both homologous and heterologous strains. We propose to build on these earlier studies with the following specific aims. We will characterize the contribution of antibodies produced against the HMW1/HMW2- like proteins to the opsonophagocytic activity that develops in convalescent sera of children with acute NTHI otitis media. We will map those regions of the HMW1/HMW2-like proteins that express epitopes recognized by antibody capable of mediating opsonophagocytic activity against both homologous and heterologous strains. Finally, we will assess the ability of recombinant proteins that express epitopes recognized by antibodies mediating opsonophagocytic activity against homologous and heterologous strains to provide protection against disease in the chinchilla model of experimental NTHI otitis media. The knowledge gained from these studies will provide a clearer picture of the role of antibody to the HMW1/HMW2 proteins in host immunity and may move us closer to the goal of developing vaccines for prevention of nontypable Haemophilus influenzae otitis media and other diseases in young children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: H.INFLUENZAE HEMOGLOBIN/HEMOGLOBIN-HAPTOGLOBIN BINDING Principal Investigator & Institution: Stull, Terrence L.; Professor; Pediatrics; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2001; Project Start 01-DEC-1990; Project End 31-MAY-2006 Summary: Current vaccines against Haemophilus influenzae type b reduced the incidence of H. influenzae invasive diseases. However, nontypeable H. influenzae are a common cause of pneumonia and otitis media, which is associated with hearing loss and language deficits. H. influenzae has an absolute growth requiremnet for heme and the human body is its sole niche. Previously, we characterized a family of genes encoding proteins, Hgp, which bind human hemoglobin and the hemoglobinhaptoglobin complex. Mutation of all the hgp genes in a strain does not abrogate hemoglobin binding. We have identified a putative gene product encoding this residual hemoglobin utilization activity. Expression of Hgps is repressible by heme, but not by elemental iron. The upstream region of each gene lacks the Fur consensus site suggesting that the Fur repressor does not directly regulate the Hgps. We have isolated H. influenzae fur mutants and fur-independent mutants with altered hgp expression. Thus, regulation is more complex thatn the classic ferric uptake repressor system described for a wide range of bacterial species. Sequence analysis of Hgps reveals four highly conserved regions. Preliminary data about the complex regulation of hgp expression, localization of a binding region of HgpA, and the identification of conserved regions provide an opportunity to investigate the structure/function, gene regulation, and immunobiology of the Hgps. The current project will determine ligands bound by

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Hgp, identify binding sites, characterize the conserved regions, and determine the relative growth advantage of multiple Hgps in a strain. In addition, the role of fur and fur-independent elements in the regulation of Hgp will be examined. Finally characterization of the immunobiology of the Hgps will determine the protective capacity of antisera to the conserved regions of the Hgps in animal models of invasive and noninvasive disease. These experiments will provide insight into how heme acquisition is related to pathogenicity. These studies will lay the foundation for longterm studies focusing on prevention of all H. influenzae related disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HAEMOPHILUS HAP-MEDIATED MICROCOLONY FORMATION Principal Investigator & Institution: St Geme, Joseph W.; Associate Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Nontypable Haemophilus influenzae is a common cause of localized respiratory tract disease, including otitis media, sinusitis, bronchitis, and pneumonia. In addition, this organism causes serious systemic disease, such as meningitis, endocarditis, and septicemia. The initial step in the pathogenesis of nontypable H. influenzae disease involves colonization of the upper respiratory mucosa. We have identified an H. influenzae serine protease called Hap, which facilitates intimate interaction with epithelial cells and extracellular matrix proteins and also promotes bacterial aggregation and microcolony formation. Based on our in vitro results, we speculate that Hap plays an important role in the process of colonization. Hap belongs to the growing family of autotransporter proteins and is synthesized as a precursor protein with 3 functional domains, including an N-terminal signal sequence, an internal protease domain with adhesive activity (Haps), and a C-terminal outer membrane domain with translocator activity (HapBeta). Ultimately, Hap undergoes autoproteolytic cleavage, with extracellular release of Haps. In recent work, we demonstrated that Hap mediated adherence and microcolony formation are potentiated by a host protein called secretory leukocyteprotease inhibitor (SLPI). This protein is present in respiratory secretions and inhibits Hap autoproteolysis, resulting in accumulation of surface-associated Haps. In the present proposal, we will focus on Hapmediated adherence and microcolony formation. In Aim 1, we will solve the crystal structure of Haps and define the interactive surfaces involved in adherence and microcolony formation. In Aim 2, we will examine the ability of microcolonies to resist killing by cationic peptides, to evade macrophage phagocytosis, and to enhance persistence in the chinchilla otitis media model. In Aim 3, we will characterize the relationship between respiratory viral infection and Hap-mediated adherence and microcolony formation, concentrating on the role of SLPI. From a practical perspective, the proposed studies may facilitate efforts to develop novel strategies forthe treatment and prevention of H. influenzae disease. Perhaps more importantly, they may provide general insights into host-microbe relationships and expand our understanding of microbial biofilms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADHERENCE

HAEMOPHILUS--RAMIFICATIONS

OF

PILUS

MEDIATED

Principal Investigator & Institution: Krasan, Graham P.; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274

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Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Haemophilus influenzae is a pathogen that mediates a wide range of human disease including otitis media, sinusitis, and pneumonia often in association with an increased density of nasopharyngeal colonization. As is the case with other bacterial respiratory pathogens, an epidemiologically relevant risk factor for this process is prior injury of the respiratory mucosa associated with respiratory viral infections and environmental irritants (e.g. smoking). Colonization of the upper respiratory tract is an essential event in the pathogenesis of disease and is facilitated by bacterial adhesins that recognize specific receptors motifs on eukaryotic cells. The hemgglutinating pilus is perhaps the most well- studied H. influenzae adhesin and is expressed by both nontypable and serotypable strains. Our preliminary evidence suggests that this structure mediates adherence to damaged and extruding non-ciliated respiratory epithelium. A two-fold hypothesis to be pursued in this proposal is that this microbial virulence factor functions to compromised areas of the respiratory mucosa for subsequent pathogenic events and then further enhances the rupture of mucosal defenses by inducing respiratory epithelial cell apoptosis. Using the H. influenzae pilus as a model system, we will dissect the multiple roles in specific pilus receptor structure(s) on human respiratory epithelium by using piliated/non-piliated isogenic strains and microspherelinked pilus adhesin probes. We will then use these tools to characterize the dynamics of pilus receptor distribution on a re-organizing mucosal surface to determine whether this adhesion recognizes focal areas associated with its receptor can result in the manipulation of eukaryotic cell signal transduction mechanisms, increases the apoptotic index of epithelial cells, and disrupts the barrier of tight junctions between cells. The dynamics of respiratory colonization to surmount mucociliary clearance and cause disease. By focusing on this microbial virulence factor, we will be able to develop broadly applicable experimental systems that can be used to dissect the molecular details of host-pathogen interactions in respiratory disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEALTH OUTCOMES RELATED TO PRESCHOOLER'S SLEEP BEHAVIORS Principal Investigator & Institution: Davis, Katherine F.; Adult and Elder Health; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 14-SEP-2006 Summary: (provided by applicant): Despite support for the hypothesis that sleep loss impairs immune function, thus increasing susceptibility to infectious pathogens, human studies investigating the health outcomes associated with sleep loss are limited. This descriptive, correlational study will examine: (1) the general sleep behaviors, (2) the prevalence and frequency of sleep disturbances, and (3) the relationship between sleep disturbances and incidence of upper respiratory infections and otitis media in preschoolers attending daycare centers. Data will be collected once via a standardized sleep questionnaire and over a 12-week period using a prospective Illness Diary. The study design has proven feasible and the instruments have been pilot tested by the applicant. The results of this work will provide valuable data on the impact of sleep disturbances on the health of preschoolers attending daycare centers and may be applied to other populations also at high risk for infectious illnesses. Furthermore, this study will provide a foundation for future work developing nursing interventions to decrease the prevalence and incidence of sleep disturbances and ultimately lead to improvements in the health of children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEARING AND BALANCE IN LYSOSOMAL STORAGE DISEASES Principal Investigator & Institution: Hennig, Anne K.; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2004 Summary: (provided by applicant): Progressive hearing loss is a common feature of many lysosomal storage diseases (LSDs). These diseases are usually caused by an inherited deficiency in the activity of one of the hydrolases that function within the lysosomes. As a result, partially degraded substrate accumulates within lysosomes, causing a progressive impairment of cellular and organ function. The hearing loss is usually mixed; the conductive component can be accounted for by ossicle malformation, incomplete pneumatization and chronic otitis media, but the mechanisms underlying the sensorineural component are unknown. Furthermore, vestibular function has been examined only in patients with Fabry disease. Since effective therapies are now being developed for many of the LSDs, it is crucial to understand the otological manifestations of this group of diseases and the impact of these therapies on the underlying middle and inner ear defects. I propose to determine the extent and immediate cause(s) of hearing and vestibular dysfunction in six mouse models of different LSDs: MPS I/Hurler, MPS II/Hunter, MPS IIIB/Sanfilippo B, MPS VII/Sly, Fabry, and Niemann- Pick A/B. All of the human counterparts have associated hearing loss except Niemann-Pick A/B. Since these diseases all share impaired degradation of the carbohydrate component of cellsurface and extracellular macromolecules, the findings of this study will provide insights to potentially common mechanisms underlying the hearing and vestibular dysfunction in LSDs. In addition, virus- mediated gene transfer studies already in progress in MPS VII mice will be extended to examine the effects of therapy on the middle and inner ear. These studies will lay the groundwork for designing rational treatment therapies that will preserve or improve hearing and vestibular function. The specific aims of this application are: (1) to determine the extent and progression of hearing deficits in six mouse models of lysosomal storage diseases; (2) to determine the extent and progression of balance deficits in these mouse models; and (3) to determine the efficacy of gene therapy in correcting structural and functional deficits contributing to hearing and balance disturbances in MPS VII mice, a prototype LSD model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDENTIFICATION OF BIOCHEMICAL ABNORMALITIES IN PCD CILIA Principal Investigator & Institution: Ostrowski, Lawrence E.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: Primary ciliary dyskinesia (PCD) is an inherited disease which is characterized by various ultrastructural abnormalities in the cilia lining the respiratory tract. The defects in respiratory cilia are believed to result in impaired mucociliary clearance, and affected individuals suffer from recurrent respiratory infections, including rhinitis, sinusitis, bronchitis and pneumonia. In addition, many PCD patients also suffer from chronic otitis media, and males are frequently infertile. Currently, there is no curative treatment available for PCD, and the genetic basis of the disease is unknown. The long-term objectives of this proposal are to identify the genetic basis of PCD and to understand the pathogenesis of the disease. To achieve these goals, the following specific aims are proposed: 1: To identify protein(s) which are absent or altered in cilia isolated from cultured PCD cells. 2: To develop and characterize

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molecular and biochemical probes specific for the protein(s) which are altered in the cilia of PCD cells. 3: To determine if the gene coding for the protein(s) absent or altered in cilia from a PCD patient is mutated. Airway epithelial cells isolated from normal individuals and individuals with PCD will be cultured in vitro using techniques which allow the cells to differentiate into a well-ciliated epithelium. Cellular proteins will be radioactively labelled by the incorporation of labelled precursors and cilia will be isolated. The ciliary proteins will be compared using one- and two-dimensional polyacrylamide gel electrophoresis. Proteins which are altered or absent in the cilia from the PCD cells will be isolated and identified by mass-spectrometry. Antibodies and cDNA probes will be developed against the identified proteins. These probes will be used to determine if the gene coding for the protein is mutated, or if the protein appears altered in PCD cilia due to a mutation in another gene. These studies will identify defects in the cilia of PCD patients at the level of individual proteins. Ultimately, these studies will identify the mutation responsible for some cases of PCD, and will increase our understanding of how the mutation leads to disease. This information may lead to improvements in the diagnosis and therapy of this disease, including the possibility of gene therapy. Further studies of the role of these proteins in the assembly and function of cilia may also result in improved treatment for other air way diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFY AND DEVELOP MOUSE MODELS FOR OTITIS MEDIA Principal Investigator & Institution: Zheng, Qing Y.; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Otitis media (OM), one of the most common human diseases, is affected by multiple factors including Eustachian tube (ET), immune status, innate mucosal defense, pathogens, and genetic susceptibility. The mouse is the premier animal model for human disease research, and mouse models of OM represent powerful tools for advancing the understanding of OM. The broad, long-term objectives of this research are: to identify novel genes and/or novel functions of known genes that underlie OM susceptibility using a functional genomic and phenotyping driven approach and to develop innovative treatment strategies for human OM using genetic mouse models. The immediate goals are to identify, develop, and characterize genetic mouse models for OM by utilizing the unique mouse genetic and mutant resources at The Jackson Laboratory (TJL). TJL maintains more than 2,500 strains of mice, including inbred mice, mice with spontaneous mutations, and genetically engineered mice. Moreover, two large-scale mutagenesis programs at TJL are generating more than 1,000 mutagenized mice every month. Collectively, these valuable genetic resources offer an exceptional opportunity for the identification of new mouse models of OM. To provide the hearing research community with new models for the study of OM, we will: Aim 1. Develop techniques for diagnosis of OM in the mouse. We will focus on the adaptation of clinical tympanometry (tymp) and video-otoscopy (v-oto) techniques for the analysis of mice. We will test the sensitivity and specificity of these two tools in the mice by matched pathological studies of several potential or known genetic mouse models of OM. Aim 2. Test the hypothesis that heritable host traits influence OM development by identifying and characterizing genetic mouse models of OM. We will perform a twolevel screening of mice at TJL for OM susceptibilities and then carry out heritability testing to identify genetic mouse models. The screening strategy comprises a primary screen for elevated auditory brainstem response (ABR) thresholds and vestibular deficits (head tilting and circling), followed by a secondary screen of identified mice using our

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techniques developed in Aim 1 for the characterization of middle ear (ME) structure and function. Aim 3. Develop a pathogen-challenge methodology to evaluate genetic mouse models of OM identified in aim 2 by comparing their pathogen-challenge responses with those of controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE DAMPENING THE OMPS OF NON-TYPEABLE H. INFLUENZAE Principal Investigator & Institution: Nara, Peter L.; Exec. V.P. & Director of R & d; Biological Mimetics, Inc. 124 Byte Dr Frederick, Md 21702 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): One of the most challenging aspects of new vaccine development for viruses, bacteria and parasites is overcoming problems of antigenic variation. The development of vaccines against pathogens, which cause otitis media are being vigorously pursued by many groups, but is complicated in a significant way due to their antigenic diversity. Our incomplete understanding of the pathogenic mechanisms used by each of the three major bacterial species (nontypeable Haemophlius influenzae (NTHI), Streptococcus pneumoniae and Moraxella catarrhalis), their viral co-pathogens (Influenza, Rhinovirus, Adenovirus etc) and our inadequate understanding of the pediatric immune response during OM has presented multiple unique challenges. NTHI, a major bacterial pathogen of Otitis Media (OM) in children exhibits considerable strain-to-strain variation. The major outer membrane proteins (OMP) appear to be the major target of serum antibody and important targets of vaccine development. Immunological studies consistently show the antibody is directed to immunodominant, linear epitopes in surface loop structures of the OMPs which are strain dependent, undergo antigenic variation and leave the child unprotected against other circulating NTHI escape variants and strains. Detailed studies of two of these OMPs, the P2 and P5 proteins suggest that some regions of these OMPs exhibit less sequence variation. Thus using selected peptides from this result in the production of more broadly bactericidal antibody following immunization. Immunological and biophysical studies examining surface probability, hydrophilicity, flexibility, and antigenicity plots, strongly suggest that additional, more highly conserved regions of the protein, which are poorly immunogenic under natural conditions, could become immunogenic. Antigenic variation promoted through selective genetic instability is obviously a successful immunological strategy employed by many microbial pathogens. Coupling this to selective and focused immunodominance on the protein structure serves to prevent the immune system from recognizing other antigenic structures on the molecule. These "decoying" epitopes of the OMPs structure results in isolate-, strain- or serotype-specific antibody responses. The host immune system appears fixated on these more visible decoying epitopes at the cost of fully recognizing other conserved and protective epitopes within and between surface protein structures. The objective of this proposal is to further test the technology of immune dampening as a strategy to refocus the immune responses away from immunodominant, non-protective or serotyperestricted epitopes in P2 and P5, towards more broadly protective epitopes which (under natural conditions) are relatively less antigenic. The immune dampened and refocused P2 and P5 will be tested singly and in combination for their ability to induce cross strain protective antibody. Immune dampening technology provides for a new approach to circumventing the issues of antigenic variation and could help into the creation of more broadly protective vaccines against a variety of bacterial, viral and parasitic diseases of man and animals.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE MECHANISMS OF MIDDLE EAR DISEASE Principal Investigator & Institution: Skoner, David P.; Allegheny-Singer Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2003; Project Start 01-AUG-1982; Project End 31-DEC-2006 Summary: (provided by applicant): Otitis media (OM) is one of the most common diseases in children. Despite large societal expenditures, few treatments are efficacious and, consequently, a focus of intensive research is in the area of disease prevention. Viral upper respiratory infection (vURI) is a well-defined precondition for the development of OM and prevention of vURI by vaccination or immunoglobulin therapies was shown to reduce the population prevalence of OM. However, those treatments are risky and expensive rendering them ineffective for non-targeted application to the general population of infants and children. Because OM occurs in approximately 25% of vURIs and in only a subset of children, the ad hoc identification of those persons at "high risk" (by history, genotype, or phenotype) for OM during vURIs would significantly reduce the extent of over-treatment (i.e. treatment of patients with little risk of OM caused by vURI). Children can be classified by OM history into different risk categories and twin studies showed that susceptibility to OM has a high heritable component. We hypothesize that one component of OM heritability is the type of host response to a vURI. In earlier studies, we showed that: cytokines are synthesized and released during URIs; these cytokines correlate with illness expression, and cytokine production is modulated by genetic and environmental factors. In pilot studies, we reported a relationship between the interferon-? promoter genotype and OM incidence in infants with natural RSV infection and between an IL-6 promoter genotype and signs of illness in infants and adults with RSV infection. We propose a prospective study of young children, aged 18 months to 3 years followed through the typical RSV "season" for RSV infection and OM. All enrolled patients will be genotyped for a panel of cytokine response genes, and the influence of cytokine genotype on infection, illness scores/infection and OM/infection will be determined. The primary hypothesis is that cytokine genotype is predictive of illness expression and of OM incidence during a documented RSV infection in young children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE MECHANISMS OF MIDDLE EAR DISEASE Principal Investigator & Institution: Fireman, Philip; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001 Summary: This study explores the pathogenesis of otitis media with effusion (OME) and assesses the contribution of the various risk factors including infection, especially viral, allergy and immune competence. Experimental URI using rhinovirus (RV-39) and influenza A virus (IFA) were induced in normal susceptible human volunteers with and without a history of allergic rhinitis. Eustachian tube dysfunction was induced in 70 to 80% of infected subjects for both viruses with OME in 3% of RV-39 and 20% of IFA infected subjects. Enhanced serum IgE synthesis and WBC histamine release was documented in allergic but not in non-allergic subjects; whereas both groups had enhanced cytokines (IL-6, 8 and 10) in nasal secretions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE RESPONSES DURING MEASLES VIRUS INFECTION Principal Investigator & Institution: Griffin, Diane E.; Professor & Chair; Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-DEC-1985; Project End 31-DEC-2007 Summary: (provided by applicant): Measles remains a major cause of morbidity and mortality worldwide due to problems with delivery, acceptance and timing of measles immunization. An additional contributor to the continued failure of measles control may be the epidemic of human immunodeficiency virus (HIV) in developing countries, particularly sub-Saharan Africa, where many of the measles deaths occur. The primary complications of measles are pneumonia, otitis media, diarrhea and post-infectious encephalomyelitis and the effect of measles virus (MV) on the immune system is important in the development of these complications. Delayed type hypersensitivity skin test responses, natural killer cell activity and mitogen-induced proliferative responses are depressed and plasma IgE is increased for weeks after infection. At the same time, the immune response is effective in clearing virus from tissue and in establishing lifelong immunity to reinfection. Our studies of measles in the US and Peru have determined: (i) that monocytes, epithelial cells and endothelial cells are the primary sites of MV replication in vivo; (ii) that there is immune system activation during the period of "immune suppression"; and (iii) that type 2 cytokines are the predominant T cell cytokines expressed late in the response to MV. In vitro studies have shown that MV interaction with CD46 suppresses production of IL-12 by macrophages and that MV infection of B cells synergizes with IL-4 to induce IgE class switching. Recent studies in Zambian children have shown that concurrent HIV infection slows clearance of MV, that many children have baseline skewing of cytokine responses toward production of IL-5, and that measles transiently, but profoundly, suppresses HIV replication. To define the role of host immune responses during measles and the effect of concurrent HIV infection on these responses, we propose the fol]owing specific aims: 1. To determine the effects of MV infection on antigen presenting cells in vivo and in vitro and the consequences of these effects for the immune response. 2. To determine the role of CD8 T cells in MV clearance and the effect of concurrent HIV infection on this role. 3. To determine the roles of different CD4 and CD8 T cell populations in production of cytokines at various times during measles and the effect of concurrent HIV infection on these roles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNITY TO EPITOPES OF THE P6 PROTEIN OF H. INFLUENZAE Principal Investigator & Institution: Thanavala, Yasmin; Professor; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: Non-typeable Haemophilus influenzae (NTH1) is a common cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. Outer membrane protein P6 is a 16 kDa lipoprotein which is present in all strains of MTH1. The P6 protein is highly conserved among strains of NTH1, an important characteristics of a vaccine antigen. A large body of evidence from experimental animal models and from studies of the human immune response indicate that antibodies to P6 are protective against infection due to NTH1. In view of these observations, there is substantial interest in testing P6 as a vaccine to prevent infections caused by NTH. We have characterized the T cell response to P6 and

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the precise location of an immunodominant T cell epitope has been identified. This T cell epitope elicits P6 specific responses in mice of several different MHC Class II haplotypes. We have also demonstrated the ability of this T cell epitope to provide functional help to a B cell epitope in generating P6 specific antibodies. We now propose to study in vitro human T cell responses to P6 and synthetic peptides which span the entire sequence of the mature native protein. In an effort to elucidate the human antibody response to immunization with P6, SCID mice will be reconstituted with human peripheral blood lymphocytes, immunized with P6 antigens and the immun response will be characterized. Lymphocytes from normal adults and adults with COPD will be studied. The proposed studies will provide important information regarding human immune responses to the P6 protein and will further our knowledge regarding the potential of P6 as a vaccine antigen. Finally we will explore the potential of antigen delivery by the oral route and determine the ability of P6 and its peptides to generate both mucosal and systemic antibody responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF EARLY AUDITORY EXPERIENCE ON LATER AUDITORY FUNCTION Principal Investigator & Institution: Gravel, Judith; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001 Summary: The objective of this Project is to systematically study several groups of children who have known auditory processing disorders, or who are at high-risk for such deficits. Behavioral, psychoacoustic, physiologic and electrophysiologic measures will be used to examine hearing sensitivity, cochlear, brainstem and thalamocortical function, binaural processing abilities, and complex listening skills. We will examine children with: 1) early childhood histories of temporary conductive hearing impairment resulting from otitis media with effusion (OME); 2) congenital mild to moderate-severe sensory hearing loss; 3) specific language impairment (SLI); and 4) "paradoxical responses" on neonatal hearing screening measures. Our intent is to study whether: 1) the degree and persistence of the conductive hearing loss associated with OME during infancy and early childhood determines the extent of later peripheral and higher-order auditory dysfunction; 2) the higher-order auditory processing disabilities in children with early-onset cochlear impairments are accounted for by the degree and configuration of their peripheral sensory deficit; 3) children with SLI display higherorder auditory processing problems such as deficits in temporal resolution, binaural processing, and selective listening abilities; and finally, 4) whether infants identified in the neonatal period with abnormal brainstem responses in the presence of normal otoacoustic emissions (a ~paradox~) will persist with these indicators of auditory dysfunction through early childhood and, subsequently, whether they are at risk for communicative disorders. Since auditory deficits may affect one or more portions of the sensory pathway, the results obtained from our psychoacoustic, behavioral, physiologic and electrophysiologic probes of various levels of the system may prove valuable to our understanding the global effects of each of these unique auditory conditions on the child. The comprehensive delineation of auditory function may also serve as the basis for the development of intervention, education, and prevention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATORY MECHANISMS IN VIRAL OTITIS MEDIA Principal Investigator & Institution: Buchman, Craig A.; Associate Professor; Otolaryngology/Head & Neck Surgery; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: Acute otitis media (AOM) and viral upper respiratory tract infections (URIs) represent the two most common diseases affecting the human population, and account for substantial patient morbidity and health care costs. Epidemiological and experimental studies suggest that URIs play a causal role in the pathogenesis of AOM. Specifically, viruses can invade the middle ear (ME) space and invoke an inflammatory response that culminates in ME effusion (fluid) formation and consequent symptoms (pain, hearing loss). The molecular events responsible for the inflammatory response of the human ME following viral exposure have not been characterized. Studies using viral inoculation of nasal and tracheobronchial tissues suggest that the initiating inflammatory events are epithelium-mediated through local cytokine production. Since the ME normally does not contain aggregates of leukocytes, it is likely that the initiating events in viral otitis media are epithelium-mediated as well. The long-term goal of the present study is to investigate the ME mucosal response(s) to viral exposure in an effort to better understand the initiating events in AOM. Such knowledge will help develop new therapies for this significant disease. The goals of this project are to: (1) perform influenza A viral challenge experiments in the laboratory's normal ME epithelial cell culture system and measure expression of the interleukin (IL,)-1alpha, IL-1beta, IL-6, IL8, IL-10 and tumor necrosis factor (TNF)-alpha genes using reverse transcriptasepolymerase chain reaction (RT-PCR), in situ hybridization, and enzyme-linked immunoabsorbent assays (ELISA); (2) evaluate the same cytokine responses in ME epithelial cells derived from "otitis-prone" individuals; and (3) evaluate the efficacy of several potentially inhibitory substances in these models. The results of these experiments will provide a better understanding of the initiating events in viral otitis media and, hopefully, will lead to the development of novel therapies for this disease. Successful completion of this award by the principal investigator (PI) will provide the added research training and career development for future large-scale studies as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IRON ACQUISITION AND PNEUMOCOCCAL INFECTION Principal Investigator & Institution: Tai, Stanley S.; Howard University 2400 6Th St Nw Washington, Dc 20059 Timing: Fiscal Year 2001 Summary: Children under two years of age, the elderly, and individuals with underlying disease are to great risk of developing pneumococcal otitis media, septicemia, meningitis, and pneumonia. Antibiotic prophylaxis and vaccination are the two major methods to treat and prevent invasive pneumococcal infections. However, the success of antibiotic treatments has been limited by the recent isolation of penicillinor multi-drug resistant pneumococci. The current pneumococcal vaccine, a mixture of capsular polysaccharide of 23 most prevalent of possible 84 stereotypes, only elicits type-specific antibodies and can not provide protection against infection of other Streptococcus pneumoniae serotypes not used in the vaccine preparation. To control pneumococcal disease would require a new knowledge about the biology of S. pneumoniae. The long range goal of this investigation is to study how S. pneumoniae

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survives in infected animals where most of iron molecules are sequestered by ironbinding proteins, such as hemoglobin, transferrin, and lactoferrin. Iron limitation restricted the growth of S. pneumoniae and the limited growth could be restored by the addition of hemin or hemoglobin. Pneumococcal cells have a great ability to bind hemin. Several hemin binding proteins have been identified in the cell lysate of S. pneumoniae with the major species migrated as a molecular mass of 43 kDa. The specific aims of this proposal are employing genetic and immunological methods to seek answers to the following question: 1). What is the genetic determinant of 43-kDa hemin binding protein? 2). What roles does 43-kDa HBP play in the hemin acquisition of S. pneumoniae? 3) What roles does 43-kDa HBP play in S. pneumoniae infection in experimental animals? Results generated from the proposed studies not only will provide us with basic information about the iron acquisition of S. pneumoniae, but will allow us to gain insight into the pathogenic mechanism of S. pneumoniae disease. The knowledge obtained in this study will have practical applications as well in designing effective therapeutic strategy and agents for the control of pneumococcal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG TERM SEQUELAE OF OTITIS MEDIA Principal Investigator & Institution: Hunter, Lisa L.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MAST CELLS AND INNATE IMMUNITY IN OTITIS MEDIA Principal Investigator & Institution: Wasserman, Stephen I.; Professor and Chairman; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Otitis media is a major health problem causing substantial morbidity and resulting in substantial health care expenditures. The causes and treatment of this disorder remain incompletely understood. Eustachian tube obstruction, viral and subsequent bacterial infection and immunity have each been suggested to contribute to the etiopathophysiology of this disorder. Recent work in our laboratories has indicated that concurrent mast cell activation and bacterial infection can synergistically interact to induce strong inflammatory changes in the middle ear. These preliminary data, as well as prior research in the middle ear and other systems, suggest that the mast cell may play an important role in the innate and cognate defense of the middle ear, and may also contribute to otitis media pathogenesis. In this proposal Drs. S. Wasserman, A. Ryan and D. Broide propose a series of integrated experiments employing genetically modified mice to validate this hypothesis and to elucidate the mechanism(s) by which this synergistic interaction occurs. Aim 1 of this proposal will define the synergistic interaction utilizing mast cell deficient mice, with and without, reconstitution of their middle ear mast cells. Aim 2 will examine the mechanisms by which bacterial products enhance mast cell mediated synergistic inflammation by exploring the Toll-like receptor (TLR) pathways of mast cells. In these experiments TLR 2, 4, and 9 deficient mast cells will be used to re-constitute middle ear mast cell populations of mast cell deficient mice and the effect of bacterial/ mast cell interactions defined. MyD88 deficient mice, defective in all TLR signaling will be used to define

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potential redundancies in these responses. Aim 3 will re-constitute middle ear mast cells with mast cell populations obtained from mice which are deficient in one or more mast cell mediators including histamine, leukotriene and tumor necrosis factor alpha to define the mediator(s) responsible for mast cell enhancement of inflammation induced in the presence of bacteria. Aim 4 will elucidate the leukocyte/endothelial mechanisms by which mast cell] bacterial interactions enhance inflammation, by direct observations of leukocyte behavior in genetically modified animals. Together these studies will expand our understanding of the role of mast cells in otitis media and may identify new targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATERNAL IMMUNIZATION TO PREVENT INFANT OTITIS MEDIA Principal Investigator & Institution: Ferrieri, Patricia; Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Vaccine strategies to prevent childhood otitis media (OM) are being sought due to its major public health impact and the troubling increase in antibiotic resistant bacteria. The pneumococcus bacteria is a prime target for vaccine prevention. Maternal immunization is a strategy designed to prevent early infant OM, since it is one of the greatest risk determinants for recurrent and chronic OM. A recently licensed 7-valent pneumococcal conjugate vaccine (PCV7) is now given routinely to all infants beginning at age 2 months. This vaccine is highly protective against invasive pneumococcal disease after 7 months of age, has modest (6-9%) protection against all OM episodes between 7 and 24 months, and a 57% reduction in vaccine-type pneumococcal AOM. But it does not significantly reduce OM before 7 months. Thus, there remains a potentially important role for maternal pneumococcal immunization to prevent pneumococcal AOM in the first 6 months of life. Thus, it is important to test the hypothesis that maternal pneumococcal immunization during pregnancy does not produce immune interference in the infant, impairing response to the infant vaccine, before proceeding with a maternal vaccine OM efficacy trial. This Phase I/II trial will enroll 154 pregnant women and follow subjects and their infants to age 13 months. Primary aims are: (1) to determine if infants of women immunized with 9-valent PCV (PCV9) and infants of control women who receive placebo during the third trimester of pregnancy have equivalent anti-capsular polysaccharide (PS) IgG antibody responses to PCV7 measured one month after the third vaccine injection at 6 months of age, and (2) to compare local and systemic adverse events among women immunized with PCV9 or placebo. We will also investigate the hypotheses that (1) maternal immunization does not interfere with the infant's antibody subclass and pneumococcal opsonic responses to the primary PCV7 vaccine series or to booster PCV7 immunization at 12 months, (2) pregnant women have a significant antibody response to PCV9 vaccine compared to placebo vaccine and increased antibody persists 13 months after delivery, (3) anti-PS IgG and secretory IgA antibodies are present in the milk of immunized lactating women, and (4) maternal immunization does not interfere with the infants' antibody response to H. influenzae type b conjugate and diphtheria toxoid vaccines. Transplacental anti-PS IgG antibody transfer, the natural decline of two anti-PS antibodies against PS antigens in the maternal but not the infant vaccine, and the natural production of one anti-PS antibody not in either vaccine will be measured. The trial has enrolled and randomized 87 subjects to date with continuous, steady subject accrual since November 2000. Results of this trial will have a profound impact on the broad field

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of maternal immunization to prevent early infant disease caused by a variety of infant bacterial and viral pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF ACTION OF ANTIBODY TO PSPA Principal Investigator & Institution: Briles, David E.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-AUG-1984; Project End 31-OCT-2007 Summary: (provided by applicant): Streptococcus pneumoniae is one of the largest causes of death by infectious disease of the elderly worldwide. It is also one of the greatest causes of death among very young children in developing countries. Although the polysaccharide-protein conjugate vaccine is effective at protecting children from bacteremia and sepsis, protection is restricted to the included capsular types. The vaccine is only partially protective against otitis media and its potential for herd immunity is limited. Moreover, the conjugate vaccine is more than 100-fold too expensive for widespread use in the developing world. One way to improve this vaccine, or possibly replace it, would be to use protection-eliciting cross-reactive proteins of pneumococci. Several such proteins have been identified, and one, PspA, has reached clinical trials. PspA is required for full virulence of pneumococci in mice and antibodies to it are protective against sepsis, pneumonia, and carriage. Antibody to PspA can enhance the clearance of pneumococci from the blood of infected animals, and it appears to be able to increase complement deposition on the pneumococcal surface in vitro. Antibodies to PspA promote the attachment of pneumococci to phagocytes, but have not been found to be opsonic (even in the presence of complement) for phagocytosis and killing in vitro. To obtain a better understanding of how antibodies to PspA promote protection in vivo, we will examine several of their known biologic effects in detail. Our investigations will include in vitro conditions that are as close as possible to those in vivo. Investigations of a panel of protective and non-protective monoclonal antibodies, all of which will react with native PspA, will allow us to determine which biologic assays are relevant to in vivo protection. We will also map the epitopes that elicited the monoclonal antibodies. Identification of the in vivo mechanism by which antibody to PspA protects should enable development of a valid surrogate assay for protection, and should improve our understanding of pneumococcal disease. Our analyses of the protection-eliciting and non-protection-eliciting epitopes on PspA should make it possible to design even better PspA vaccines in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF TISSUE DESTRUCTION IN CHOLESTEATOMA Principal Investigator & Institution: Faddis, Brian T.; Otolaryngology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Cholesteatomas are epithelial tumor-like growths that arise from the tympanic membrane, typically as a sequela of chronic otitis media. The progressive nature of this lesion commonly results in the destruction of middle and inner ear structures via osteoclastic bone resorption. This destruction leads to hearing loss, vestibular dysfunction and intracranial complications. Current management of this disease is limited to surgical eradication, which must often be repeated. Chronic infection is another hallmark of the cholesteatoma and we have therefore been interested in the inflammatory signaling pathways that lead to osteoclast activation. We

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recently established a role for nitric oxide synthase 1 (NOS1 or neuronal NOS) in osteoclast activation. We now wish to explore this role further by identifying the mechanisms by which NOS1 is activated and the endogenous modulators that keep nitric oxide production in check. To this end, we have outlined the following specific aims. Specific Aim 1: To localize the cellular source(s) of NOSl that mediate osteoclast activity and to also localize potential endogenous modulators of NOSl. Specific Aim 2: To identify the mechanism of activation for NOSl and assess the efficiency by which various modulators can control nitric oxide production and ultimately the bone resorbing activity of osteoclasts in models of cholesteatoma. Neurons control NOSl activation by functionally linking it to the NMDA type of glutamate receptor. Interestingly, osteoclasts also have functional glutamate receptors, including the NMDA subtype, but their function is not well understood. Further, glutamate receptor antagonists inhibit the ability of the osteoclast to seal to the bone, a prerequisite to resorption activity. Osteoclasts from mice with targeted deletions of the NOS1 gene exhibit a similar phenotype. This coincidence offers intriguing evidence that these two observations are related and that osteoclasts may use the same mechanisms that neurons do to modulate NOS1 activation. These studies offer important insight into the control of osteoclast activity in cholesteatoma and may lead to the development of pharmacologic interventions that would replace the need for surgery in the treatment of this debilitating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MIDDLE STIMULATION

EAR

EPITHELIAL

RESPONSE

TO

CYTOKINE

Principal Investigator & Institution: Kerschner, Joseph E.; Assistant Professor; Otolaryngology and Commun Scis; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2006 Summary: (from applicant's abstract): Otitis media is the most common diagnosis in pediatric patients who visit physicians for illness in the United States. Despite the prevalence of otitis media, its potential for morbidity, the enormous health care expenditures resulting from its treatment and the increasing therapeutic challenges imposed by antimicrobial resistance, much is still unknown about the cellular and molecular immunologic and inflammatory events in this disease process. Middle car epithelium is known to play a significant role in the pathophysiology of otitis media through a cytokine mediated inflammatory response. Recent advances in cell culture techniques have enabled investigations of middle ear epithelium in culture and provide a mechanism to further our understanding of the cellular and molecular events in otitis media. The goals of this project are to test the hypothesis that cultured middle ear epithelial cells (MEEC) exposed to the inflammatory cytokines tumor necrosis factoralpha. (TNF-alpha), interleukin- 1 beta (IL- 1 beta), interleukin-6 (IL- 6) and interleukin-8 (IL-8) will exhibit changes in: 1) mucoglycoprotein secretion (MGP), 2) mucin gene expression and 3) morphology. Using cell and molecular biology techniques, differences in epithelial response to this array of inflammatory cytokines will be compared and the ability to block the specific changes brought about by these cytokines by the use of cytokine inhibitors will be examined. Post-receptor signal transduction of TNF-alpha, IL- 1 beta, IL-6 and IL-8 in regards to MEEC MGP secretion will also be examined. Understanding the cellular and molecular events involved in cytokine-middle ear epithelial interactions, MGP production, mucin gene expression and signaling pathways

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will potentially allow for novel and efficacious treatments for otitis media through modulation of the cytokine pathway and MGP production by middle ear epithelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MIDDLE EAR RESPONSE IN SEROUS OTITIS MEDIA Principal Investigator & Institution: Ryan, Allen F.; Professor of Surgery/Orolaryugology; Surgery; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: Otitis media is one of the largest public health problems of young children. Otitis media is thought to be a multifactorial condition that can result from a variety of inciting events. However, once initiated, otitis media often converges ona final common pathway of inflammation, effusion and tissue hyperplasia that in turn can produce temporary and even permanent hearing loss. Upon resolution of otitis media the hyperplastic middle ear mucosa can recover to a condition at or close to its original structure, although permanent changes including fibrosis and osteoneogenesis sometimes occur. In the previous period of support, we identified several growth factors that can contribute to mucosal hyperplasia. In the current application, we propose to study mechanisms that control tissue hyperplasia and recovery of normal mucosal structure in the middle ear. We will identify intracellular pathways that are activated in middle ear cells by growth factors, and determine whether inhibition of these pathways can reduce tissue hyperplasia during otitis media. We also propose to identify pathways controlling cell loss during recovery of the middle ear mucosa. Finally, we will determine whether stimulation or inhibition of activity in these pathways affects recovery from otitis media. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR ANALYSIS OF PATHOGENS IN OTITIS MEDIA BY PCR Principal Investigator & Institution: Ehrlich, Garth D.; Executive Director; AlleghenySinger Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2001; Project Start 01-DEC-1993; Project End 28-FEB-2003 Summary: (Adapted from the Applicant's Abstract) The proposal by Ehrlich and colleagues, "Molecular Analysis of Pathogens in Otitis Media by PCR," is a nonoverlapping continuation research application. The investigations planned will attempt to capitalize on and extend this group's findings dealing with infectious agents in otitis media (OM) currently funded as 5R01 DC02148-03 (Ehrlich), expiration date 11/30/97. Ehrlich's group has documented the presence of bacterial DNA and H. influenzae transcripts in culture-negative, otitis media with effusions (OME). This demonstration is a departure from one theory regarding the etiology of effusion in OM which holds that bacterial products, but not live bacteria, are responsible for causing the effusion. An experimental chinchilla animal model was developed and supported the PCR-based findings and suggested that antibiotic-treated bacteria may persist in a culture-sterile, but PCR-positive state for weeks. This continuing application will concentrate on the molecular biology of H. influenzae and factors which may lead to the development of OME. The central hypothesis which will be explored is whether OME is initiated and maintained by the establishment of biofilms. Biofilms are networks of adherent, or sessile, bacteria distinct from free-floating, or planktonic, forms. Biofilms have been implicated in causing contamination of implantable devices, "sterile" arthritis, and

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prostatitis. Biofilm formation results from the coordinated expression of sets of genes that are induced upon bacterial attachment. Once formed, multiple species can live in specific microenvironments protected from the external environment and display extraordinary tolerance to antibiotics. This tolerance is primarily attributable to the reduced metabolic activity and lowered rates of cell division of sessile bacteria when compared to planktonic forms. To test these hypotheses the researchers will compare, through differential gene expression, the metabolic activity of free-floating bacteria, biofilm bacteria, and viable, culture-negative organisms from middle-ear effusions. To further characterize the transcriptionally active, effusion-derived H. influenzae, pulse chase experiments using RIPAs will be employed to evaluate levels of protein synthesis in the animal OM model. The focus will also be directed to other infectious agents that have been implicated in OME, including M. catarrhalis and S. pneumoniae, and OME will be assessed for the presence of the corresponding bacterial mRNA species using RTPCR. In a second series of experiments, the sterile OME-derived H. influenzae mRNAs will be screened for possible transcripts encoding inflammatory mediators. In a third series of experiments, attempts will be made to characterize the genes involved in H. influenzae biofilm formation and compared with the established biofilm-forming agent P. aeruginosa. A combined final series of experiments will attempt to determine the mechanism(s) that regulate or trigger the formation of biofilms and to correlate different models of mutational2 induction with the consequences of antibiotic therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCOSAL DEFENSE BY IGA AGAINST S PNEUMONIAE Principal Investigator & Institution: Janoff, Edward N.; Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (adapted from the investigator's abstract): Streptococcus pneumoniae is a common invasive mucosal pathogen. Local and systemic manifestations range from asymptomatic colonization, to sinusitis and otitis media, to community-acquired pneumonia, bacteremia, and meningitis, resulting in up to 40,0000 deaths/year in the US alone. The local host and bacterial factors that determine whether S. pneumoniae causes no disease, mucosal disease, or invasive disease are not well-characterized. We propose to characterize the mechanisms of control of pneumococcal infections operative at the initial steps in their pathogenesis from nasopharyngeal colonization to aspiration into upper respiratory mucosae and alveoli, prior to alveolar injury and invasion into tissue and blood. We have shown that IgA reactive with pneumococcal capsular polysaccharide (PPS) mediates killing by neutrophils by both complement-dependent and -independent conditions. IgA and IgG may both contribute to defense of the lower respiratory tract by initiating killing by macrophages and neutrophils and by inhibiting adherence to epithelial cells. We will characterize the molecular and biochemical features of PPS-specific Ig which determine their functional role, their effective interactions with local phagocytic cells, as well as the adaptive mechanisms of the organism which may subvert these protective mechanisms. Hypotheses: (1) Molecular and biochemical characteristics of capsule-specific IgA and IgG (e.g., mutation rates of immunoglobulin genes (VH), momeric, polymeric, and secretory structure of IgA, avidity, and pattern of IgA glycosylation) determine their functional efficiency to inhibit adherence and mediate killing by phagocytes. (2) Bacterial virulence factors (e.g., IgA1 protease, choline-binding protein A, and phase variation) subvert the ability of PPSspecific IgA to control S. pneumoniae. (3) The local host environment (e.g., complement, C-reactive protein) determines the phagocytes' ability of IgA and IgG to initiate killing

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of S. pneumoniae. The specific objectives of this proposal are designed to illuminate the unique features of the local host-pathogen interaction and defense against these extremely common and serious mucosal infections with S. pneumoniae in children and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW TREATMENT FOR INFLAMMATION IN MIDDLE EAR INFECTIONS Principal Investigator & Institution: Kurtz, Stephen E.; Targeted Gene Delivery, Inc. 2611 Sw 3Rd Ave, Ste 200 Portland, or 97201 Timing: Fiscal Year 2003; Project Start 15-DEC-2002; Project End 14-JUN-2003 Summary: (provided by applicant): Otitis media with effusion (OME) is one of the most prevalent inflammatory diseases in the pediatric population, and is associated with pain and hearing loss. OME is characterized by release of inflammatory mediators and enzymes such as pro-inflammatory cytokines, cellular infiltration into the middle ear, and secretion of a mucin-rich effusion. In the majority of cases, inflammation and resulting fluid accumulation are initially triggered by stimulation of host immune cells with specific bacterial products, such as end toxin. These stimulatory products are found both on intact viable bacteria and bacterial debris that is present after bacterial death. Currently, antibiotics are used almost exclusively for treatment of otiUs media, however antibiotic therapy only kills the bacteria and does not specifically target the inflammation and accumulation of fluid in the middle ear that irresponsible for the pain and diminished hearing seen in OME. The goal of this proposal will be to test the feasibility of a novel therapy to minimize or resolve the inflammation and result in accumulation of middle ear fluid, and prevent the hearing loss in OME. Our strategy will be to block at the initiating stage the intracellular activation that results from the interaction of bacterial products with host immune cells within the middle ear leading to inflammation and the clinical complications of OME. This proposal will establish conditions for inhibiting the cellular activation and inflammation induced both by specific bacterial products and cell extracts from killed whole bacteria. Once these conditions have been defined in vitro (Specific aim #1), the in vivo effectiveness of this therapeutic approach to minimize inflammation will be examined by assessing middle ear pathology, middle ear fluid accumulation, and prevention of hearing loss in an in vivo model of OME induced by injection of viable bacteria (specific aim #2). We speculates that the most efficient management of OME will involve a combination of antibiotics and a treatment specific for bacterial-induced inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NON-SURGICAL DEVICE FOR TREATMENT OF MIDDLE EAR EFFUSION Principal Investigator & Institution: Arick, Daniel S.; Arisil Instruments, Inc. 450 Clinton St New York, Ny 11231 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2003 Summary: (provided by applicant) The purpose of this study is to test the efficacy of a portable, automated, modified Politzer device for the nonsurgical management of middle-ear effusion in children (4-11 years of age). The objectives of this study are to determine whether the change in average air-bone gap and tympanometric peak pressure from the final pre-test to the post-test is greater for the experimental subjects who receive treatment with the device as compared with the control subjects. Subjects

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with middle-ear effusion will be randomly assigned to the experimental (n=59) and control groups (n=59). Each experimental subject will receive twice-daily treatment (administered by the guardian) with a portable, automated, modified Politzer apparatus over a period of 7 weeks. Post-testing (audiologic and otolaryngologic evaluations) will occur three weeks after the period encompassed by the treatment. The significance of this study will have far-reaching benefit in terms of a reduction of the need for surgical treatment for middle-ear efThsion. with resultant avoidance of possible adverse sequellae, and substantial reduction of cost of management from approximately $2,000 for surgical treatment to approximately $10 for nonsurgical management. PROPOSED COMMERCIAL APPLICATIONS: If the clinical trial proves to be successful, there will be national and international interest. Although the custom-made device costs $325 including product liability, when commercially produced, it will cost about $5.00. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OTITIS MEDIA AND LANGUAGE LEARNING SEQUELAE Principal Investigator & Institution: Roberts, Joanne E.; Professor; Otolaryngology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 13-SEP-2001; Project End 12-SEP-2002 Summary: (provided by applicant): After three decades of research, controversy continues on whether otitis media, one of the most common illnesses in early childhood, causes later developmental sequelae. Several recent studies and evidencebased reports examining the linkages of otitis media, hearing, and later speech, language, and learning have provided new information concerning this controversy. The focus of this research conference (Otitis Media, Hearing, and Language Learning Sequelae) is to use an evidence-based medicine model to: a) review current research on the effects of otitis media on children's hearing and development (i.e., speech, language, cognition, behavior, and academic achievement); b) define gaps in this research; and c) identify future directions for research, including study designs, populations, measures, and statistical methods. The conference target audience is scientists and practitioners from multiple disciplines, including speech-language pathologists, audiologists, developmental and cognitive psychologists, pediatricians, family physicians, and otolaryngologists. This interdisciplinary meeting will increase communication among the participants, foster the development of partnerships, and encourage future research. The conference will begin with a presentation discussing otitis media developmental sequelae as a health care concern, using an evidence- based medicine model. Next, previous research and ongoing prospective studies of otitis media and hearing, speech, language, and academic sequelae will be presented. Following each of these presentations, a panel will discuss and synthesize the research presented, identify gaps in the research, and define future directions. The speakers will be leading otitis media, hearing, and developmental researchers, who are conducting longitudinal studies. Funds are requested for travel and support for invited speakers, conference administration, publicity, and dissemination of the results. This conference will provide an important forum for researchers and practitioners to synthesize the results of research on otitis media, hearing, and language learning sequelae and will define an agenda for otitis media developmental research in the 21st century. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OTITIS MEDIA BEHAVIOR AND ATTENTION IN DAYCARE Principal Investigator & Institution: Frank, Thomas A.; Human Development and Family Studies; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 15-AUG-1996; Project End 31-JUL-2003 Summary: This research project will test hypotheses about the effects of otitis media (middle ear effusion) on young children's language, attention, and social behavior. Based on the findings from the previous grant, a Cumulative Risk Model will be tested to determine the influence of risk/protective factors (moderators) on whether otitis media and the accompanying hearing loss has negative outcomes for 200 children followed from infancy to 3 years of age in daycare. Environmental influences in the home and in the daycare will be measured carefully to understand whether these environments buffer children against the negative effects of otitis media or actually exacerbate them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OTITIS MEDIA CORE CENTER Principal Investigator & Institution: Daly, Kathleen A.; Associate Professor Sr. Research Assista; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Otitis media is among the most common childhood diseases, and otitis media sequelae are frequent in adults. A multidisciplinary team of basic and clinical scientists has led otitis media research at the University of Minnesota since 1978, when the University's Otitis Media Research Center (OMRC) was formed. The OMRC mission is to create a collaborative environment for interdisciplinary research that stimulates advancement in understanding otitis media pathogenesis, to inspire new developments in diagnostic technology, treatment and prevention modalities, and to generate and disseminate fundamental and clinical knowledge, thereby, enhancing patient care. The Otitis Media Core Center will support 16 currently NIH-funded base research projects (12 NIDCD-funded) and an additional two recently submitted projects. OMRC research is focused in basic molecular, cellular, microbial, immunological, animal modeling, population science, and clinical studies. Research productivity is demonstrated in the more than 400 peer-reviewed publications from OMRC faculty. Most of the proposed Core Laboratories were developed under NIDCD P01 support from 1978 to 1996. The Analytical Pathobiology Core will continue to provide expertise and techniques in microbiology, immunology, biochemistry, molecular biology, and histopathology. It will also provide antibodies, probes, archival samples, bacteria or bacterial components, and a complete range of histological and molecular biological services on human and animal temporal bones. Services include light and electron microscopy, histochemistry, immunohistochemistry, immunogold, quantitative image analysis, Northern blot, RNA protection assay, Western blot, in situ hybridization, competitive RT-PCR, representative differential display, and molecular expression and cloning. Immunological expertise includes immunoassay development, immunological reagent production, molecular characterization of a pneumococcal library used in otitis media animal modeling, and refinement of animal modeling surgical techniques. The Human Subjects & Biostatistics Core will continue to be responsible for assisting base project PIs in study design, data collection and processing, quality control, data storage and retrieval, and data analysis of all studies to provide all

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investigators with a high level and broad range of expertise in data management and analysis. A unique feature of the Core will be the provision of pilot data for new projects drawing from databases and participants from previous OM studies. The key areas are quality control and standardization of data analyses. The key areas are in both Cores are quality assurance, assay standardization, and utilization of the most sensitive methodologies available. Together, the Cores will greatly enhance the OMRC infrastructure, allowing highly productive basic and clinical scientists to conduct research on a broad range of middle and inner ear disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OTITIS MEDIA: PARENT EDUCATION TO AVOID ANTIBIOTIC USE Principal Investigator & Institution: Mc Cormick, David P.; Pediatrics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONING

OTOREFLECTANCE

ASSESSMENT

OF

MIDDLE-EAR

Principal Investigator & Institution: Keefe, Douglas H.; Professor; Sonicom, Inc. 8105 Cedar St Omaha, Ne 68124 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 25-SEP-2004 Summary: (provided by applicant): Otoreflectance (OR) is a new class of hearing test instruments utilizing acoustic signals presented and recorded in the ear canal. OR instruments address limitations in existing screening and diagnostic instruments in such areas as: (1) detecting otitis media, (2) predicting conductive hearing loss, (3) augmenting the newborn hearing screening protocol to test for middle-ear dysfunction, and (4) the general assessment of middle-ear functioning at frequencies important for speech perception. OR provides calibrated measurements over a frequency range from approximately 0.25 to 8 kHz of such transfer functions as reflectance and admittance, and the power absorbed by the ear canal and middle ear. Energy reflectance and absorbed power are OR functions that are relatively insensitive to the position of the probe in the ear canal. This property may allow clinical interpretation of these functions at moderate and high frequencies at which the tympanometric admittance, which is sensitive to probe position, becomes difficult to interpret. One proposed class of OR instruments can be used with probes similar to otoacoustic emission probes to screen middle-ear functioning in several seconds at ambient pressure in the ear canal. Such rapidly performed measurements at ambient pressure may provide a test of middle-ear dysfunction in newborn hearing screening programs, and a test to screen for conductive hearing loss in children at risk for otitis media with effusion. Another proposed class of OR instruments, for which a static pressure pump will be added to the probe system, will be used to measured reflectance, admittance and absorbed power as functions of both frequency and static pressure in the ear canal. Such OR tympanometry instruments may have general audiological and screening utility for diagnosing middle-ear pathology due to the fact that the energy reflectance tympanogram has more orderly patterns at moderate and high frequencies than multifrequency tympanometers based only on admittance. A third proposed class of OR instruments may provide a sensitive test of the acoustic reflex threshold by measuring the wideband shift in OR responses

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elicited by a contralateral or ipsilateral activator sound. A protocol to measure suprathreshold reflex decay may provide additional wideband information that is unavailable in clinical reflex testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARENTAL INPUT LANGUAGE DEVELOPMENT AND OTITIS MEDIA Principal Investigator & Institution: Yont, Kristine M.; Human Development/Psychology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2001; Project Start 01-DEC-2000 Summary: The proposed research is part of a longitudinal study that examines outcomes of children with otitis media (OM). The broad goals of the larger study are to use more sophisticated procedures to document children's hearing and middle ear functioning, to measure factors (e.g., ambient noise) that may exacerbate children's inability to hear during periods of OM-related hearing loss, and to document quality of care, both in the home and daycare, and its effects on children's outcomes. The contribution of the proposed research focuses on a fine-grained analysis of children's language abilities and parental interaction styles at 12 and 24 months. This research project provides a unique opportunity to examine microlevel language processes in a subgroup of children (i.e., children with OM) for which little is known about their language development. Participants in this study consist of a randomized sample from a larger cohort of children stratified for the presence of chronic OM. Mother- father-child language samples will be videotaped in children's homes at 12 and 24 months and analyzed for children';s syntactic, semantic, and pragmatic abilities and for parental interaction styles. Early communicative intents and conversational breakdowns will be examined in children with chronic OM and children without chronic OM using analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA), respectively. Mothers' input styles (e.g., clarification requests and amount of joint focused attention) with children who have chronic OM and children without chronic OM will be examined using an ANOVA. A similar analysis will be used for fathers' input styles. Multiple regression analysis will be used to investigate the main effects of OM, parental input, and the OM x parental input interaction on children's language development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF MUCOSAL INFLAMMATION Principal Investigator & Institution: Hebda, Patricia A.; Associate Professor; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001 Summary: The hydrops ex vacuo mechanism relating Eustachian (ET) dysfunction to otitis media with effusion (OME) descried by Politzer has been more completely developed by investigators at our Center. This mechanism includes four casually related, temporally sequential events: 1) the unabated absorption of middle ear (ME) gases (ET dysfunction); 2) a resultant ME under-pressure; 3) an increased permeability of the mucosal vasculature, and 4) a transduction of fluid into the ME space. The mechanism is supported by studies of the behavior of other biological gas pockets and is consistent with the predictions of mathematical mod4ls of ME pressure regulation. Recent studies conducted by us showed that hydrops ex vacuo is a valid explanation for the development and persistence of OME under appropriate conditions. However, the

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mechanism responsible for transducing the biological signal(s) associated with the under-pressure and initiating ME mucosal inflammation is not known, and has not been studied. While osmotic and hydrostatic effects have been implicated as co-factors, biochemical assays document the presence within the provoked effusion of both proinflammatory cytokines and other chemicals that may have a transducing function as was demonstrated for OME of other etiologies. Because transduction of this signal initiates the inflammatory process, it represents a potential target for other etiologies. Because transduction of this signal initiates the inflammatory process, it represents a potential target for therapies designed to present mucosal inflammation and OME. Therefore, the primary goal of this project is to define the mechanism for signal transduction including: the nature of the signal (e.g. under-pressure, altered gas composition), the sensory components for signal identification (e.g. osmotic, chemoreceptive, baroreceptive), the early cellular response to the signal (e.g. synthesis of cytokines gap juncture disruption), the role of inflammatory chemicals as secondary signals (e.g. lipid based inflammatory mediators, cytokines) and the physiological response of the mucosa to the primary and secondary signals (e.g. gap juncture formation, altered transmucosal potentials, fluid transduction, inflammatory cell influx). The experiments will involve in vitro (cell culture) and in vivo model systems, and will include histopathological, biochemical (proteins, mRNA, lipids) and physiological outcomes. As in past studies, pharmacological probes will be used to identify the role of specific inflammatory mediators in this process. The biochemical changes that promote healing of the mucosa or cause the purported ME complications of tympanostomy tubes are not yet known, and will be investigated using the above techniques and methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF THE OTITIS MEDIA CONTINUUM Principal Investigator & Institution: Kim, Youngki; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: Mucoid otitis media is characterized by thick and visco-elastic effusions in the middle ear that reflect high concentrations of mucins. It is one of the most common otologic diseases in children and can ultimately scar the middle ear and lead to persistent hearing loss and communication problems. There is increasing evidence that mucoid otitis media results from the acute forms of otitis media along a continuum. The pathogenesis of this continuum is not well understood, but most likely involves the alteration of mucin metabolism. We proposed to investigate the pathogenic mechanisms of mucoid otitis media focusing on the alteration of mucus cell metaplasia and mucin gene expression as the key events leading to this transition. We will identify factors that modulate gene expression and mucus cell proliferation using primary culture or rat middle ear epithelial cells and experimental models of otitis media. Identifying the triggers that create the transition of acute to chronic otitis media may enable us to develop a noel therapeutic strategy to interrupt these triggers and stop the pathogenesis of this continuum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC EBM-GETTING EVIDENCE USED AT THE POINT OF CARE Principal Investigator & Institution: Davis, Robert L.; Associate Professor; Pediatrics; University of Washington Seattle, Wa 98195

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Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: The applicant plans to study the provision of evidence at the point of pediatric care, in order to increase the application of evidence- based medicine, change physician behavior, and expedite the translation of research into clinical practice. There will be two main questions. First, that use of an evidence-based decision support system at the point of care will improve antibiotic use in specific index pediatric outpatient diseases, and will (i) reduce frequency and duration of antibiotic therapy for otitis media, (ii) reduce duration of therapy for acute sinusitis, (iii) reduce use of bronchodialators in outpatient treatment of bronchiolitis, and (iv) increase use of intranasal steroids for allergic rhinitis. Second, that individualized physician feedback will provide additional benefit, when used in conjunction with the support system. This study will be carried out through a series of randomized controlled trials, implemented at three sites, including academic pediatric and family medicine health care centers, rural and suburban pediatric clinics, and a regional pediatric emergency department. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSIOLOGICAL AND BALANCE DYNAMICS OF CHILDREN'S LINGUSTIC PROCESSING Principal Investigator & Institution: Schwartz, r; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001 Summary: The general aim of this project is to investigate the role of phonological information in the organization and processing of words. This project will extend the behavioral and electrophysiological investigations of processing of auditory and phonetic input, conducted in the preceding projects, to the lexical levels. Children with specific language impairment (SLI) or with a history of chronic otitis media with effusion (OME) with a mild, fluctuating hearing loss share the common characteristic of having limitations or variations in auditory-phonetic input that are assumed to have an impact on the acquisition, representation, and processing of language. In this project, we will focus on the relation of the acoustic-phonetic form of a word to lexical representation, access and processing. The proposed project includes four sets of experiments, each employing a particular experimental paradigm. Experiment Set 1 examines the extent to which phonological features influence the ability to access the lexicon so as to differentiate words from non-words and open versus closed class words that differ along particular segmental dimensions, using a lexical decision task. Experiment Set 2 examines the speed of processing and the duration of retention of specific phonetic cues embedded in words, employing a match/mismatch to sample task. Experiment Set 3 examines the effects of lexical representation on category boundaries in a categorical perception task. Experiment Set 4 examines the effects of lexical representation on category boundaries to examine the extent to which phonological features of words (onset, rhyme) can affect the rapidity of lexical assess of a related word, using a primed lexical decision task. Twenty children (6;0-9-0) in each of the following groups will participate in the behavioral experiments: (1) SLI, (2) OMEplus, and (3) OMEplus (with normal language). Subjects for the electrophysiological experiments will be selected from these groups on the basis of their behavioral performance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PNEUMOCOCCAL BIOFILMS IN OTITIS MEDIA Principal Investigator & Institution: Post, J Christopher.; Director; Allegheny-Singer Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): Otitis media (OM) is the most common reason that an ill child sees a health care provider, receives an antimicrobial or undergoes a general anesthetic. The overprescribing of antibiotics to treat OM is one of the major causes of antibiotic-resistant bacteria. Previous work from the Center for Genomic Sciences (CGS) has shown that culturally-negative middle-ear effusions actually contain bacterial DNA, mRNA and protein. These findings led to the rejection of the previous dogma, which held that chronic OM was a non-bacterial, inflammatory process, with the paradigm that OM is a mucosal biofilm disease. In conjunction with the Center for Biofilm Engineering, CGS has demonstrated that Hemophilus influenza can form biofilms in an animal model and in pediatric otorrhea. Biofilms are complex organizaton of bacteria covered with a protective exopolysaccharide matrix. In this state, bacteria are slow-growing and very resistant to antibiotics. In this application, we extend our work in biofilms by investigating Streptococcus pneumoniae, one of the most common bacteria associated with OM, and the most common respiratory pathogen. Our hypothesis is that understanding the differences in biofilm and planktonic gene expression will identify proteins that can serve either as immunogens for vaccine development, or targets for novel antimicrobial agents. Using state-of- the-art microarray technologies and a robust animal model of OM, the chinchilla, we propose to identify those genes that are necessary for S. pneumoniae to form a biofilm. Combining advances in imaging and molecular biology, we will directly examine the role of the differentially-regulated genes identified by the array technology. Delineating the molecular basis of biofilms will not only advance our understanding of OM, but of chronic infectious disease in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUORUM SENSING IN H. INFLUENZAE OTITIS Principal Investigator & Institution: Smith, Arnold L.; Professor and Chair; Seattle Biomedical Research Institute 4 Nickerson St, Ste 200 Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Otitis media with effusion (OME) is a significant health problem of children. Haemophilus influenzae is one of the major causes of this disease. Features of H. influenzae OME include frequent recurrences and a failure of eradication with antibiotic administration. One hypothesis explaining these features of H. influenzae OME is that the organism is growing as a biofilm in the middle ear. Bacterial biofilms are characteristically insensitive to antibiotic treatment, as well as incapable of elimination by the host inflammatory response. Evidence of a H. influenzae biofilm in children with OME consists of the presence of short-lived, Haemophilusspecific mRNA in the middle ear fluid of these children. Gram-negative bacterial biofilm formation is dependent upon the synthesis of quorum-sensing transcriptional activators, called autoinducers. We have found that H. influenzae; including those isolated from the middle ear possess a gene (HI0491) capable of synthesizing an autoinducer (AI-2). Insertional inactivation of HI0491 in the H. influenzae laboratory strain Rd KW20 results in a mutant, which lacks the ability to form mature biofilm structures, and has decreased susceptibility to antibiotics, a decreased conjugation frequency and decreased survival in an animal model of OME. In this application, we are seeking to characterize biofilm formation by several prototypic "otitic" H. influenzae in vitro, assess experimental OME

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caused by these strains in the weanling rat and chinchillas, determine the role of the autoinducer in this disease and define the role of AI-2 in biofilm development in vitro and in vivo. Understanding the role of AI-2 and biofilm formation in OME will permit strategies to prevent or treat this disease to be devised. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECENT CONFERENCE

ADVANCEES

IN

OTITIS

MEDIA:

RESEARCH

Principal Investigator & Institution: Lim, David J.; Executive Vice President, Research; House Ear Institute 2100 W 3Rd St Los Angeles, Ca 90057 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): Following the common cold, otitis media (OM), or inflammation of the middle ear, is the most frequent illness resulting in visits to physicians and the most common cause of hearing impairment in children. The annual cost associated with OM exceeds $5 billion. The International Symposium on Recent Advances in Otitis Media and the Post-Symposium Research Conference are held every four years. The Eighth Post-Symposium Research Conference on Recent Advances in Otitis Media is scheduled to be held in June 7-8, 2003. The purpose of the Research Conference is to summarize and critically analyze important research findings by world leaders in the field who are assembled for the Symposium. The aims of this PostSymposium and Research Conference are: 1) to review new discoveries that have been made in basic and clinical otitis media research since the seventh "Symposium and Research Conference on Otitis Media," held in 1999; 2) to critically review recent discoveries in epidemiology, genetics, microbiology, immunology, vaccinology, cell and molecular biology, pathogenesis, prevention, diagnosis management and sequelae of otitis media; 3) to identify new research opportunities and to delineate future research directions and priorities; 4) to improve and encourage communication and collaboration between researchers in various disciplines; and 5) to widely disseminate information by publication in a scientific journal. To expedite and ensure the timely completion of the panel report, we are proposing a web-based system, accessible to panel members, where the report material can be deposited for review by the other members of the panel. This process will allow panel chairs to monitor the progress being made and will hasten the completion of the final panel report. In order to ensure worldwide dissemination of the information, the Research Conference Report will be published as a supplement to a professional journal, such as the Annals of Otology, Rhinology and Laryngology, as it has been in the past. Additionally, we plan to post the panel reports on HEI's otitis media web page (with permission from the publisher). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECURRENT OTITIS MEDIA AND COPD: IMMUNITY AND VACCINES Principal Investigator & Institution: Murphy, Timothy F.; Professor; Medicine; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2005 Summary: Otitis media leads to enormous morbidity and to direct annual healthcare costs estimated to be $3 billion in the U.S. Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the U.S. Bacterial infection in COPD causes substantial morbidity and mortality. Two of the three most common bacterial pathogens to cause otitis media and respiratory tract infections in COPD are

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non-typeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. The development of vaccines to prevent otitis media and respiratory tract infections in adults with COPD would have important impact in reducing mortality, preventing morbidity and reducing healthcare costs in these settings. This program project proposes studies which will elucidate the immune response to specific antigens of NTHI and M. catarrhalis. Our hypothesis is that the pattern of respiratory tract infections due to NTHI and M. catarrhalis in children and adults depends on the immune response to specific surface antigens of the organisms. The aims of the project will be accomplished through the efforts of a multi-disciplinary research team which will collaborate to carry out three interrelated projects. Project 1 will characterized the role of human T cell responses to protein P6, a promising vaccine antigen will be determined through studies with carefully defined samples from humans. Project 3 will focus on antigenic characterization of the lipooligosaccharide (LOS) of M. catarrhalis, the role of NOS as an adhesin and the human immune response to determinants on the LOS molecule. An Administrative/Statistical Core will coordinate the program and provide statistical expertise to each of the projects. Since NTHI and M. catarrhalis are exclusively human pathogens, a strong emphasis is placed on elucidation of the human immune response. The proposed studies will advance the field of vaccine development to prevent otitis media and respiratory tract infections in COPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF INTERLEUKIN-8 IN OTITIS MEDIA Principal Investigator & Institution: Wang, Beinan; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant): Nontypeable Haemophilus influenzae (NTHi) is an important etiological agent of otitis media (OM), one of the most common infectious illnesses of childhood in the United States. The molecular mechanism by which NTHi causes OM is not fully understood. Microbial infection-mediated deleterious inflammation is a hallmark of OM. It has been reported that interleukin 8 (IL-8), one of the important inflammatory mediators, is induced by NTHi and plays a significant role in OM pathogenesis. However, the bacterial factors of NTHi responsible for the inflammatory response and the cellular mechanisms involved remain largely elusive. Our preliminary studies indicate that the soluble cytoplasmic fraction of NTFE (NTHi SCF) strongly induces IL-8 secretion. In addition, multiple intracellular signaling pathways are activated in response to NTHi SCF and may involve NTHi-induced IL-8 up-regulation. The long-term goal of this study is to identify NTHi molecules responsible for deleterious inflammation in OM and to understand the cellular and molecular mechanisms by which NTHi soluble cytoplasmic molecules induce the production of inflammatory mediators. Based on our recent findings, we hypothesize that the soluble cytoplasmic molecules of NTHi induce IL-8 up-regulation through p38 and ERK MAPK pathways. To test this hypothesis, we will: (1) Characterize and purify NTHi molecules responsible for the intense IL-8 upregulation; (2) Determine whether NTHi induces IL-8 up-regulation through activation of the p38 MAPK pathway; (3) Determine the contribution of the ERK MAPK pathway in NTHi-induced IL-8 upregulation. Significance: The establishment of an IL-8 expression assay in the laboratory will enable us to test the hypothesis quantitatively at molecular level. Accomplishment of these goals will provide critical and essential information about the molecular and cellular basis for pathogenesis of OM and rational targets for anti -inflammatory intervention.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF SIALYLATED LPS IN H. INFLUENZAE OTITIS MEDIA Principal Investigator & Institution: Goldstein, Richard N.; Associate Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 25-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Nontypable Haemophilus influenzae (NTHi) is a major cause of acute otitis media (AOM) accounting for 20-30% of all episodes. There is also evidence that NTHi is the most frequent pathogen in children with recurrent episodes of AOM. The extensive heterogeneity of outer membrane proteins has been an impediment to identifying effective vaccine candidates against NTHi. In animal models, membrane protein antigens tend to induce homologous, but not heterologous protection. To date, the PI's research on H. influenzae has exclusively focused on phylogenetic characterization of species natural population structure and its use to survey degree of conservation of potential outer membrane protein targets. Because few essential virulence factors have been identified in the pathogenesis of AOM caused by NTHi, the PI carried out a preliminary pilot study to test the hypothesis that sialic acid, a terminal sugar of NTHi lipopolysaccharicle, might be an essential virulence factor in AOM, analogous to the virulence role of sialic acid of LPS in gonococcal and meningococcal infections. These studies capitalized upon the availability of: (i) isogenic pairs of wild-type and LPS sialylation deficient mutants; (ii) the chinchilla animal model for experimental otitis media and (iii) the fine structural analysis of LPS, including data on organisms obtained ex-vivo from the animal model. This pilot study revealed attenuation of infection by the sialic acid deficient mutant strains compared to infection with wild-type organisms. This is consistent with prior studies showing that sialic acid deficient mutants of NTHi are relatively susceptible to complement mediated bactericidal killing by pooled human sera. The current R21 proposal aims to expand this preliminary evaluation of the role of sialic acid in the pathogenesis of AOM. It amalgamates population biology, a validated animal model of AOM, microbial genetics, and structural analysis to determine the role of sialic acid as virulence factor. These data will pave the way for further studies that could be supported by a future R01 application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STREPTOCOCCUS PNEUMONIAE ADHERENCE AND OTITIS MEDIA PATH Principal Investigator & Institution: Demaria, Thomas F.; Otolaryngology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract) Otitis media (middle ear inflammation) ranks first among the most common diagnoses requiring a physician's office visit and recent estimates indicate that virtually all children (99%) will experience a least one episode of otitis media (OM) by age 2. The disease progresses in many children to recurrent infections and chronic inflammation, often with complications and sequalae that include persistent hearing loss nd communication disorders. Streptococcus pneumoniae (Spn), is one of the foremost human pathogens and is the primary nasopharynx, the initial event in the induction of OM and the mechanisms which effect the transition for a colonized state to invasion of the middle ear and the induction of the disease state by Spn are not known. The long term objectives of this proposal are to

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delineate the pathogenic mechanisms involved in Spn adherence, colonization, and invasion of the middle ear and to develop a scientific rationale for the design of novel diagnostic and prevention strategies. The specific aims of this proposal are: 1) To continue to define the role of Spn neuraminidase in the pathogenesis of OM and to assess whether it is a protective antigen and a potential protein-based vaccine candidate, and whether neuraminidase inhibitors are effective in the prevention of Spn nasopharyngeal colonization of OM. 2) To assess the efficacy of lacto-N-neotetraose, a Spn carbohydrate receptor analog, as an anti-infective for nasopharyngeal colonization. 3) To continue to define the mechanisms whereby influenza A virus affects Spn adherence, colonization, and OM. These aims are designed to delineate the initial interaction, adherence, and colonization which represents the first in a series of steps that culminates in otitis media. These studies may suggest avenues for blocking interaction of Spn with host cells either by immunization or direct intervention blockade with isolated receptor moieties or bacterial adhesin components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE/FUNCTION OF BACTERIAL ADHESION PILI Principal Investigator & Institution: Bullitt, Esther S.; Assistant Professor; Biophysics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-APR-2003 Summary: The aim of this research is to understand the structure and assembly of adhesion pili found on pathogenic bacteria, thereby providing insight into how the architecture of these pili supports their role as a virulence factor. Bacterial survival and colonization require attachment of the bacteria to hosts. In many stains, this process is initiated and maintained by pili; in Escherichia coli that cause pyelonephritis, adhesion and virulence depend on P-pili. Hib-pili expressed on the surface of Haemophilus influenzae mediate H. flu's colonization of the upper respiratory tract, and thus its ability to cause diseases such as childhood meningitis, otitis media, and pneumonia of the elderly. As bacteria become more resistant to traditional antibiotics, it is important to develop new therapies against bacterial infections. Structural information about adhesion pili will provide a basis for future rational design of new therapies to prevent bacterial binding or to remove pathogenic bacteria bound to the human host. The proposed research addresses this long-term goal through structural studies of bacterial adhesion pili. These studies focus on: 1) electron microscopy and three-dimensional (3D) helical reconstruction of P-pili preserved in vitreous ice and of Hib-pili negative stain, 2) controlled damage/recovery of pili to investigate the possibility of re-formation of intact helical filaments, 3) investigation of the 3-D structure of P-pili with mutant structural proteins (pilins), to examine regions of the PapA pilin essential for their assembly into tightly coiled helical filaments, 4) bacterial attachment assays, to assess the effect of mutations and the effect of damage on bacterial binding, and 5) in vitro reconstitution of hetero-pilin polymers from chaperone-pilin complexes, to improve our understanding of the bioassembly process of a prototypical macromolecule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE-FUNCTION DEHYDROGENASE 2

OF

ENTAMOEBA

ALCOHOL

Principal Investigator & Institution: Stanley, Samuel L.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006

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Summary: Nontypeable Haemophilus influenzae (NTHi) causes infections in chronic obstructive pulmonary disease (COPD) and otitis media (OM). Both are characterized by inflammation. The molecular mechanisms underlying NTHi-induced inflammation remain poorly defined. Our long-term objective is to understand the molecular mechanisms by which the inflammatory response is induced and regulated in NTHi infections. Our recent studies showed that NTHi strongly activates nuclear factorkappaB (NF- kappaB) via Toll-like Receptor 2 (TLR2), a newly identified receptor for bacteria. Because TLR2 expression in airway epithelial cells is low and overexpression of TLR2 greatly enhances NTHi-induced NF-kappaB activation, we hypothesize that NTHi up-regulates TLR2 via a specific signaling network. Our preliminary results indeed indicate that NTHi strongly up- regulates TLR2 via a positive NF-kappaB pathway and a negative p38 MAPK pathway. Moreover, glucocorticoids synergistically- enhance NTHi-induced TLR2 up-regulation. These encouraging results have thus laid a solid foundation for further investigation of the molecular mechanisms underlying NTHiinduced TLR2 up-regulation (short-term objective). Aim 1. Determine the contribution of NF-kappaB activation to NTHi-induced TLR2 up- regulation by perturbing NFkappaB signaling pathways. Aim 2. Determine the contribution of p38 MAPK signaling pathway to NTHi- induced TLR2 up-regulation by perturbing p38 signaling pathway. Aim 3. Determine the signaling mechanisms by which glucocorticoids synergistically enhance NTHi-induced TLR2 up- regulation by studying the effect of glucocorticoids on NTHi- induced activation of p38 pathway. Significance: Understanding the signaling mechanisms underlying NTHi-induced TLR2 up- regulation will not only bring new insights into the regulation of inflammation, but will also open up novel therapeutic targets for modulating inflammatory responses in COPD and OM. Moreover, elucidating the molecular mechanisms by which glucocorticoids enhance NTHi-induced TLR2 up-regulation will provide instructive information regarding how to use glucocorticoids more appropriately in the clinic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDY OF S PNEUMONIAE VIRULENCE GENE REGULATION Principal Investigator & Institution: Camilli, Andrew; Associate Professor; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-SEP-2004 Summary: (provided by applicant): The overall goal of our research is to understand the pathogenicity of Streptococcus pneumoniae, the most common cause of bacteremia, bacterial meningitis, otitis media and community-acquired pneumonia in the U.S.A. Current capsule-based vaccines, which only contain a subset of the capsular types in circulation, do not provide adequate protection from pneumonia and otitis media, which account for the majority of S. pneumoniae morbidity. Despite more than a century of research, understanding of S. pneumoniae virulence factors is limited. Furthermore, almost nothing is known concerning the regulation of S. pneumoniae virulence factors during infection. These limitations, plus an increasing incidence of antibiotic-resistance mandate increased study of the pathogenicity of this organism. We have completed a large-scale screen that resulted in the identification of 233 genes that are essential in a murine model of pneumonia. Additionally, we tested the importance of each of these genes in murine models of bacteremia and nasopharygeal carriage. Included among these novel virulence factors are 21 surface proteins, and 20 putative regulators that we hypothesize coordinate tissue-specific virulence gene expression. The first goal of the proposed work is to gain an understanding of both the regulation and mechanisms of action of two factors hypothesized to localize to the bacterial surface and

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interact with host components. Mutational analyses and virulence assays will be combined to define their interacting domains. The second goal is to identify major virulence gene regulons and their modes of coordination during infection. Five putative transcription factors identified in our screen will be placed under inducible expression, and the subset of genes regulated by each will be determined by transcriptional profiling on microarrays. For selected genes, the level of expression during nasopharyngeal carriage in mice and humans will be determined using quantitative RTPCR. The requirement for each cognate regulator for expression of these virulence genes during infection of mice will be confirmed. These studies will enhance our knowledge and understanding of S. pneumoniae-host interactions and virulence mechanisms, and will constitute the first broad study of S. pneumoniae virulence gene regulation. These studies will aid in the development of novel vaccines, and will suggest new targets for antimicrobial drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURFACE PROTEINS OF MORAXELLA CATARRHALIS Principal Investigator & Institution: Hansen, Eric; Professor; Microbiology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAR-2007 Summary: (provided by applicant): Moraxella (Branhamella) catarrhalis is now acknowledged to be an important cause of otitis media in infants and young children and can also cause lower respiratory tract infections in adults with chronic obstructive pulmonary disease. Little is known about the gene products that allow M. catarrhalis to colonize the nasopharynx and then cause disease in the respiratory tract. However, the ability to attach to human cells and to resist killing by normal human serum (i.e., serum resistance) are well-recognized bacterial virulence factors. We have identified two different proteins (UspA1 and UspA2) that are exposed on the surface of this pathogen and that perform distinct functions relevant to the ability of M. catarrhalis to colonize and survive in vivo. We already have established that UspA1 is an adhesin that binds human epithelial cells in vitro. We also have proven that UspA2 is directly involved in the expression of serum resistance by this organism. This research project involves investigation of the structure-function relationships inherent in these two proteins and also addresses two other topics that are relevant to the infectious process involving M. catarrhalis. In the first Specific Aim, we will identify the amino acid sequence(s) in the UspA1 protein that allows it to bind human epithelial cells. In the second Specific Aim, we will identify both the mechanism by which UspA2 confers serum resistance on M. catarrhalis and the amino acid sequence(s) in UspA2 responsible for this activity. Experiments designed to determine the level of UspA2 required for serum resistance and how UspA2 expression is regulated constitute the third Specific Aim. Finally, we will investigate biofilm formation by M. catarrhalis and identify gene products involved in this biologically relevant process in the fourth Specific Aim. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ULTRASONIC DETECTION OF MIDDLE EAR EFFUSION Principal Investigator & Institution: Lewandowski, Jan J.; Director of Res. & Development; Biomec, Inc. 1771 E 30Th St Cleveland, Oh 44114 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 14-MAR-2002 Summary: (Verbatim from the Abstract): Existing non-invasive diagnostic methods for otitis media, such as tympanometry, have inadequate specificity and sensitivity.

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Complications of undiagnosed OM can include hearing loss. In combination, unsatisfactory diagnostic techniques and the gravity of the complications and often lead to unnecessary over-medication of children. This may in turn lead to the development of antibiotic resistance. We will develop a non-invasive ultrasonic device that will detect the presence of middle ear effusion with high accuracy, and it will distinguish the serous or mucoid character of the fluid. The proposed detector will utilize novel miniature broadband piezoelectric transducers developed at Case Western Reserve University. The detection of effusion will be accomplished by analysis of the echo reflected from the distal plane of the tvrnpanic membrane. The rheological properties of the fluid will be determined by attenuation analysis of the echo reflected from the wall of the inner ear. An in vitro study will be done on a physical model of the human ear. After successful in vitro evaluation of the detector, a limited clinical study will be conducted on patients scheduled for tube placement. The performance of the detector will be compared to the results obtained with myringotomy. PROPOSED COMMERCIAL APPLICATION: A new diagnostic device for otitis media will be developed. Otitis media prompts more than 24.5-30 million physician visits per year. The United States market size for treatment of otitis media is between $3-4 billion dollars annually. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UP REGULATION OF MUCIN GENE TRANSCRIPTION--OTITIS MEDIA Principal Investigator & Institution: Li, Jian-Dong; Scientist Ii Section Chief; House Ear Institute 2100 W 3Rd St Los Angeles, Ca 90057 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: Otitis media (OM) is the most common childhood infection and also the leading cause of conductive hearing loss in children. While it has been shown that overproduction of mucin, the major protein of mucus in the middle ear, plays an important role in the development of conductive hearing loss, little is known about the molecular mechanisms underlying mucin overproduction. Our long- term goal is to understand the molecular mechanisms by which mucin is up-regulated in OM. Based on our recent studies showing up-regulation of mucin transcription by Gram negative bacterium Pseudomonas aeruginosa in cystic fibrosis and that nontypeable Haemophilus infuenzae (NTHi) is known to be a major Gram negative bacterial pathogen in OM, we hypothesize that NTHi surface molecules up-regulate mucin gene transcription via activation of specific signaling pathways in middle ear epithelial cells. Recent advances in cloning promoter of mucin MUC5AC gene and establishing middle ear epithelial cell lines offer the opportunity to address the proposed hypothesis at molecular and cellular levels. Our preliminary results indicate that NTHi outer membrane proteins (OMPs) up-regulate mucin MUC5AC transcription via activation of a p38 MAP kinase signaling pathway. These encouraging results have thus laid a solid foundation for further investigation of the molecular mechanisms underlying NTHiinduced mucin transcription. Aim 1. Identify bacterial surface molecules responsible for mucin induction by purifying NTHi surface OMPs using chromatography and testing the fractions and proteins for mucin-inducing ability using luciferase assay. Aim 2. Determine the major intracellular signaling pathway required for NTHi-induced mucin transcription by using specific inhibitors and overexpressing dominant-negative mutants. Aim 3. Identify the NTHi response elements in the mucin MUC5AC gene promoter region and the cognate transcription factors by mutagenesis of MUC5AC promoter, using luciferase assay and gel mobility shift assay. Significance: These studies

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will provide new insights into the molecular pathogenesis of OM and open up new therapeutic targets for inhibition of mucus overproduction to prevent conductive hearing loss and recurrent infection in OM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VACCINE TRIALS USING INDIVIDUAL AND ECOLOGICAL UNITS Principal Investigator & Institution: Koopman, James; Professor; None; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 30-MAR-2003 Summary: Vaccines prevent illness both by decreasing individual risk of acquiring illness and preventing transmission. Clinical trials for testing vaccines have classically focused on disease prevention. with random assignment to individuals. However, other outcome measures and randomization to family or other units may be desirable. We will develop and apply a general methodology for assessing the consequences of vaccine trial design decisions using computer simulations that model a broad range of factors known to influence infection transmission and control. The specific vaccine to be examined is one that is under development for non-typeable Haemophilus influenzae (NTHi). a common cause of otitis media and sinusitis. Specifically, we propose to: (1) determine the power to detect useful effects of trial designs that randomize vaccine and placebo to individuals, family units, or daycare centers; (2) determine how well the effect parameters estimated from these different designs predict the ability of vaccination programs to control infection; (3) determine the sensitivity of power and predictive accuracy of vaccine trial designs to: (a) details in the trial design such as whether clinical otitis or nasopharyngeal culture is used as an outcome; (b) transmission dynamics in the study population; (c) biological aspects of NTHi infection; (d) biological effects of the vaccines; (4) determine whether standard statistical methods erroneously assess the significance and power of vaccine effect measurements. The sensitivity analysis will be performed using recent advances in the area of response surface analysis and experimental design. The models to be simulated represent a significant advance in combining analytical tractability with flexibility to include geographic and social space determinants of contact patterns, biologically defined vaccine effects, and detailed natural histories of infection. The analysis performed will provide the vaccine trial designer with comparisons of power and predictive accuracy that reveal the relative trial sizes, data completeness. and data accuracy that are needed to attain comparable utility from different trial designs. They will also provide insight regarding how different biological effects of vaccines generate different population effects of vaccine programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WATER PRECAUTIONS AND TYMPANOSTOMY TUBES Principal Investigator & Institution: Mandel, Ellen M.; Children's Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213

Hosp

Timing: Fiscal Year 2001 Summary: Children with tympanostomy tubes have traditionally been advised to protect their ears when swimming and bathing. Although acute otorrhea through a patent tube is a common occurrence, there is no published evidence that water exposure is causative. We will prospectively randomize 182 children, ages 6 months to 6 years, who have had bilateral tympanostomy tubes placed within one month of entry to one of 2 groups: 1) swimming and bathing without earplugh or 2) swimming and bathing with

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earplugs. We will stratify the groups by age (4 years) and by diagnosis (recurrent acute otitis media, otitis media with effusion). Parents will be given a calendar to record all swimming acitvity. The children will be seen monthly for one year, and whenever there is an intercurrent ear, nose, or throat problem. If otorrhea develops, a culture will be performed and the child will be treated with an oral antibiotic and ototopical drops. The primary comparison will be the incidence of otorrhea in each experimental group and the second comparison will be the average number of episodes per child in the two group. Examination of the culture results will help determine the pathogenic mechanisms responsible for the otorrhea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: XYLITOL FOR ACUTE OTITIS MEDIA PROPHYLAXIS Principal Investigator & Institution: Vernacchio, Louis; Epidemiology and Biostatistics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Acute otitis media (AOM) is one of the most common illnesses of childhood, with a peak incidence between 6 and 24 months of age. AOM is also the most common indication for antibiotic use among U.S. children, and as such, contributes significantly to the growing problem of antimicrobial resistance. A safe and effective means of preventing AOM without the use of antibiotics would be of great public health importance. Xylitol, a naturally occurring sugar alcohol, has been proposed as a prophylactic therapy for AOM. In two recent, well-designed, randomized, double-blind clinical trials conducted by a single research team in Finland, daily treatment with xylitol for two to three months was found to reduce the cumulative incidence of AOM in children by 30-40%, and to reduce antibiotic use by 36%. Older children consumed xylitol in the form of a chewing gum or lozenge, while children too young to chew gum received xylitol as syrup. However, most participants in the Finnish trials were beyond the age range of greatest risk for AOM, and all received xylitol five times per day. If xylitol is to be useful as a widespread prophylactic treatment for AOM, it must be shown that it can be given safely over several months to children between 6 and 24 months of age and that it is effective when given less frequently than five times per day. The applicants' ultimate goal is to conduct a large randomized controlled trial (RCT) to test whether xylitol, given one to three times a day as an aqueous solution to children between the ages of 6 and 24 months, significantly reduces the risk of AOM and antibiotic use. The current application proposes a two-phase pilot study to collect preliminary data necessary to ensure the success of a large RCT. Phase I consists of a seven-day dose-ranging tolerability study intended to determined the palatability and side effects (particularly gastrointestinal symptoms) of varying doses of xylitol solution given to children six to 24 months of age. Phase II consists of a six-month pilot RCT of xylitol solution versus control (sorbitol) solution administered once daily or three times a day to children six to 24 months old for six months. The pilot RCT will be conducted within the SIone Epidemiology Unit Network of Pediatricians and Family Practitioners, a nationwide physician research network. The pilot RCT will allow testing and refinement of subject enrollment procedures and data collection instruments. A preliminary estimate of the effect size of xylitol treatment from the pilot RCT will suggest whether the effect if sufficiently large to warrant a large formal RCT to be proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

A New Rat Model of Otitis Media Caused by Streptococcus pneumoniae: Conditions and Application in Immunization Protocols. by van der Ven LT, van den Dobbelsteen GP, Nagarajah B, van Dijken H, Dortant PM, Vos JG, Roholl PJ.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96998

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Adenovirus serotype 1 does not act synergistically with Moraxella (Branhamella) catarrhalis to induce otitis media in the chinchilla. by Bakaletz LO, Murwin DM, Billy JM.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173592

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Adhesin Expression in Matched Nasopharyngeal and Middle Ear Isolates of Nontypeable Haemophilus influenzae from Children with Acute Otitis Media. by Krasan GP, Cutter D, Block SL, St. Geme JW III.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96336

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Amoxicillin treatment of experimental acute otitis media caused by Haemophilus influenzae with non-beta-lactamase-mediated resistance to beta-lactams: aspects of virulence and treatment. by Melhus A, Janson H, Westman E, Hermansson A, Forsgren A, Prellner K.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164048

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An evidence based approach to reducing antibiotic use in children with acute otitis media: controlled before and after study. by Cates C.; 1999 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27785

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Bacterial Cytolysin Perturbs Round Window Membrane Permeability Barrier In Vivo: Possible Cause of Sensorineural Hearing Loss in Acute Otitis Media. by Engel F, Blatz R, Schliebs R, Palmer M, Bhakdi S.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107896

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Bactericidal/Permeability-Increasing Protein Prevents Mucosal Damage in an Experimental Rat Model of Chronic Otitis Media with Effusion. by Nell MJ, Koerten HK, Grote JJ.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97515

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

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

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Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children. by Dagan R, Leibovitz E, Fliss DM, Leiberman A, Jacobs MR, Craig W, Yagupsky P.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89626

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Blinded Multiplex PCR Analyses of Middle Ear and Nasopharyngeal Fluids from Chinchilla Models of Single- and Mixed-Pathogen-Induced Otitis Media. by Bakaletz LO, White GJ, Post JC, Ehrlich GD.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121361

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Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media. by Engel F, Blatz R, Kellner J, Palmer M, Weller U, Bhadki S.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173151

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Characterization of ear fluid isolates of Alloiococcus otitidis from patients with recurrent otitis media. by Bosley GS, Whitney AM, Pruckler JM, Moss CW, Daneshvar M, Sih T, Talkington DF.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228599

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Comparative evaluation of loracarbef and amoxicillin-clavulanate for acute otitis media. by Gan VN, Kusmiesz H, Shelton S, Nelson JD.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245137

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Comparative study of once-weekly azithromycin and once-daily amoxicillin treatments in prevention of recurrent acute otitis media in children. by Marchisio P, Principi N, Sala E, Lanzoni L, Sorella S, Massimini A.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163612

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Comparison of Alteration of Cell Surface Carbohydrates of the Chinchilla Tubotympanum and Colonial Opacity Phenotype of Streptococcus pneumoniae during Experimental Pneumococcal Otitis Media with or without an Antecedent Influenza A Virus Infection. by Tong HH, Grants I, Liu X, DeMaria TF.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128169

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Detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins confers protection against otitis media in chinchillas. by Gu XX, Sun J, Jin S, Barenkamp SJ, Lim DJ, Robbins JB, Battey J.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175645

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Effect of Influenza A Virus Infection on Nasopharyngeal Colonization and Otitis Media Induced by Transparent or Opaque Phenotype Variants of Streptococcus pneumoniae in the Chinchilla Model. by Tong HH, Weiser JN, James MA, DeMaria TF.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97928

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Effect of recolonisation with "interfering" [alpha] streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. by Roos K, Hakansson EG, Holm S.; 2001 Jan 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26587

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Efficacy of clarithromycin treatment of acute otitis media caused by infection with penicillin-susceptible, -intermediate, and -resistant Streptococcus pneumoniae in the chinchilla. by Alper CM, Doyle WJ, Seroky JT, Bluestone CD.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163435

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Efficacy of Linezolid in Experimental Otitis Media. by Pelton SI, Figueira M, Albut R, Stalker D.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89742

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Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillinand cephalosporin-resistant Streptococcus pneumoniae. by Barry B, Muffat-Joly M, Bauchet J, Faurisson F, Gehanno P, Pocidalo JJ, Carbon C.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163458

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Eradication by Ceftriaxone of Streptococcus pneumoniae Isolates with Increased Resistance to Penicillin in Cases of Acute Otitis Media. by Gehanno P, Nguyen L, Barry B, Derriennic M, Pichon F, Goehrs JM, Berche P.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89013

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Establishing Criteria for Assessment of Efficacy of Antimicrobial Agents in Acute Otitis Media. by Erhardt W, Murphy M, Knirsch C.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90118

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Evaluation of Phase Variation of Nontypeable Haemophilus influenzae Lipooligosaccharide during Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model. by Tong HH, Blue LE, James MA, Chen YP, DeMaria TF.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98384

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Evaluation of the Virulence of a Streptococcus pneumoniae Neuraminidase-Deficient Mutant in Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model. by Tong HH, Blue LE, James MA, DeMaria TF.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97223

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Evaluation of the virulence of nontypeable Haemophilus influenzae lipooligosaccharide htrB and rfaD mutants in the chinchilla model of otitis media. by DeMaria TF, Apicella MA, Nichols WA, Leake ER.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175637

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Experimental Acute Otitis Media Due to Nontypeable Haemophilus influenzae: Comparison of High and Low Azithromycin Doses with Placebo. by Babl FE, Pelton SI, Li Z.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127299

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Expression of Cytokine Genes during Pneumococcal and Nontypeable Haemophilus influenzae Acute Otitis Media in the Rat. by Melhus A, Ryan AF.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101687

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Household Transmission of Streptococcus pneumoniae among Siblings with Acute Otitis Media. by Shimada J, Yamanaka N, Hotomi M, Suzumoto M, Sakai A, Ubukata K, Mitsuda T, Yokota S, Faden H.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130916

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Identification of Common Lipooligosaccharide Types in Isolates from Patients with Otitis Media by Monoclonal Antibodies against Nontypeable Haemophilus influenzae 9274. by Ueyama T, Gu XX, Tsai CM, Karpas AB, Lim DJ.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95667

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Identification of the Lipooligosaccharide Biosynthesis Gene lic2B as a Putative Virulence Factor in Strains of Nontypeable Haemophilus influenzae That Cause Otitis Media. by Pettigrew MM, Foxman B, Marrs CF, Gilsdorf JR.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128108

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Immunization with high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae modifies experimental otitis media in chinchillas. by Barenkamp SJ.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173911

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Immunization with outer membrane protein P6 from nontypeable Haemophilus influenzae induces bactericidal antibody and affords protection in the chinchilla model of otitis media. by DeMaria TF, Murwin DM, Leake ER.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174506

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In vivo correlates for Streptococcus pneumoniae penicillin resistance in acute otitis media. by Gehanno P, Lenoir G, Berche P.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162525

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In Vivo Efficacies of Amoxicillin and Cefuroxime against Penicillin-Resistant Streptococcus pneumoniae in a Gerbil Model of Acute Otitis Media. by Cenjor C, Ponte C, Parra A, Nieto E, Garcia-Calvo G, Gimenez MJ, Aguilar L, Soriano F.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105604

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Intranasal Immunization Enhances Clearance of Nontypeable Haemophilus influenzae and Reduces Stimulation of Tumor Necrosis Factor Alpha Production in the Murine Model of Otitis Media. by Sabirov A, Kodama S, Hirano T, Suzuki M, Mogi G.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98249

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Middle Ear Fluid Cytokine and Inflammatory Cell Kinetics in the Chinchilla Otitis Media Model. by Sato K, Liebeler CL, Quartey MK, Le CT, Giebink GS.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96550

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Nasopharyngeal antibodies to pneumococcal pneumolysin in children with acute otitis media. by Virolainen A, Jero J, Kayhty H, Karma P, Eskola J, Leinonen M.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170225

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Nonencapsulated Haemophilus influenzae in Aboriginal infants with otitis media: prolonged carriage of P2 porin variants and evidence for horizontal P2 gene transfer. by Smith-Vaughan HC, Sriprakash KS, Mathews JD, Kemp DJ.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175155

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Nontypeable Haemophilus influenzae Gene Expression Induced In Vivo in a Chinchilla Model of Otitis Media. by Mason KM, Munson Jr. RS, Bakaletz LO.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155704

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Optimal Dose of Amoxicillin in Treatment of Otitis Media Caused by a PenicillinResistant Pneumococcus Strain in the Gerbil Model. by Parra A, Ponte C, Cenjor C, Garcia-Calvo G, Gimenez MJ, Aguilar L, Soriano F.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127470

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Otitis media with effusion in infants: Is screening and treatment with ventilation tubes necessary? by Rovers MM, Ingels K, van der Wilt GJ, Zielhuis GA, van den Broek P.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81541

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Passive Transfer of Antiserum Specific for Immunogens Derived from a Nontypeable Haemophilus influenzae Adhesin and Lipoprotein D Prevents Otitis Media after Heterologous Challenge. by Kennedy BJ, Novotny LA, Jurcisek JA, Lobet Y, Bakaletz LO.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97485

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Pharmacokinetics and Efficacy of Linezolid in a Gerbil Model of Streptococcus pneumoniae-Induced Acute Otitis Media. by Humphrey WR, Shattuck MH, Zielinski RJ, Kuo MS, Biermacher JJ, Smith DP, Jensen JL, Schaadt RD, Zurenko GE, Richards IM.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152499

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Pharmacokinetics of azithromycin in pediatric patients with acute otitis media. by Nahata MC, Koranyi KI, Luke DR, Foulds G.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162845

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Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. by Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J.; 2001 Feb 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26576

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Predictors of poor outcome and benefits from antibiotics in children with acute otitis media: pragmatic randomised trial. by Little P, Gould C, Moore M, Warner G, Dunleavey J, Williamson I.; 2002 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116668

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Prevalence of Antimicrobial-Resistant Pathogens in Middle Ear Fluid: Multinational Study of 917 Children with Acute Otitis Media. by Jacobs MR, Dagan R, Appelbaum PC, Burch DJ.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105503

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Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. by Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA.; 2000 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27282

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Protection against Development of Otitis Media Induced by Nontypeable Haemophilus influenzae by Both Active and Passive Immunization in a Chinchilla Model of Virus-Bacterium Superinfection. by Bakaletz LO, Kennedy BJ, Novotny LA, Duquesne G, Cohen J, Lobet Y.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96578

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Rationale behind high-dose amoxicillin therapy for acute otitis media due to penicillin-nonsusceptible pneumococci: support from in vitro pharmacodynamic studies. by Lister PD, Pong A, Chartrand SA, Sanders CC.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164037

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Reply to "Establishing Criteria for Assessment of Efficacy of Antimicrobial Agents in Acute Otitis Media". by Dagan R, Leibovitz E.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116694

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Role of Macrophage Migration Inhibitory Factor in Otitis Media with Effusion in Adults. by Kariya S, Okano M, Aoji K, Kosaka M, Chikumoto E, Hattori H, Yuen K, Nishioka S, Nishioka K, Nishizaki K.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154972

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Roles of autolysin and pneumolysin in middle ear inflammation caused by a type 3 Streptococcus pneumoniae strain in the chinchilla otitis media model. by Sato K, Quartey MK, Liebeler CL, Le CT, Giebink GS.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173895

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Screening for otitis media with effusion: Recommendation statement from the Canadian Task Force on Preventive Health Care. by Care C.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81561

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Streptococcus pneumoniae Causes Experimental Meningitis following Intranasal and Otitis Media Infections via a Nonhematogenous Route. by Marra A, Brigham D.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98817

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Transcription of genes encoding iron and heme acquisition proteins of Haemophilus influenzae during acute otitis media. by Whitby PW, Sim KE, Morton DJ, Patel JA, Stull TL.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175673

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Two-Step PCR-Based Assay for Identification of Bacterial Etiology of Otitis Media with Effusion in Infected Lebanese Children. by Matar GM, Sidani N, Fayad M, Hadi U.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104796

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Variability of Outer Membrane Protein P1 and Its Evaluation as a Vaccine Candidate against Experimental Otitis Media due to Nontypeable Haemophilus influenzae: an Unambiguous, Multifaceted Approach. by Bolduc GR, Bouchet V, Jiang RZ, Geisselsoder J, Truong-Bolduc QC, Rice PA, Pelton SI, Goldstein R.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98360

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 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

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

A 15-month-old child with recurrent otitis media. Author(s): Paradise JL. Source: Jama : the Journal of the American Medical Association. 2002 November 27; 288(20): 2589-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444866&dopt=Abstract

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A blind parallel comparative study of the efficacy and safety of rovamycin versus augmentin in the treatment of acute otitis media. Author(s): Mgbor NC, Umeh RE. Source: West Afr J Med. 2002 April-June; 21(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403032&dopt=Abstract

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A randomized, placebo-controlled trial of the effect of antihistamine or corticosteroid treatment in acute otitis media. Author(s): Chonmaitree T, Saeed K, Uchida T, Heikkinen T, Baldwin CD, Freeman DH Jr, McCormick DP. Source: The Journal of Pediatrics. 2003 September; 143(3): 377-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517524&dopt=Abstract

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A systematic review of the effectiveness of ofloxaxin otic solution for the treatment of suppurative otitis media. Author(s): Abes G, Espallardo N, Tong M, Subramaniam KN, Hermani B, Lasiminigrum L, Anggraeni R. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 2003 MarchApril; 65(2): 106-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824733&dopt=Abstract

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Acute otitis media and facial nerve paralysis in adults. Author(s): Redaelli de Zinis LO, Gamba P, Balzanelli C. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 January; 24(1): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544039&dopt=Abstract

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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Acute otitis media: bunnies, disposables, and bacterial original sin! Author(s): Block SL. Source: Pediatrics. 2003 January; 111(1): 217-8; Author Reply 217-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509581&dopt=Abstract

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Acute otitis media: more trouble with the evidence. Author(s): Wald ER. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): 103-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586970&dopt=Abstract

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Acute otitis media--a brief explanation to parents and antibiotic use. Author(s): Pshetizky Y, Naimer S, Shvartzman P. Source: Family Practice. 2003 August; 20(4): 417-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876113&dopt=Abstract

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Airway management of a child with temporomandibular joint ankylosis following otitis media 1. Author(s): Das S, Pearce A. Source: Anaesthesia. 2002 December; 57(12): 1227-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437735&dopt=Abstract

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Airway management of a child with temporomandibular joint ankylosis following otitis media 2. Author(s): Cunnington P, Hampson-Evans D. Source: Anaesthesia. 2002 December; 57(12): 1228-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437736&dopt=Abstract

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Amoxicillin/clavulanic acid is ineffective at preventing otitis media in children with presumed viral upper respiratory infection: a randomized, double-blind equivalence, placebo-controlled trial. Author(s): Autret-Leca E, Giraudeau B, Ployet MJ, Jonville-Bera AP. Source: British Journal of Clinical Pharmacology. 2002 December; 54(6): 652-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492614&dopt=Abstract

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Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media. Author(s): Easton J, Noble S, Perry CM. Source: Drugs. 2003; 63(3): 311-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534334&dopt=Abstract

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Antibiotic prescribing for otitis media: how well does it match published guidelines? Author(s): McEwen LN, Farjo R, Foxman B. Source: Pharmacoepidemiology and Drug Safety. 2003 April-May; 12(3): 213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733474&dopt=Abstract

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Antibiotic resistance and choice of antimicrobial agents for acute otitis media. Author(s): Barnett ED. Source: Pediatric Annals. 2002 December; 31(12): 794-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503437&dopt=Abstract

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Antibody response to pneumococcal capsular polysaccharides in children with acute otitis media. Author(s): Soininen A, Lahdenkari M, Kilpi T, Makela PH, Kayhty H. Source: The Pediatric Infectious Disease Journal. 2002 March; 21(3): 186-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005079&dopt=Abstract

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Are antibiotics effective for otitis media with effusion? Author(s): Gasper K, St Anna L. Source: The Journal of Family Practice. 2003 April; 52(4): 321-3; Discussion 322-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681093&dopt=Abstract

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Are nasal steroid sprays effective for otitis media with effusion? Author(s): Chaffee JR, St Anna L. Source: The Journal of Family Practice. 2003 August; 52(8): 647-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899825&dopt=Abstract

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Are tympanostomy tubes indicated for recurrent acute otitis media? Author(s): Wilson SA, Mayo H, Fisher M. Source: The Journal of Family Practice. 2003 May; 52(5): 403-4, 406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737775&dopt=Abstract

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Association between gastroesophageal reflux and sinusitis, otitis media, and laryngeal malignancy: a systematic review of the evidence. Author(s): Weaver EM. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 81S-89S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928081&dopt=Abstract

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Autoimmunity in the etiology of otitis media with effusion. Author(s): Kirglu M, Yildirim I, Aydogan B, Okur E, Tuncer U, Erken E. Source: American Journal of Otolaryngology. 2003 May-June; 24(3): 159-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761702&dopt=Abstract

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Bacterial aetiology of non-resolving otitis media in South African children. Author(s): Huebner RE, Wasas AD, Hockman M, Klugman KP; ENT Study Group. Source: The Journal of Laryngology and Otology. 2003 March; 117(3): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648369&dopt=Abstract

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Bacterial and viral etiology of acute otitis media in Chilean children. Author(s): Rosenblut A, Santolaya ME, Gonzalez P, Corbalan V, Avendano LF, Martinez MA, Hormazabal JC. Source: The Pediatric Infectious Disease Journal. 2001 May; 20(5): 501-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368107&dopt=Abstract

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Bacterial eradication in the treatment of otitis media. Author(s): Dagan R, Leibovitz E. Source: The Lancet Infectious Diseases. 2002 October; 2(10): 593-604. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383609&dopt=Abstract

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Bacterial etiology of otitis media with effusion; focusing on the high positivity of Alloiococcus otitidis. Author(s): Kalcioglu MT, Oncel S, Durmaz R, Otlu B, Miman MC, Ozturan O. Source: New Microbiol. 2002 January; 25(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837388&dopt=Abstract

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Bacterial interference between pathogens in otitis media and alpha-haemolytic Streptococci analysed in an in vitro model. Author(s): Tano K, Hakansson EG, Holm SE, Hellstrom S. Source: Acta Oto-Laryngologica. 2002 January; 122(1): 78-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876603&dopt=Abstract

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Bacterial pathogens of otitis media and sinusitis: detection in the nasopharynx with selective agar media. Author(s): Dudley S, Ashe K, Winther B, Hendley JO. Source: The Journal of Laboratory and Clinical Medicine. 2001 November; 138(5): 338-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709658&dopt=Abstract

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Bacteriocin-like inhibitory substance (BLIS) production by the normal flora of the nasopharynx: potential to protect against otitis media? Author(s): Walls T, Power D, Tagg J. Source: Journal of Medical Microbiology. 2003 September; 52(Pt 9): 829-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909662&dopt=Abstract

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Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children. Author(s): Piglansky L, Leibovitz E, Raiz S, Greenberg D, Press J, Leiberman A, Dagan R. Source: The Pediatric Infectious Disease Journal. 2003 May; 22(5): 405-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792379&dopt=Abstract

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Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media. Author(s): Dagan R, Hoberman A, Johnson C, Leibovitz EL, Arguedas A, Rose FV, Wynne BR, Jacobs MR. Source: The Pediatric Infectious Disease Journal. 2001 September; 20(9): 829-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734759&dopt=Abstract

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Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media. Author(s): Leiberman A, Leibovitz E, Piglansky L, Raiz S, Press J, Yagupsky P, Dagan R. Source: The Pediatric Infectious Disease Journal. 2001 March; 20(3): 260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303827&dopt=Abstract

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Bacteriological and PCR analysis of clinical material aspirated from otitis media with effusions. Author(s): Gok U, Bulut Y, Keles E, Yalcin S, Doymaz MZ. Source: International Journal of Pediatric Otorhinolaryngology. 2001 July 30; 60(1): 4954. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434953&dopt=Abstract

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Bacteriology of acute otitis media in a cohort of Finnish children followed for the first two years of life. Author(s): Kilpi T, Herva E, Kaijalainen T, Syrjanen R, Takala AK. Source: The Pediatric Infectious Disease Journal. 2001 July; 20(7): 654-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465836&dopt=Abstract

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Balance in children with otitis media with effusion. Author(s): Cohen H, Friedman EM, Lai D, Pellicer M, Duncan N, Sulek M. Source: International Journal of Pediatric Otorhinolaryngology. 1997 December 10; 42(2): 107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9692620&dopt=Abstract

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Barotrauma vis-a-vis the “chronic otitis media syndrome”: two conditions with middle ear gas deficiency Is secretory otitis media a contraindication to air travel? Author(s): Sade J, Ar A, Fuchs C. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 March; 112(3): 230-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656414&dopt=Abstract

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Behaviour and developmental effects of otitis media with effusion into the teens. Author(s): Bennett KE, Haggard MP, Silva PA, Stewart IA. Source: Archives of Disease in Childhood. 2001 August; 85(2): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11466180&dopt=Abstract

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beta-Lactamase-producing Moraxella catarrhalis may prevent the emergence of penicillin-resistant Streptococcus pneumoniae in children with recurrent acute otitis media. Author(s): Joki-Erkkila VP, Aittoniemi J, Vuento R, Puhakka H. Source: International Journal of Pediatric Otorhinolaryngology. 2002 May 15; 63(3): 21922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997157&dopt=Abstract

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Bilateral lateral sinus thrombosis associated with otitis media and mastoiditis. Author(s): Samaha M, Prudencio JA, Tewfik TL, Schloss MD. Source: The Journal of Otolaryngology. 2001 August; 30(4): 250-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771039&dopt=Abstract

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Blood group in otitis media with effusion. Author(s): Apostolopoulos K, Labropoulou E, Konstantinos B, Rhageed S, Ferekidis E. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 2002 November-December; 64(6): 433-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499769&dopt=Abstract

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Bordetella pertussis causing otitis media: a case report. Author(s): Decherd ME, Deskin RW, Rowen JL, Brindley MB. Source: The Laryngoscope. 2003 February; 113(2): 226-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567073&dopt=Abstract

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Breakthrough Streptococcus pneumoniae meningitis during clarithromycin therapy for acute otitis media. Author(s): Bochud PY, Calandra T, Moreillon P, Baumgartner JD, Yersin B. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2001 February; 20(2): 1367. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305469&dopt=Abstract

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Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae? Author(s): Leibovitz E, Satran R, Piglansky L, Raiz S, Press J, Leiberman A, Dagan R. Source: The Pediatric Infectious Disease Journal. 2003 June; 22(6): 509-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799507&dopt=Abstract

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Causes for massive bacterial colonization on mucosal membranes during infectious mononucleosis: implications for acute otitis media. Author(s): Stenfors LE, Bye HM, Raisanen S. Source: International Journal of Pediatric Otorhinolaryngology. 2002 September 24; 65(3): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242139&dopt=Abstract

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Cellular proliferation of mucosa-associated lymphoid tissue with otitis media: a preliminary study. Author(s): Haginomori S, Balaban CD, Miura M, Takasaki K, Sando I. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 October; 111(10): 92632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389863&dopt=Abstract

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Changes in management of otitis media: 2003 and beyond. Author(s): Klein JO. Source: Pediatric Annals. 2002 December; 31(12): 824-6, 829. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503440&dopt=Abstract

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Characteristics of the type B tympanogram can predict the magnitude of the air-bone gap in otitis media with effusion. Author(s): Sichel JY, Priner Y, Weiss S, Levi H, Barshtein G, Eliashar R, Elidan J. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 May; 112(5): 450-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784986&dopt=Abstract

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Characterization of cytokines present in pediatric otitis media with effusion: comparison of allergy positive and negative. Author(s): Jang CH, Kim YH. Source: International Journal of Pediatric Otorhinolaryngology. 2002 October 21; 66(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363420&dopt=Abstract

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Childhood otitis media and electrically elicited stapedius reflexes in adult cochlear implantees. Author(s): Todd NW, Ajayi E, Hasenstab MS, Webster DA, Boyd PJ. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 July; 24(4): 621-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851555&dopt=Abstract

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Cholesterol granuloma in the middle fossa presenting 30 years after surgery for chronic otitis media: a case report. Author(s): Muzumdar DP, Goel A, Desai K, Chagla A. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2002 July; 9(4): 447-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217677&dopt=Abstract

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Chronic otitis media with effusion sequelae in children treated with tubes. Author(s): Daly KA, Hunter LL, Lindgren BR, Margolis R, Giebink GS. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 May; 129(5): 517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759263&dopt=Abstract

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Chronic silent otitis media. Author(s): Paparella MM, Schachern PA, Cureoglu S. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 2002 MarchApril; 64(2): 65-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021496&dopt=Abstract

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Chronic suppurative otitis media in indigenous populations: the Australian aborigine. Author(s): Coates H. Source: Ear, Nose, & Throat Journal. 2002 August; 81(8 Suppl 1): 11-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199180&dopt=Abstract

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Chronic suppurative otitis media in school pupils in Nigeria. Author(s): Ologe FE, Nwawolo CC. Source: East Afr Med J. 2003 March; 80(3): 130-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762427&dopt=Abstract

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Chronic suppurative otitis media. Author(s): Clin Evid. 2002 Dec;(8):511-8 Source: Clin Evid. 2002 June; (7): 440-57. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603897

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Chronic suppurative otitis media: a clinical overview. Author(s): Roland PS. Source: Ear, Nose, & Throat Journal. 2002 August; 81(8 Suppl 1): 8-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199189&dopt=Abstract

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Clinical considerations in the diagnosis of otitis media. Author(s): Klaudt MR, Steinbach WJ, Sectish TC. Source: Curr Allergy Asthma Rep. 2003 July; 3(4): 313-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791208&dopt=Abstract

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Clinical practice. Otitis media. Author(s): Hendley JO. Source: The New England Journal of Medicine. 2002 October 10; 347(15): 1169-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374878&dopt=Abstract

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Cochlear implantation in children with otitis media. Author(s): Fayad JN, Tabaee A, Micheletto JN, Parisier SC. Source: The Laryngoscope. 2003 July; 113(7): 1224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838023&dopt=Abstract

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Comparative study between tubotympanic and atticoantral types of chronic suppurative otitis media. Author(s): Chowdhury MA, Alauddin M. Source: Bangladesh Med Res Counc Bull. 2002 April; 28(1): 36-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587759&dopt=Abstract

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Comparison of tone burst and tapping evocation of myogenic potentials in patients with chronic otitis media. Author(s): Yang TL, Young YH. Source: Ear and Hearing. 2003 June; 24(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799539&dopt=Abstract

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Complications of otitis media requiring surgical intervention. Author(s): Long YT, Mahmud R, Sani A, Saim L. Source: Asian J Surg. 2002 April; 25(2): 170-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376240&dopt=Abstract

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Daily home tympanometry to study the pathogenesis of otitis media. Author(s): Antonio SM, Don D, Doyle WJ, Alper CM. Source: The Pediatric Infectious Disease Journal. 2002 September; 21(9): 882-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380590&dopt=Abstract

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Deciding not to measure performance: the case of acute otitis media. Author(s): Mangione-Smith R, Onstad K, Wong L, Roski J. Source: Jt Comm J Qual Saf. 2003 January; 29(1): 27-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528571&dopt=Abstract

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Definition and diagnostic criteria for acute otitis media. Author(s): McCormick DP. Source: Pediatrics. 2002 April; 109(4): 717-8; Author Reply 717-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927723&dopt=Abstract

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Demonstration of RANTES and eosinophilic cataionic protein in otitis media with effusion with allergy. Author(s): Jang CH, Kim YH. Source: International Journal of Pediatric Otorhinolaryngology. 2003 May; 67(5): 531-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697356&dopt=Abstract

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Detection and characterization of pediatric serum antibody to the OMP P5homologous adhesin of nontypeable Haemophilus influenzae during acute otitis media. Author(s): Novotny LA, Pichichero ME, Denoel PA, Neyt C, Vanderschrick S, Dequesne G, Bakaletz LO. Source: Vaccine. 2002 October 4; 20(29-30): 3590-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297406&dopt=Abstract

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Detection of fungal DNA in effusion associated with acute and serous otitis media. Author(s): Kim EJ, Catten MD, Lalwani AK. Source: The Laryngoscope. 2002 November; 112(11): 2037-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439176&dopt=Abstract

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Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Author(s): Pitkaranta A, Virolainen A, Jero J, Arruda E, Hayden FG. Source: Pediatrics. 1998 August; 102(2 Pt 1): 291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9685428&dopt=Abstract

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Development and characterization of a pooled Haemophilus influenzae genomic library for the evaluation of gene expression changes associated with mucosal biofilm formation in otitis media. Author(s): Erdos G, Sayeed S, Antalis P, Hu FZ, Hayes J, Goodwin J, Dopico R, Post JC, Ehrlich GD. Source: International Journal of Pediatric Otorhinolaryngology. 2003 July; 67(7): 749-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791450&dopt=Abstract

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Diagnosis and management of acute otitis media in the urgent care setting. Author(s): McCracken GH Jr. Source: Annals of Emergency Medicine. 2002 April; 39(4): 413-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919528&dopt=Abstract

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Diagnostic accuracy, tympanocentesis training performance, and antibiotic selection by pediatric residents in management of otitis media. Author(s): Pichichero ME. Source: Pediatrics. 2002 December; 110(6): 1064-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456901&dopt=Abstract

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Diagnostic certainty for acute otitis media. Author(s): Rosenfeld RM. Source: International Journal of Pediatric Otorhinolaryngology. 2002 June 17; 64(2): 8995. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049821&dopt=Abstract

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Diagnostic methods for otitis media with effusion in children. Author(s): Guo YC, Shiao AS. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 August; 65(8): 372-7; Discussion 363-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455807&dopt=Abstract

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Differences in nasopharyngeal bacterial flora in children with nonsevere recurrent acute otitis media and chronic otitis media with effusion: implications for management. Author(s): Marchisio P, Claut L, Rognoni A, Esposito S, Passali D, Bellussi L, Drago L, Pozzi G, Mannelli S, Schito G, Principi N. Source: The Pediatric Infectious Disease Journal. 2003 March; 22(3): 262-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634589&dopt=Abstract

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Do parents and physicians differ in making decisions about acute otitis media? Author(s): Sorum PC, Shim J, Chasseigne G, Mullet E, Sastre MT, Stewart T, GonzalezVallejo C. Source: The Journal of Family Practice. 2002 January; 51(1): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927064&dopt=Abstract

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Does choosing a treatment depend on making a diagnosis? US and French physicians' decision making about acute otitis media. Author(s): Sorum PC, Stewart TR, Mullet E, Gonzalez-Vallejo C, Shim J, Chasseigne G, Sastre MT, Grenier B. Source: Medical Decision Making : an International Journal of the Society for Medical Decision Making. 2002 September-October; 22(5): 394-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365481&dopt=Abstract

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Does chronic otitis media cause sensorineural hearing loss? Author(s): Chasin M. Source: The Journal of Otolaryngology. 1998 August; 27(4): 246. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711524&dopt=Abstract

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Does this child have acute otitis media? Author(s): Rothman R, Owens T, Simel DL. Source: Jama : the Journal of the American Medical Association. 2003 September 24; 290(12): 1633-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506123&dopt=Abstract

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DPOAEs in young normal-hearing subjects with histories of otitis media: evidence of sub-clinical impairments. Author(s): Job A, Nottet JB. Source: Hearing Research. 2002 May; 167(1-2): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117527&dopt=Abstract

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Dural herniations, encephaloceles: an index of neglected chronic otitis media and further complications. Author(s): Manolidis S. Source: American Journal of Otolaryngology. 2002 July-August; 23(4): 203-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105784&dopt=Abstract

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Dynamics of pneumococcal nasopharyngeal carriage in children with nonresponsive acute otitis media treated with two regimens of intramuscular ceftriaxone. Author(s): Haiman T, Leibovitz E, Piglansky L, Press J, Yagupsky P, Leiberman A, Dagan R. Source: The Pediatric Infectious Disease Journal. 2002 July; 21(7): 642-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237596&dopt=Abstract

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Early versus delayed insertion of tympanostomy tubes for persistent otitis media: developmental outcomes at the age of three years in relation to prerandomization illness patterns and hearing levels. Author(s): Paradise JL, Feldman HM, Campbell TF, Dollaghan CA, Colborn DK, Bernard BS, Rockette HE, Janosky JE, Pitcairn DL, Sabo DL, Kurs-Lasky M, Smith CG. Source: The Pediatric Infectious Disease Journal. 2003 April; 22(4): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690269&dopt=Abstract

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Educational intervention for parents and healthcare providers leads to reduced antibiotic use in acute otitis media. Author(s): Smabrekke L, Berild D, Giaever A, Myrbakk T, Fuskevag A, Ericson JU, Flaegstad T, Olsvik O, Ringertz SH. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(9): 657-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374355&dopt=Abstract

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Effect of 23 valent pneumococcal polysaccharide and Haemophilus influenza conjugated vaccines on the clinical course of otitis media with effusion. Author(s): Kilic R, Safak MA, Ozdek A, Gocmen H, Kilic D, Samim E. Source: The Laryngoscope. 2002 November; 112(11): 2042-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439177&dopt=Abstract

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Effect of bacterial endotoxin and middle ear effusion on ciliary activity: implications for otitis media. Author(s): Mason PS, Adam E, Prior M, Warner JO, Randall CJ. Source: The Laryngoscope. 2002 April; 112(4): 676-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150522&dopt=Abstract

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Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study. Author(s): Veenhoven R, Bogaert D, Uiterwaal C, Brouwer C, Kiezebrink H, Bruin J, IJzerman E, Hermans P, de Groot R, Zegers B, Kuis W, Rijkers G, Schilder A, Sanders E. Source: Lancet. 2003 June 28; 361(9376): 2189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842372&dopt=Abstract

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Effect of conjugate pneumococcal vaccine on recurrent acute otitis media. Author(s): Esposito S, Principi N. Source: Lancet. 2003 September 27; 362(9389): 1080-1; Author Reply 1081. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522551&dopt=Abstract

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Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Author(s): Hoberman A, Greenberg DP, Paradise JL, Rockette HE, Lave JR, Kearney DH, Colborn DK, Kurs-Lasky M, Haralam MA, Byers CJ, Zoffel LM, Fabian IA, Bernard BS, Kerr JD. Source: Jama : the Journal of the American Medical Association. 2003 September 24; 290(12): 1608-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506120&dopt=Abstract

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Effectiveness of ototopical antibiotics for chronic suppurative otitis media in Aboriginal children: a community-based, multicentre, double-blind randomised controlled trial. Author(s): Couzos S, Lea T, Mueller R, Murray R, Culbong M. Source: The Medical Journal of Australia. 2003 August 18; 179(4): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914507&dopt=Abstract

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Effects of Allergina on the treatment of otitis media with effusions. Author(s): Jeong HJ, Hong SH, Kim SC, Park EJ, Jang CH, Kim KS, Kim HM. Source: Inflammation. 2002 April; 26(2): 89-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989792&dopt=Abstract

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Effects of large dosages of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal alpha-hemolytic streptococci, and Staphylococcus aureus in children with acute otitis media. Author(s): Ghaffar F, Muniz LS, Katz K, Smith JL, Shouse T, Davis P, McCracken GH Jr. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 May 15; 34(10): 1301-9. Epub 2002 April 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981724&dopt=Abstract

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Efficacy of intranasal virosomal influenza vaccine in the prevention of recurrent acute otitis media in children. Author(s): Marchisio P, Cavagna R, Maspes B, Gironi S, Esposito S, Lambertini L, Massimini A, Herzog C, Principi N. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 July 15; 35(2): 168-74. Epub 2002 June 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087523&dopt=Abstract

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Efficacy of single-dose azithromycin in treatment of acute otitis media in children after a baseline tympanocentesis. Author(s): Dunne MW, Khurana C, Mohs AA, Rodriguez A, Arrieta A, McLinn S, Krogstad JA, Blatter M, Schwartz R, Vargas SL, Emparanza P, Fernandez P, Gooch WM 3rd, Aspin M, Podgore J, Roine I, Blumer JL, Ehrlich GD, Chow J. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2663-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878537&dopt=Abstract

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Efficacy of surgical treatment of chronic otitis media. Author(s): Cruz OL, Kasse CA, Leonhart FD. Source: Otolaryngology and Head and Neck Surgery. 2003 February; 128(2): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601324&dopt=Abstract

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Emergence of ciprofloxacin-resistant pseudomonas in pediatric otitis media. Author(s): Jang CH, Park SY. Source: International Journal of Pediatric Otorhinolaryngology. 2003 April; 67(4): 313-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663100&dopt=Abstract

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Etiology of acute otitis media in childhood and evaluation of two different protocols of antibiotic therapy: 10 days cefaclor vs. 3 days azitromycin. Author(s): Oguz F, Unuvar E, Suoglu Y, Erdamar B, Dundar G, Katircioglu S, Sidal M. Source: International Journal of Pediatric Otorhinolaryngology. 2003 January; 67(1): 4351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560149&dopt=Abstract

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Evaluation of efficacy of nizer versus nimesulide tablets in otitis media. Author(s): Dasgupta KS, Deshpande AS, Vedi JN, Patel S. Source: J Indian Med Assoc. 2002 October; 100(10): 619. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452517&dopt=Abstract

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Evaluation of middle ear fluid in acute otitis media with Gram-stained smear. Author(s): Oguz F, Unuvar E, Dundar G. Source: The Pediatric Infectious Disease Journal. 2002 October; 21(10): 986-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394824&dopt=Abstract

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Evaluation of topical povidone-iodine in chronic suppurative otitis media. Author(s): Jaya C, Job A, Mathai E, Antonisamy B. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 October; 129(10): 1098100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568795&dopt=Abstract

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Expression of epidermal growth factor, tumor necrosis factor-alpha, and interleukin1alpha in chronic otitis media with or without cholesteatoma. Author(s): Yetiser S, Satar B, Aydin N. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 September; 23(5): 647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218613&dopt=Abstract

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Extracts from “Concise clinical evidence”: Chronic suppurative otitis media. Author(s): Acuin J. Source: Bmj (Clinical Research Ed.). 2002 November 16; 325(7373): 1159; Discussion 1159. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433769&dopt=Abstract

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Facial nerve paralysis due to chronic otitis media. Author(s): Yetiser S, Tosun F, Kazkayasi M. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 July; 23(4): 580-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170164&dopt=Abstract

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Facial nerve paralysis in acute otitis media: cause and management revisited. Author(s): Joseph EM, Sperling NM. Source: Otolaryngology and Head and Neck Surgery. 1998 May; 118(5): 694-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9591875&dopt=Abstract

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Facial nerve paralysis in chronic suppurative otitis media: Ankara Numune Hospital experience. Author(s): Altuntas A, Unal A, Aslan A, Ozcan M, Kurkcuoglu S, Nalca Y. Source: Auris, Nasus, Larynx. 1998 May; 25(2): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9673730&dopt=Abstract

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Facial palsy in acute otitis media. Author(s): Ellefsen B, Bonding P. Source: Clinical Otolaryngology and Allied Sciences. 1996 October; 21(5): 393-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932940&dopt=Abstract

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Facial paralysis secondary to acute otitis media. Author(s): White N, McCans KM. Source: Pediatric Emergency Care. 2000 October; 16(5): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063365&dopt=Abstract

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Factors affecting the results of nonsurgical treatment of secretory otitis media in adults. Author(s): Lesinskas E. Source: Auris, Nasus, Larynx. 2003 February; 30(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589843&dopt=Abstract

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Factors associated with poor outcome in children with acute otitis media. Author(s): Monobe H, Ishibashi T, Fujishiro Y, Shinogami M, Yano J. Source: Acta Oto-Laryngologica. 2003 June; 123(5): 564-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875576&dopt=Abstract

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Factors associated with the development of recurrent acute otitis media--the significance of choosing the right and accurate dependent and independent variables in the multivariate analysis. Author(s): Jero J, Kentala E, Karma P. Source: Acta Otolaryngol Suppl. 2000; 543: 67-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908981&dopt=Abstract

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Failure of antibiotic therapy in acute otitis media. Author(s): Babin E, Lemarchand V, Moreau S, Goullet de Rugy M, Valdazo A, Bequignon A. Source: The Journal of Laryngology and Otology. 2003 March; 117(3): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648370&dopt=Abstract

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Failure of grommet insertion in post-irradiation otitis media with effusion. Author(s): Chen CY, Young YH, Hsu WC, Hsu MM. Source: The Annals of Otology, Rhinology, and Laryngology. 2001 August; 110(8): 746-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510732&dopt=Abstract

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Feasibility survey for a study on selective antibiotic management of acute otitis media. Author(s): Yen K, Walsh-Kelly C, Hennes H. Source: Wmj. 2001; 100(8): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685298&dopt=Abstract

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Five vs. ten days of antibiotic therapy for acute otitis media in young children. Author(s): Cohen R, Levy C, Boucherat M, Langue J, Autret E, Gehanno P, de La Rocque F. Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5): 458-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10819344&dopt=Abstract

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Five-day cefdinir course vs. ten-day cefprozil course for treatment of acute otitis media. Author(s): Block SL, Kratzer J, Nemeth MA, Tack KJ. Source: The Pediatric Infectious Disease Journal. 2000 December; 19(12 Suppl): S147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144396&dopt=Abstract

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Five-day twice daily cefdinir therapy for acute otitis media: microbiologic and clinical efficacy. Author(s): Block SL, Hedrick JA, Kratzer J, Nemeth MA, Tack KJ. Source: The Pediatric Infectious Disease Journal. 2000 December; 19(12 Suppl): S153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144397&dopt=Abstract

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Five-day versus ten-day treatment of acute otitis media with cefprozil. Author(s): Kafetzis DA, Astra H, Mitropoulos L. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1997 April; 16(4): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9177961&dopt=Abstract

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Flaws in design and conduct of clinical trials in acute otitis media. Author(s): Dagan R, McCracken GH Jr. Source: The Pediatric Infectious Disease Journal. 2002 October; 21(10): 894-902. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394809&dopt=Abstract

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Foreign body neonatal otitis media in infants. Author(s): Palva T, Northrop C, Ramsay H. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2001 July; 22(4): 433-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449095&dopt=Abstract

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Foreign-body-induced otitis media: a case report. Author(s): Lin CC, Ho KY, Wang LF, Kuo WR. Source: Kaohsiung J Med Sci. 2002 November; 18(11): 585-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513023&dopt=Abstract

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Functional analysis of episodic self-injury correlated with recurrent otitis media. Author(s): O'Reilly MF. Source: J Appl Behav Anal. 1997 Spring; 30(1): 165-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9103992&dopt=Abstract

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Fundamental basis for rational therapeutics in acute otitis media. Author(s): Blumer JL. Source: The Pediatric Infectious Disease Journal. 1999 December; 18(12): 1130-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608645&dopt=Abstract

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Galbreath technique: a manipulative treatment for otitis media revisited. Author(s): Pratt-Harrington D. Source: J Am Osteopath Assoc. 2000 October; 100(10): 635-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105452&dopt=Abstract

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Gas exchange function of the middle ear in patients with otitis media with effusion. Author(s): Tanabe M, Takahashi H, Honjo I, Hasebe S. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 1997; 254(9-10): 453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9438116&dopt=Abstract

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Generalisability of clinical trials in otitis media with effusion. Author(s): Rovers MM, Zielhuis GA, Bennett K, Haggard M. Source: International Journal of Pediatric Otorhinolaryngology. 2001 July 30; 60(1): 2940. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434951&dopt=Abstract

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Genetic alteration of penicillin non-susceptible Streptococcus pneumoniae observed throughout recurrence of acute otitis media detected by amplified fragment length polymorphism analysis. Author(s): Sugata K, Fukushima K, Ogawa T, Nakashima T, Sugata A, Kasai N, Gunduz M, Ueki Y, Nishizaki K. Source: Acta Medica Okayama. 2001 June; 55(3): 167-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434429&dopt=Abstract

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Gland formation in otitis media. An ultrastructural study in humans. Author(s): Goycoolea MV. Source: Acta Oto-Laryngologica. 2001 January; 121(2): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349774&dopt=Abstract

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Gradenigo's syndrome--a rare complication of otitis media. Author(s): Jagadeesan P, Madeswaran K, Thiruppathy SP, Kalairajan D, Inbasekaran V. Source: J Indian Med Assoc. 2002 November; 100(11): 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797641&dopt=Abstract

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Granuloma inguinale (donovanosis): an unusual cause of otitis media and mastoiditis in children. Author(s): Govender D, Naidoo K, Chetty R. Source: American Journal of Clinical Pathology. 1997 November; 108(5): 510-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9353089&dopt=Abstract

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Group-A streptococcal meningitis in an adult, secondary to purulent otitis media. Author(s): Cohen-Kerem R, Lavon H. Source: The Journal of Laryngology and Otology. 2002 July; 116(7): 541-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238676&dopt=Abstract

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Guidelines for managing chronic otitis media with effusion. Author(s): Magit AE. Source: The Western Journal of Medicine. 1995 August; 163(2): 153. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7571563&dopt=Abstract

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Hearing aids versus ventilation tubes in persistent otitis media with effusion: a survey of clinical practice. Author(s): Ahmmed AU, Curley JW, Newton VE, Mukherjee D. Source: The Journal of Laryngology and Otology. 2001 April; 115(4): 274-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11276327&dopt=Abstract

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Hearing deficits in young adults who had a history of otitis media in childhood: use of personal stereos had no effect on hearing. Author(s): de Beer BA, Graamans K, Snik AF, Ingels K, Zielhuis GA. Source: Pediatrics. 2003 April; 111(4 Pt 1): E304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671143&dopt=Abstract

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Hearing loss due to mannosidosis and otitis media with effusion. A case report and review of audiological assessments in children with otitis media with effusion. Author(s): Ahmmed AU, O'Halloran SM, Roland NJ, Starkey M, Wraith JE. Source: The Journal of Laryngology and Otology. 2003 April; 117(4): 307-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816222&dopt=Abstract

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Heat myringotomy for the treatment of serous otitis media. Author(s): Goode RL, Schulz W. Source: Otolaryngology and Head and Neck Surgery. 1982 November-December; 90(6): 764-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994426&dopt=Abstract

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Heritability of symptom domains in otitis media: a longitudinal study of 1,373 twin pairs. Author(s): Rovers M, Haggard M, Gannon M, Koeppen-Schomerus G, Plomin R. Source: American Journal of Epidemiology. 2002 May 15; 155(10): 958-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994236&dopt=Abstract

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High incidence of Alloiococcus otitis in otitis media with effusion. Author(s): Hendolin PH, Karkkainen U, Himi T, Markkanen A, Ylikoski J. Source: The Pediatric Infectious Disease Journal. 1999 October; 18(10): 860-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530580&dopt=Abstract

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High incidence of complications encountered in chronic otitis media surgery in a U.S. metropolitan public hospital. Author(s): Greenberg JS, Manolidis S. Source: Otolaryngology and Head and Neck Surgery. 2001 December; 125(6): 623-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743464&dopt=Abstract

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High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae. Author(s): Cody AJ, Field D, Feil EJ, Stringer S, Deadman ME, Tsolaki AG, Gratz B, Bouchet V, Goldstein R, Hood DW, Moxon ER. Source: Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2003 May; 3(1): 57-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797973&dopt=Abstract

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High-dose amoxicillin in new guidelines for treatment of otitis media in children. Author(s): Reed MD. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 November 15; 56(22): 2351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10582834&dopt=Abstract

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High-frequency hearing loss and wideband middle ear impedance in children with otitis media histories. Author(s): Margolis RH, Saly GL, Hunter LL. Source: Ear and Hearing. 2000 June; 21(3): 206-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890728&dopt=Abstract

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Histopathological changes of chorda tympani in chronic otitis media. Author(s): Gedikli O, Dogru H, Aydin G, Tuz M, Uygur K, Sari A. Source: The Laryngoscope. 2001 April; 111(4 Pt 1): 724-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359147&dopt=Abstract

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Histopathology of experimental acute otitis media caused by various bacteria. An investigation on goblet cell density, polyp- and adhesion formation, bone modeling dynamics and the effect of antibiotic treatment. Author(s): Caye-Thomasen P. Source: Apmis. Supplementum. 2001; (104): 1-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692745&dopt=Abstract

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Home monitoring of the middle ear system with spectral gradient acoustic reflectometry: distinguishing acute otitis media from upper respiratory infection. Author(s): Barnett ED, Cabral HJ, Klein JO. Source: The Pediatric Infectious Disease Journal. 2000 April; 19(4): 360-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783033&dopt=Abstract

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Homeopathic treatment of acute otitis media in children: a preliminary randomized placebo-controlled trial. Author(s): Jacobs J, Springer DA, Crothers D. Source: The Pediatric Infectious Disease Journal. 2001 February; 20(2): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11224838&dopt=Abstract

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Homeopathy in acute otitis media in children: treatment effect or spontaneous resolution? Author(s): Frei H, Thurneysen A. Source: Br Homeopath J. 2001 October; 90(4): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680801&dopt=Abstract

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Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media. Author(s): Bouchet V, Hood DW, Li J, Brisson JR, Randle GA, Martin A, Li Z, Goldstein R, Schweda EK, Pelton SI, Richards JC, Moxon ER. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 22; 100(15): 8898-903. Epub 2003 Jul 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855765&dopt=Abstract

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Household transmission of Streptococcus pneumoniae among siblings with acute otitis media. Author(s): Shimada J, Yamanaka N, Hotomi M, Suzumoto M, Sakai A, Ubukata K, Mitsuda T, Yokota S, Faden H. Source: Journal of Clinical Microbiology. 2002 May; 40(5): 1851-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980976&dopt=Abstract

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How does a “wait and see” approach to prescribing antibiotics for acute otitis media (AOM) compare with immediate antibiotic treatment? Author(s): Bascelli LM, Losh DP. Source: The Journal of Family Practice. 2001 May; 50(5): 469. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350715&dopt=Abstract

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How does endotoxin trigger inflammation in otitis media with effusion? Author(s): Schousboe LP, Ovesen T, Eckhardt L, Rasmussen LM, Pedersen CB. Source: The Laryngoscope. 2001 February; 111(2): 297-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210878&dopt=Abstract

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Hyper immunoglobulin-E syndrome: a case with chronic ear draining mimicking polypoid otitis media. Author(s): Gorur K, Ozcan C, Unal M, Akbas Y, Vayisoglu Y. Source: International Journal of Pediatric Otorhinolaryngology. 2003 April; 67(4): 409-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663115&dopt=Abstract

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Identification of the lipooligosaccharide biosynthesis gene lic2B as a putative virulence factor in strains of nontypeable Haemophilus influenzae that cause otitis media. Author(s): Pettigrew MM, Foxman B, Marrs CF, Gilsdorf JR. Source: Infection and Immunity. 2002 July; 70(7): 3551-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065495&dopt=Abstract

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IL-5 and eotaxin levels in middle ear effusion and blood from asthmatics with otitis media with effusion. Author(s): Nonaka M, Fukumoto A, Ozu C, Mokuno E, Baba S, Pawankar R, Yagi T. Source: Acta Oto-Laryngologica. 2003 April; 123(3): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737295&dopt=Abstract

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Immunologic aspects of otitis media. Author(s): Bernstein JM. Source: Curr Allergy Asthma Rep. 2002 July; 2(4): 309-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044266&dopt=Abstract

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Impact of the pneumococcal conjugate vaccine on otitis media. Author(s): Fireman B, Black SB, Shinefield HR, Lee J, Lewis E, Ray P. Source: The Pediatric Infectious Disease Journal. 2003 January; 22(1): 10-6. Erratum In: Pediatr Infect Dis J. 2003 February; 22(2): 163. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544402&dopt=Abstract

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Implications of the AHRQ evidence report on acute otitis media. Author(s): Rosenfeld RM, Casselbrant ML, Hannley MT. Source: Otolaryngology and Head and Neck Surgery. 2001 November; 125(5): 440-8; Discussion 439. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700439&dopt=Abstract

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Importance of respiratory viruses in acute otitis media. Author(s): Heikkinen T, Chonmaitree T. Source: Clinical Microbiology Reviews. 2003 April; 16(2): 230-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692096&dopt=Abstract

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In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media. Author(s): Yagupsky P, Katz O, Peled N, Dagan R. Source: Chemotherapy. 2001 September-October; 47(5): 354-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561138&dopt=Abstract

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In vitro study of IL-8 and goblet cells: possible role of IL-8 in the aetiology of otitis media with effusion. Author(s): Smirnova MG, Birchall JP, Pearson JP. Source: Acta Oto-Laryngologica. 2002 March; 122(2): 146-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936905&dopt=Abstract

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Incidence of adenovirus and respiratory syncytial virus in chronic otitis media with effusion using the polymerase chain reaction. Author(s): Shaw CB, Obermyer N, Wetmore SJ, Spirou GA, Farr RW. Source: Otolaryngology and Head and Neck Surgery. 1995 September; 113(3): 234-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7675483&dopt=Abstract

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Increased antimicrobial resistance in organisms recovered from otitis media with effusion. Author(s): Brook I, Yocum P, Shah K, Feldman B, Epstein S. Source: The Journal of Laryngology and Otology. 2003 June; 117(6): 449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818052&dopt=Abstract

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Increasing antibiotic resistance: its effect on the therapy for otitis media. Author(s): Sagraves R. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 2002 March-April; 16(2): 79-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904642&dopt=Abstract

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Increasing prevalence of recurrent otitis media among children in the United States. Author(s): Lanphear BP, Byrd RS, Auinger P, Hall CB. Source: Pediatrics. 1997 March; 99(3): E1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9099766&dopt=Abstract

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Induction of mucous cell metaplasia by tumor necrosis factor alpha in rat middle ear: the pathological basis for mucin hyperproduction in mucoid otitis media. Author(s): Kawano H, Haruta A, Tsuboi Y, Kim Y, Schachern PA, Paparella MM, Lin J. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 May; 111(5 Pt 1): 41522. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018326&dopt=Abstract

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Induction of mucous cell metaplasia in the middle ear of rats using a three-step method: an improved model for otitis media with mucoid effusion. Author(s): Tsuboi Y, Kim Y, Giebink GS, Le C, Paparella MM, Chen N, Schachern PA, Juhn SK, Lin J. Source: Acta Oto-Laryngologica. 2002 March; 122(2): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936906&dopt=Abstract

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Influenza virus vaccines in children and their impact on the incidence of otitis media. Author(s): Rafei K. Source: Seminars in Pediatric Infectious Diseases. 2002 April; 13(2): 129-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122951&dopt=Abstract

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Infrared transtympanic temperature measurement and otitis media with effusion. Author(s): Cochrane Database Syst Rev. 2002;(1):CD001727 Source: International Journal of Pediatric Otorhinolaryngology. 2001 July 2; 59(3): 195200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11869604

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Is gastric reflux a cause of otitis media with effusion in children? Author(s): Tasker A, Dettmar PW, Panetti M, Koufman JA, P Birchall J, Pearson JP. Source: The Laryngoscope. 2002 November; 112(11): 1930-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439157&dopt=Abstract

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Is pacifier use a risk factor for otitis media? Author(s): Post JC, Goessier MC. Source: Lancet. 2001 March 17; 357(9259): 823-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11265948&dopt=Abstract

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Is secretory otitis media a single disease entity? Author(s): Sade J, Russo E, Fuchs C, Cohen D. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 April; 112(4): 342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12731629&dopt=Abstract

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Is there a relationship between proximity to industry and the occurrence of otitis media with effusion in school entrant children? Author(s): Holtby I, Elliott K, Kumar U. Source: Public Health. 1997 March; 111(2): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9090283&dopt=Abstract

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JAMA patient page. Acute otitis media. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 September 24; 290(12): 1666. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506125&dopt=Abstract

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Knowledge and attitudes about otitis media risk: implications for prevention. Author(s): Daly KA, Selvius RE, Lindgren B. Source: Pediatrics. 1997 December; 100(6): 931-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9374559&dopt=Abstract

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Labyrinthine fistula after cholesteatomatous chronic otitis media. Author(s): Gersdorff MC, Nouwen J, Decat M, Degols JC, Bosch P. Source: The American Journal of Otology. 2000 January; 21(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10651432&dopt=Abstract

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Labyrinthine fistula: a complication of chronic suppurative otitis media. Author(s): Grewal DS, Hathiram BT, Dwivedi A, Kumar L, Sheth K, Srivastava S. Source: The Journal of Laryngology and Otology. 2003 May; 117(5): 353-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803784&dopt=Abstract

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Labyrinthine involvement and multiple perforations of the tympanic membrane in acute otitis media due to group A streptococci. Author(s): Kanazawa T, Hagiwara H, Kitamura K. Source: The Journal of Laryngology and Otology. 2000 January; 114(1): 47-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789411&dopt=Abstract

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Labyrinthitis in chronic otitis media. Author(s): Siwiec H, Klatka J, Szymanski M, Trojanowski P. Source: Ann Univ Mariae Curie Sklodowska [med]. 2002; 57(2): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898830&dopt=Abstract

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Lack of association between mannose-binding lectin, acute otitis media and early Epstein-Barr virus infection among children in Greenland. Author(s): Homoe P, Madsen HO, Sandvej K, Koch A, Garred P. Source: Scandinavian Journal of Infectious Diseases. 1999; 31(4): 363-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10528874&dopt=Abstract

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Language, speech sound production, and cognition in three-year-old children in relation to otitis media in their first three years of life. Author(s): Paradise JL, Dollaghan CA, Campbell TF, Feldman HM, Bernard BS, Colborn DK, Rockette HE, Janosky JE, Pitcairn DL, Sabo DL, Kurs-Lasky M, Smith CG. Source: Pediatrics. 2000 May; 105(5): 1119-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790473&dopt=Abstract

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Laser assisted myringotomy for otitis media with effusion in children. Author(s): Clin Evid. 2002 Dec;(8):251-61 Source: Orl Head Neck Nurs. 2002 Summer; 20(3): 11-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603882

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Laser-assisted myringotomy for otitis media: a feasibility study with short-term followup. Author(s): Reilly JS, Deutsch ES, Cook S. Source: Ear, Nose, & Throat Journal. 2000 August; 79(8): 650-2, 654-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969476&dopt=Abstract

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Lasting effects of otitis media with effusion on language skills and listening performance. Author(s): Klausen O, Moller P, Holmefjord A, Reisaeter S, Asbjornsen A. Source: Acta Otolaryngol Suppl. 2000; 543: 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908983&dopt=Abstract

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Lateral sinus thrombosis after untreated otitis media. A clinical problem--again? Author(s): Spandow O, Gothefors L, Fagerlund M, Kristensen B, Holm S. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2000; 257(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10664036&dopt=Abstract

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Laterally hypertrophic adenoids as a contributing factor in otitis media. Author(s): Wright ED, Pearl AJ, Manoukian JJ. Source: International Journal of Pediatric Otorhinolaryngology. 1998 October 15; 45(3): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9865437&dopt=Abstract

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Lemon-flavored cod liver oil and a multivitamin-mineral supplement for the secondary prevention of otitis media in young children: pilot research. Author(s): Linday LA, Dolitsky JN, Shindledecker RD, Pippenger CE. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 July; 111(7 Pt 1): 64252. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126022&dopt=Abstract

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Long-term communication deficiencies in children with otitis media during their first year of life. Author(s): Ruben RJ, Wallace IF, Gravel J. Source: Acta Oto-Laryngologica. 1997 March; 117(2): 206-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9105449&dopt=Abstract

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Long-term effects of chronic otitis media on binaural hearing in children. Author(s): Hall JW 3rd, Grose JH, Pillsbury HC. Source: Archives of Otolaryngology--Head & Neck Surgery. 1995 August; 121(8): 847-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7619408&dopt=Abstract

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Long-term observation on hearing change in patients with chronic otitis media. Author(s): Sakagami M, Maeda A, Node M, Sone M, Mishiro Y. Source: Auris, Nasus, Larynx. 2000 April; 27(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733138&dopt=Abstract

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Long-term post-operative follow-up of patients with chronic otitis media. Does it make sense? Author(s): Vartiainen E, Virtaniemi J, Vartiainen J. Source: Clinical Otolaryngology and Allied Sciences. 1995 August; 20(4): 352-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8548970&dopt=Abstract

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Loracarbef versus clarithromycin in children with acute otitis media with effusion. Author(s): Gooch WM 3rd, Adelglass J, Kelsey DK, Masica D, Johns D Jr, Weinberg BC. Source: Clinical Therapeutics. 1999 April; 21(4): 711-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10363736&dopt=Abstract

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Low cord blood pneumococcal antibody concentrations predict more episodes of otitis media. Author(s): Becken ET, Daly KA, Lindgren BR, Meland MH, Giebink GS. Source: Archives of Otolaryngology--Head & Neck Surgery. 2001 May; 127(5): 517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346426&dopt=Abstract

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Low cord blood type 14 pneumococcal IgG1 but not IgG2 antibody predicts early infant otitis media. Author(s): Lockhart NJ, Daly KA, Lindgren BR, Meland M, Le CT, Giebink GS. Source: The Journal of Infectious Diseases. 2000 June; 181(6): 1979-82. Epub 2000 May 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10837178&dopt=Abstract

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Lymphocyte subpopulations in hypertrophied adenoid in children with otitis media with effusion. Author(s): Wysocka J, Hassmann E, Kasprzycka E, Musiatowicz M, Lipska A. Source: Rocz Akad Med Bialymst. 2002; 47: 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533952&dopt=Abstract

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Management of acute otitis media. Author(s): Marcy SM. Source: The Pediatric Infectious Disease Journal. 2003 July; 22(7): 673-4; Author Reply 674. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867849&dopt=Abstract

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Measurement of cefaclor and amoxicillin-clavulanic acid levels in middle-ear fluid in patients with acute otitis media. Author(s): Scaglione F, Caronzolo D, Pintucci JP, Fraschini F. Source: Antimicrobial Agents and Chemotherapy. 2003 September; 47(9): 2987-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937009&dopt=Abstract

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Medical and surgical management of otitis media in children. Author(s): Perkins JA. Source: Otolaryngologic Clinics of North America. 2002 August; 35(4): 811-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487083&dopt=Abstract

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Microbiology and management of chronic suppurative otitis media in children. Author(s): Brook I. Source: Journal of Tropical Pediatrics. 2003 August; 49(4): 196-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929878&dopt=Abstract

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Microbiology of chronic suppurative otitis media in Singapore. Author(s): Loy AH, Tan AL, Lu PK. Source: Singapore Med J. 2002 June; 43(6): 296-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380726&dopt=Abstract

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Middle ear fluid histamine and leukotriene B4 in acute otitis media: effect of antihistamine or corticosteroid treatment. Author(s): McCormick DP, Saeed K, Uchida T, Baldwin CD, Deskin R, Lett-Brown MA, Heikkinen T, Chonmaitree T. Source: International Journal of Pediatric Otorhinolaryngology. 2003 March; 67(3): 22130. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633920&dopt=Abstract

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Modern management of acute otitis media. Author(s): Weber SM, Grundfast KM. Source: Pediatric Clinics of North America. 2003 April; 50(2): 399-411. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809330&dopt=Abstract

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Mucin gene expression in the effusions of otitis media with effusion. Author(s): Takeuchi K, Yagawa M, Ishinaga H, Kishioka C, Harada T, Majima Y. Source: International Journal of Pediatric Otorhinolaryngology. 2003 January; 67(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560150&dopt=Abstract

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Multinational study of pneumococcal serotypes causing acute otitis media in children. Author(s): Hausdorff WP, Yothers G, Dagan R, Kilpi T, Pelton SI, Cohen R, Jacobs MR, Kaplan SL, Levy C, Lopez EL, Mason EO Jr, Syriopoulou V, Wynne B, Bryant J. Source: The Pediatric Infectious Disease Journal. 2002 November; 21(11): 1008-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442021&dopt=Abstract

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Multiplex nested reverse transcription-polymerase chain reaction for respiratory viruses in acute otitis media. Author(s): Ishibashi T, Monobe H, Nomura Y, Shinogami M, Yano J. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 March; 112(3): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656418&dopt=Abstract

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Myringoplasty for chronic otitis media. Author(s): Goyal N, Kakkar V, Goyal P, Yadav SP. Source: Indian J Pediatr. 2002 March; 69(3): 223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003296&dopt=Abstract

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Nasopharyngeal carriage of anaerobes during health and acute otitis media by two years of age. Author(s): Kononen E, Syrjanen R, Takala A, Jousimies-Somer H. Source: Diagnostic Microbiology and Infectious Disease. 2003 July; 46(3): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867091&dopt=Abstract

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Nasopharyngeal carriage of drug-resistant Streptococcus pneumoniae in children with acute otitis media evaluated by polymerase chain reaction-based genotyping of penicillin-binding proteins. Author(s): Hotomi M, Yamanaka N, Faden H, Shimada J, Suzumoto M, Sakai A, Saito T, Kuki K. Source: Acta Oto-Laryngologica. 2002 January; 122(1): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876602&dopt=Abstract

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National differences in incidence of acute mastoiditis: relationship to prescribing patterns of antibiotics for acute otitis media? Author(s): Van Zuijlen DA, Schilder AG, Van Balen FA, Hoes AW. Source: The Pediatric Infectious Disease Journal. 2001 February; 20(2): 140-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11224830&dopt=Abstract

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Natural development of antibodies to pneumococcal capsular polysaccharides depends on the serotype: association with pneumococcal carriage and acute otitis media in young children. Author(s): Soininen A, Pursiainen H, Kilpi T, Kayhty H. Source: The Journal of Infectious Diseases. 2001 September 1; 184(5): 569-76. Epub 2001 August 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494163&dopt=Abstract

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Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media. Author(s): Rapola S, Jantti V, Haikala R, Syrjanen R, Carlone GM, Sampson JS, Briles DE, Paton JC, Takala AK, Kilpi TM, Kayhty H. Source: The Journal of Infectious Diseases. 2000 October; 182(4): 1146-52. Epub 2000 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979911&dopt=Abstract

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Natural history of untreated otitis media. Author(s): Rosenfeld RM, Kay D. Source: The Laryngoscope. 2003 October; 113(10): 1645-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520089&dopt=Abstract

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Negative pressure tympanograms in children less than 2 years of age--different bacterial findings in otitis media by tympanometric results. Author(s): Palmu A, Syrjanen R, Kilpi T, Pursiainen H, Puhakka H, Rahko T, Herva E, Takala A. Source: International Journal of Pediatric Otorhinolaryngology. 2001 October 19; 61(1): 61-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576632&dopt=Abstract

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Non-cholesteatomatous suppurative otitis media: facial nerve palsy in an immunocompromised patient. Author(s): Hartley C, Saeed SR, Lyons TJ. Source: The Journal of Laryngology and Otology. 1995 August; 109(8): 755-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561501&dopt=Abstract

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Nonimmune strategies for prevention of otitis media. Author(s): Klein JO. Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5 Suppl): S89-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821477&dopt=Abstract

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Nonsurgical management of surgical otitis media with effusion. Author(s): Rosenfeld RM. Source: The Journal of Laryngology and Otology. 1995 September; 109(9): 811-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7494110&dopt=Abstract

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Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children. Author(s): Butler CC, Van Der Voort JH. Source: Cochrane Database Syst Rev. 2002; (4): Cd001935. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519563&dopt=Abstract

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Osteopathic manipulation to prevent otitis media--does it work? Author(s): Pichichero ME. Source: Archives of Pediatrics & Adolescent Medicine. 2003 September; 157(9): 852-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963587&dopt=Abstract

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Otitis media and tympanostomy tube insertion during the first three years of life: developmental outcomes at the age of four years. Author(s): Paradise JL, Dollaghan CA, Campbell TF, Feldman HM, Bernard BS, Colborn DK, Rockette HE, Janosky JE, Pitcairn DL, Kurs-Lasky M, Sabo DL, Smith CG. Source: Pediatrics. 2003 August; 112(2): 265-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897272&dopt=Abstract

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Otitis media in children: use of diagnostic tools by family practice residents. Author(s): MacClements JE, Parchman M, Passmore C. Source: Family Medicine. 2002 September; 34(8): 598-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269536&dopt=Abstract

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Otitis media in early childhood in relation to children's school-age language and academic skills. Author(s): Roberts JE, Burchinal MR, Zeisel SA. Source: Pediatrics. 2002 October; 110(4): 696-706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359782&dopt=Abstract

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Otitis media with effusion: an update. Author(s): Pang KP, Ang AH, Tan HK. Source: Med J Malaysia. 2002 September; 57(3): 376-82; Quiz 383. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440282&dopt=Abstract

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Otitis media. Author(s): Gupta BD, Singh A. Source: Indian J Pediatr. 2001 July; 68 Suppl 3: S24-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980456&dopt=Abstract

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Otitis media. Author(s): Wald ER. Source: The New England Journal of Medicine. 2003 January 23; 348(4): 363; Author Reply 363. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540656&dopt=Abstract

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Otitis media: current treatment issues & trends. Author(s): McAdams CC, Heller C, Calandra LM. Source: Adv Nurse Pract. 2001 February; 9(2): 69-70, 73-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416058&dopt=Abstract

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Otitis media: old problem, new problem. Author(s): Shulman ST. Source: Pediatric Annals. 2002 December; 31(12): 767-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503433&dopt=Abstract

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Pathogenic agents of chronic suppurative otitis media in Ilorin, Nigeria. Author(s): Nwabuisi C, Ologe FE. Source: East Afr Med J. 2002 April; 79(4): 202-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625677&dopt=Abstract

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Pathogens in acute otitis media--impact of intermittent penicillin V prophylaxis on infant nasopharyngeal flora. Author(s): Fogle-Hansson M, White P, Hermansson A. Source: International Journal of Pediatric Otorhinolaryngology. 2003 May; 67(5): 511-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697353&dopt=Abstract

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Pediatric bilateral facial nerve palsy secondary to acute otitis media. Author(s): Ochi K, Miyamoto Y, Ohashi T. Source: Auris, Nasus, Larynx. 2003 February; 30 Suppl: S97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543170&dopt=Abstract

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Physical examination for otitis media. Author(s): Roddey OF Jr, Hoover HA, Earle R Jr. Source: The Pediatric Infectious Disease Journal. 2003 July; 22(7): 673. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867848&dopt=Abstract

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Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal capsular polysaccharides in children. Author(s): Simell B, Kilpi TM, Kayhty H. Source: The Journal of Infectious Diseases. 2002 October 15; 186(8): 1106-14. Epub 2002 September 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355361&dopt=Abstract

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Pneumococcal conjugate vaccine for acute otitis media--yes or no? Author(s): Peltola H, Schmitt J, Booy R. Source: Lancet. 2003 June 28; 361(9376): 2170-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842365&dopt=Abstract

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Preliminary results with the use of AlloDerm in chronic otitis media. Author(s): Fayad JN, Baino T, Parisier SC. Source: The Laryngoscope. 2003 July; 113(7): 1228-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838024&dopt=Abstract

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Prevention of otitis media by adenoidectomy in children younger than 2 years. Author(s): Mattila PS, Joki-Erkkila VP, Kilpi T, Jokinen J, Herva E, Puhakka H. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 February; 129(2): 1638. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578443&dopt=Abstract

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Prevention of otitis media caused by viral upper respiratory tract infection: vaccines, antivirals, and other approaches. Author(s): Doyle WJ, Alper CM. Source: Curr Allergy Asthma Rep. 2003 July; 3(4): 326-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791210&dopt=Abstract

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Protective efficacy of a second pneumococcal conjugate vaccine against pneumococcal acute otitis media in infants and children: randomized, controlled trial of a 7-valent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine in 1666 children. Author(s): Kilpi T, Ahman H, Jokinen J, Lankinen KS, Palmu A, Savolainen H, Gronholm M, Leinonen M, Hovi T, Eskola J, Kayhty H, Bohidar N, Sadoff JC, Makela PH; Finnish Otitis Media Study Group. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 November 1; 37(9): 1155-64. Epub 2003 October 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557958&dopt=Abstract

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Quality improvement: an ACQIP exercise on the management of otitis media. Author(s): Sebring RH. Source: Pediatrics in Review / American Academy of Pediatrics. 1996 July; 17(7): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8710724&dopt=Abstract

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Quality of life for children with otitis media. Author(s): Rosenfeld RM, Goldsmith AJ, Tetlus L, Balzano A. Source: Archives of Otolaryngology--Head & Neck Surgery. 1997 October; 123(10): 104954. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339979&dopt=Abstract

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Quality-of-life outcomes after surgical intervention for otitis media. Author(s): Richards M, Giannoni C. Source: Archives of Otolaryngology--Head & Neck Surgery. 2002 July; 128(7): 776-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117333&dopt=Abstract

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Quinolone ear drops for chronic otitis media. They are safer and more effective than aminoglycosides. Author(s): Ghosh S, Panarese A, Parker AJ, Bull PD. Source: Bmj (Clinical Research Ed.). 2000 July 15; 321(7254): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10894673&dopt=Abstract

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Radio-tympano-sinu-orthesis with 186Re-colloid: a new treatment modality for chronic otitis media and paranasal mucositis. Author(s): Kampen WU, Godbersen GS, Czech N, Besch OF, Brenner W, Henze E. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 April; 44(4): 559-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679400&dopt=Abstract

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Recurrent otitis media in children. Author(s): Mascitelli L, Pezzetta F. Source: Jama : the Journal of the American Medical Association. 2003 March 19; 289(11): 1383; Author Reply 1384-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636458&dopt=Abstract

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Recurrent otitis media in children. Author(s): Gillespie MB. Source: Jama : the Journal of the American Medical Association. 2003 March 19; 289(11): 1383-4; Author Reply 1384-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636457&dopt=Abstract

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Recurrent otitis media in children. Author(s): Jackson AB, Kadota R, Gordon J. Source: Jama : the Journal of the American Medical Association. 2003 March 19; 289(11): 1382-3; Author Reply 1384-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636456&dopt=Abstract

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Recurrent otitis media in children. Author(s): Lee KG. Source: Jama : the Journal of the American Medical Association. 2003 March 19; 289(11): 1384; Author Reply 1384-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636455&dopt=Abstract

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Resistant bacteria in the adenoid tissues of children with otitis media with effusion. Author(s): Karlidag T, Demirdag K, Kaygusuz I, Ozden M, Yalcin S, Ozturk L. Source: International Journal of Pediatric Otorhinolaryngology. 2002 May 31; 64(1): 3540. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020912&dopt=Abstract

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Response-shift bias and parent-reported quality of life in children with otitis media. Author(s): Timmerman AA, Anteunis LJ, Meesters CM. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 September; 129(9): 987-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975273&dopt=Abstract

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Review of randomized controlled trials on pneumococcal vaccination for prevention of otitis media. Author(s): Straetemans M, Sanders EA, Veenhoven RH, Schilder AG, Damoiseaux RA, Zielhuis GA. Source: The Pediatric Infectious Disease Journal. 2003 June; 22(6): 515-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799508&dopt=Abstract

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Risk factors for the development of otitis media. Author(s): Dhooge IJ. Source: Curr Allergy Asthma Rep. 2003 July; 3(4): 321-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791209&dopt=Abstract

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Role of respiratory viruses in children with acute otitis media. Author(s): Monobe H, Ishibashi T, Nomura Y, Shinogami M, Yano J. Source: International Journal of Pediatric Otorhinolaryngology. 2003 July; 67(7): 801-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791457&dopt=Abstract

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Screening children in the first four years of life to undergo early treatment for otitis media with effusion. Author(s): Butler CC, van der Linden MK, MacMillan H, van der Wouden JC. Source: Cochrane Database Syst Rev. 2003; (2): Cd004163. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804500&dopt=Abstract

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Sensorineural hearing loss in chronic otitis media. Author(s): Papp Z, Rezes S, Jokay I, Sziklai I. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 March; 24(2): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621323&dopt=Abstract

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Sequelae of otitis media with effusion among children with cleft lip and/or cleft palate. Author(s): Sheahan P, Blayney AW, Sheahan JN, Earley MJ. Source: Clinical Otolaryngology and Allied Sciences. 2002 December; 27(6): 494-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472518&dopt=Abstract

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Shortened course of antibacterial therapy for acute otitis media. Author(s): Ovetchkine P, Cohen R. Source: Paediatric Drugs. 2003; 5(2): 133-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529165&dopt=Abstract

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Suppurative complications of acute otitis media in the era of antibiotic resistance. Author(s): Zapalac JS, Billings KR, Schwade ND, Roland PS. Source: Archives of Otolaryngology--Head & Neck Surgery. 2002 June; 128(6): 660-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049560&dopt=Abstract

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Surgical management of chronic otitis media: beyond tympanotomy tubes. Author(s): Haynes DS, Harley DH. Source: Otolaryngologic Clinics of North America. 2002 August; 35(4): 827-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487084&dopt=Abstract

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Surgical management of otitis media. Author(s): DeRosa J, Grundfast KM. Source: Pediatric Annals. 2002 December; 31(12): 814-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503439&dopt=Abstract

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Surgical management of uncomplicated otitis media in a pediatric Medicaid population. Author(s): Berman S, Bondy J, Byrns PJ, Lezotte D. Source: The Annals of Otology, Rhinology, and Laryngology. 2000 July; 109(7): 623-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903041&dopt=Abstract

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Symptoms of acute otitis media. Author(s): Kontiokari T, Koivunen P, Niemela M, Pokka T, Uhari M. Source: The Pediatric Infectious Disease Journal. 1998 August; 17(8): 676-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9726339&dopt=Abstract

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Systemic steroid for chronic otitis media with effusion in children. Author(s): Mandel EM, Casselbrant ML, Rockette HE, Fireman P, Kurs-Lasky M, Bluestone CD. Source: Pediatrics. 2002 December; 110(6): 1071-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456902&dopt=Abstract

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TEOAE after treatment of otitis media with effusion. Author(s): Niedzielska G, Katska E. Source: Ann Univ Mariae Curie Sklodowska [med]. 2002; 57(2): 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898819&dopt=Abstract

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The effect of otitis media with effusion on perceptual masking. Author(s): Hall JW, Grose JH, Buss E, Dev MB, Drake AF, Pillsbury HC. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 October; 129(10): 105662. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568787&dopt=Abstract

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The entity known as chronic silent (subclinical) otitis media: a common lesion and a forgotten diagnosis. Author(s): Ferlito A, Paparella MM, Rinaldo A, Schachern PA, Cureoglu S. Source: Acta Oto-Laryngologica. 2003 August; 123(6): 749-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953778&dopt=Abstract

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The impact of atopy on neutrophil activity in middle ear effusion from children and adults with chronic otitis media. Author(s): Hurst DS, Venge P. Source: Archives of Otolaryngology--Head & Neck Surgery. 2002 May; 128(5): 561-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003588&dopt=Abstract

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The role of computerized tomography in the preoperative assessment of chronic suppurative otitis media. Author(s): Walshe P, McConn Walsh R, Brennan P, Walsh M. Source: Clinical Otolaryngology and Allied Sciences. 2002 April; 27(2): 95-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994113&dopt=Abstract

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The use of osteopathic manipulative treatment as adjuvant therapy in children with recurrent acute otitis media. Author(s): Mills MV, Henley CE, Barnes LL, Carreiro JE, Degenhardt BF. Source: Archives of Pediatrics & Adolescent Medicine. 2003 September; 157(9): 861-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963590&dopt=Abstract

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Topical treatment of chronic suppurative otitis media in Aboriginal children. Author(s): Coates H. Source: Ear, Nose, & Throat Journal. 2003 August; 82(8 Suppl 2): 13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974052&dopt=Abstract

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Treatment of otitis media with observation and a safety-net antibiotic prescription. Author(s): Siegel RM, Kiely M, Bien JP, Joseph EC, Davis JB, Mendel SG, Pestian JP, DeWitt TG. Source: Pediatrics. 2003 September; 112(3 Pt 1): 527-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949278&dopt=Abstract

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Trends in otitis media among children in the United States. Author(s): Auinger P, Lanphear BP, Kalkwarf HJ, Mansour ME. Source: Pediatrics. 2003 September; 112(3 Pt 1): 514-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949276&dopt=Abstract

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Tumor necrosis factor-alpha and interleukin-1beta levels in recurrent and persistent otitis media with effusion. Author(s): Yetiser S, Satar B, Gumusgun A, Unal F, Ozkaptan Y. Source: Otolaryngology and Head and Neck Surgery. 2002 April; 126(4): 417-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997784&dopt=Abstract

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Uncommon and unusual complications of otitis media with effusion. Author(s): van Cauwenberge P, Watelet JB, Dhooge I. Source: International Journal of Pediatric Otorhinolaryngology. 1999 October 5; 49 Suppl 1: S119-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577789&dopt=Abstract

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Unilateral facial paralysis occurring in an infant with enteroviral otitis media and aseptic meningitis. Author(s): Hostetler MA, Suara RO, Denison MR. Source: The Journal of Emergency Medicine. 2002 April; 22(3): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932090&dopt=Abstract

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Unusual extracranial complications of otitis media in a young HIV patient: retropharyngeal and Mouret's abscess. Author(s): Mevio E, Calabro P, De Paoli F, Maccabruni A, Michelone G. Source: Rev Laryngol Otol Rhinol (Bord). 1998; 119(3): 199-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9770069&dopt=Abstract

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Update on the development and use of viral and bacterial vaccines for the prevention of acute otitis media. Author(s): Greenberg DP. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2001 November-December; 22(6): 353-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775392&dopt=Abstract

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Update on topical ototoxicity in chronic suppurative otitis media. Author(s): Rutka J. Source: Ear, Nose, & Throat Journal. 2002 August; 81(8 Suppl 1): 18-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199183&dopt=Abstract

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Upper respiratory infections--otitis media. Author(s): Warren TB, Warren DP, Soper DE. Source: Infectious Diseases in Obstetrics and Gynecology. 1998; 6(3): 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9785105&dopt=Abstract

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Upper respiratory tract infections - otitis media, sinusitis and pharyngitis. Author(s): Oh HM. Source: Singapore Med J. 1995 August; 36(4): 428-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8919162&dopt=Abstract

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Use of a hyaluronan-based biomembrane in the treatment of chronic cholesteatomatous otitis media. Author(s): Martini A, Morra B, Aimoni C, Radice M. Source: The American Journal of Otology. 2000 July; 21(4): 468-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912689&dopt=Abstract

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Use of adenoidectomy and adenotonsillectomy in children with otitis media with effusion. Author(s): Abdul-Baqi KJ, Shakhatreh FM, Khader QA. Source: Ear, Nose, & Throat Journal. 2001 September; 80(9): 647-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579851&dopt=Abstract

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Using a balancing procedure in multicenter clinical trials. Simulation of patient allocation based on a trial of ventilation tubes for otitis media with effusion in infants. Author(s): Rovers MM, Straatman H, Zielhuis GA, Ingels K, van der Wilt GJ. Source: International Journal of Technology Assessment in Health Care. 2000 Winter; 16(1): 276-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815372&dopt=Abstract

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Vaccination and otitis media. Author(s): Karma P. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 2002 MarchApril; 64(2): 80-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021498&dopt=Abstract

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Vaccination for the prevention of acute otitis media: proof of concept and current challenges. Author(s): Pelton SI. Source: Pediatric Annals. 2002 December; 31(12): 804-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503438&dopt=Abstract

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Vaccine prevention of acute otitis media. Author(s): Greenberg DP, Hoberman A. Source: Curr Allergy Asthma Rep. 2001 July; 1(4): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892059&dopt=Abstract

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Vaccines and otitis media. Author(s): Black S, Shinefield H. Source: Pediatric Annals. 2000 October; 29(10): 648-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056938&dopt=Abstract

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Ventilation time of the middle ear in otitis media with effusion (OME) after CO2 laser myringotomy. Author(s): Sedlmaier B, Jivanjee A, Gutzler R, Huscher D, Jovanovic S. Source: The Laryngoscope. 2002 April; 112(4): 661-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150520&dopt=Abstract

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Ventilation tubes after surgery for otitis media with effusion or acute otitis media and swimming. Systematic review and meta-analysis. Author(s): Carbonell R, Ruiz-Garcia V. Source: International Journal of Pediatric Otorhinolaryngology. 2002 December 2; 66(3): 281-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443818&dopt=Abstract

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Viral and bacterial interaction in acute otitis media. Author(s): Chonmaitree T. Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5 Suppl): S24-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821469&dopt=Abstract

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Viral otitis media. Author(s): Buchman CA, Brinson GM. Source: Curr Allergy Asthma Rep. 2003 July; 3(4): 335-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791211&dopt=Abstract

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Viral RNA in middle ear mucosa and exudates in patients with chronic otitis media with effusion. Author(s): Moyse E, Lyon M, Cordier G, Mornex JF, Collet L, Froehlich P. Source: Archives of Otolaryngology--Head & Neck Surgery. 2000 September; 126(9): 1105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979124&dopt=Abstract

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Viruses and acute otitis media. Author(s): Chonmaitree T, Heikkinen T. Source: The Pediatric Infectious Disease Journal. 2000 October; 19(10): 1005-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055605&dopt=Abstract

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Waldeyer's ring and otitis media: the nasopharyngeal tonsil and otitis media. Author(s): Bernstein JM. Source: International Journal of Pediatric Otorhinolaryngology. 1999 October 5; 49 Suppl 1: S127-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577790&dopt=Abstract

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Watchful waiting in childhood otitis media with effusion. Author(s): Browning GG. Source: Clinical Otolaryngology and Allied Sciences. 2001 August; 26(4): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559333&dopt=Abstract

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Wegener's granulomatosis presenting as a recurrence of chronic otitis media. Author(s): Hartl DM, Aidan P, Brugiere O, Sterkers O. Source: American Journal of Otolaryngology. 1998 January-February; 19(1): 54-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9470953&dopt=Abstract

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What is the natural history of recurrent acute otitis media in infancy? Author(s): Alho OP, Laara E, Oja H. Source: The Journal of Family Practice. 1996 September; 43(3): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8797753&dopt=Abstract

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What is your assessment? Otitis media with effusion. Author(s): Belkengren R, Sapala S. Source: Pediatric Nursing. 1995 May-June; 21(3): 304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7792115&dopt=Abstract

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What role for antibiotics in otitis media and sinusitis? Author(s): Ahuja GS, Thompson J. Source: Postgraduate Medicine. 1998 September; 104(3): 93-9, 103-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9742906&dopt=Abstract

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What to expect from medical treatment of otitis media. Author(s): Rosenfeld RM. Source: The Pediatric Infectious Disease Journal. 1995 September; 14(9): 731-7; Quiz 738. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8559620&dopt=Abstract

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What's new in the diagnosis and management of otitis media? Author(s): Klein JO. Source: Pediatric Annals. 2002 December; 31(12): 777-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503435&dopt=Abstract

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Why are NICU infants at risk for chronic otitis media with effusion? Author(s): Engel J, Mahler E, Anteunis L, Marres E, Zielhuis G. Source: International Journal of Pediatric Otorhinolaryngology. 2001 February; 57(2): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165651&dopt=Abstract

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Xylitol administered only during respiratory infections failed to prevent acute otitis media. Author(s): Tapiainen T, Luotonen L, Kontiokari T, Renko M, Uhari M. Source: Pediatrics. 2002 February; 109(2): E19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11826229&dopt=Abstract

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Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial. Author(s): Uhari M, Kontiokari T, Koskela M, Niemela M. Source: Bmj (Clinical Research Ed.). 1996 November 9; 313(7066): 1180-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916749&dopt=Abstract

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Xylitol for prevention of acute otitis media. Author(s): Lagace E. Source: The Journal of Family Practice. 1999 February; 48(2): 89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10037531&dopt=Abstract

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Xylitol in preventing acute otitis media. Author(s): Uhari M, Tapiainen T, Kontiokari T. Source: Vaccine. 2000 December 8; 19 Suppl 1: S144-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11163479&dopt=Abstract

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Xylitol prophylaxis for acute otitis media: tout de suite? Author(s): Mitchell AA. Source: Pediatrics. 1998 October; 102(4 Pt 1): 974-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9786773&dopt=Abstract

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CHAPTER 2. NUTRITION AND OTITIS MEDIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and otitis media.

Finding Nutrition Studies on Otitis Media 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 “otitis media” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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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 is a typical result when searching for recently indexed consumer information on otitis media: •

Breast feeding prevents otitis media. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. August 1983. volume 41 (8) page 241-242. 0029-6643

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Breast-feeding protect against otitis media. Source: Sheard, N.F. Nutrition-reviews (USA). (September 1993). volume 51(9) page 275277. breast feeding otitis infants 0029-6643

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

A cost-utility analysis of second-line antibiotics in the treatment of acute otitis media in children. Author(s): Division of Clinical Pharmacology, University of Toronto, Ontario, Canada. Source: Oh, P I Maerov, P Pritchard, D Knowles, S R Einarson, T R Shear, N H ClinTher. 1996 Jan-February; 18(1): 160-82 0149-2918

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Acute otitis media and sociomedical risk factors among unselected children in Greenland. Author(s): Department of Otolaryngology, Head & Neck Surgery, Rigshospitalet, University of Copenhagen, Denmark. [email protected] Source: Homoe, P Christensen, R B Bretlau, P Int-J-Pediatr-Otorhinolaryngol. 1999 June 15; 49(1): 37-52 0165-5876

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Altered immunoregulation in otitis media with effusion in children: presence of serum immuno-inhibitory factors. Author(s): Otorhinolaryngology Clinic, University Clinical Center, Belgrade, Serbia. Source: Djeric, D R Ramic, Z D Mostarica, M B Stojkovic, M B Stepanovic, S R Lukic, M L Clin-Otolaryngol. 1994 June; 19(3): 234-6 0307-7772

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Amusing parents while nature cures otitis media with effusion. Author(s): State University of New York Health Science at Brooklyn, USA. [email protected] Source: Rosenfeld, R M Int-J-Pediatr-Otorhinolaryngol. 1998 March 1; 43(2): 189-92 01655876

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Arachidonic acid metabolites in otitis media pathogenesis. Author(s): Division of Otolaryngology-Head & Neck Surgery, Loma Linda University School of Medicine, California. Source: Jung, T T Ann-Otol-Rhinol-Laryngol-Suppl. 1988 May-Jun; 13214-8 0096-8056

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Causes for massive bacterial colonization on mucosal membranes during infectious mononucleosis: implications for acute otitis media. Author(s): Department of Otolaryngology, Institute of Clinical Medicine, University of Tromso, N-9037, Tromso, Norway. [email protected] Source: Stenfors, L E Bye, H M Raisanen, S Int-J-Pediatr-Otorhinolaryngol. 2002 September 24; 65(3): 233-40 0165-5876

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Challenges of evaluating homeopathic treatment of acute otitis media. Author(s): Maxwell Finland Laboratory for Infectious Diseases and Department of Pediatrics, Boston Medical Center, MA 02118, USA. [email protected] Source: Barnett, E D Levatin, J L Chapman, E H Floyd, L A Eisenberg, D Kaptchuk, T J Klein, J O Pediatr-Infect-Dis-J. 2000 April; 19(4): 273-5 0891-3668

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Changes in goblet cell density in rat middle ear mucosa in acute otitis media. Author(s): Department of Otorhinolaryngology, Gentofte University Hospital of Copenhagen, Denmark. Source: Caye Thomasen, P Hermansson, A Tos, M Prellner, K Am-J-Otol. 1995 January; 16(1): 75-82 0192-9763

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Chronic suppurative otitis media in indigenous populations: the Australian aborigine. Author(s): Princess Margaret Hospital for Children, Perth, Western Australia. Source: Coates, H Ear-Nose-Throat-J. 2002 August; 81(8 Suppl 1): 11-2 0145-5613

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Clinical efficacy of an antiallergic drug on otitis media with effusion in association with allergic rhinitis. Author(s): Department of Otolaryngology, Oita Medical University, Japan. Source: Suzuki, M Kawauchi, H Mogi, G Auris-Nasus-Larynx. 1999 April; 26(2): 123-9 0385-8146

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Clinical evaluation of S-CMC syrup applied in the treatment of otitis media with effusion. Double blind comparative test with placebo. Author(s): Department of Otolaryngology, Kansai Medical University, Osaka. Source: Kumazawa, T Ushiro, K Acta-Otolaryngol-Suppl. 1988; 45856-62 0365-5237

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Effect of lacto-N-neotetraose, asialoganglioside-GM1 and neuraminidase on adherence of otitis media-associated serotypes of Streptococcus pneumoniae to chinchilla tracheal epithelium. Author(s): Department of Otolaryngology, The Ohio State University, Columbus, Ohio 43210-1282, USA. Source: Tong, H H McIver, M A Fisher, L M DeMaria, T F Microb-Pathog. 1999 February; 26(2): 111-9 0882-4010

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Effect of N-acetylcysteine on the incidence of recurrence of otitis media with effusion and re-insertion of ventilation tubes. Author(s): ENT Department, Aarhus University Hospital, Denmark. Source: Ovesen, T Felding, J U Tommerup, B Schousboe, L P Petersen, C G ActaOtolaryngol-Suppl. 2000; 54379-81 0365-5237

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Effect of prostaglandin, leukotriene, and arachidonic acid on experimental otitis media with effusion in chinchillas. Author(s): Department of Surgery, Loma Linda University School of Medicine, California. Source: Jung, T T Park, Y M Schlund, D Weeks, D Miller, S Wong, O Juhn, S K Ann-OtolRhinol-Laryngol-Suppl. 1990 Jun; 14828-32 0096-8056

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Effects of 21-aminosteroid U-74389G on acute otitis media in a guinea pig model. Author(s): Columbia University, New York, New York, USA. Source: Haddad, J Egusa, K Takoudes, T G Otolaryngol-Head-Neck-Surg. 1998 January; 118(1): 44-8 0194-5998

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Effects of Allergina on the treatment of otitis media with effusions. Author(s): Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Chonbuk, Republic of Korea. Source: Jeong, H J Hong, S H Kim, S C Park, E J Jang, C H Kim, K S Kim, H M Inflammation. 2002 April; 26(2): 89-95 0360-3997

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Effects of myringotomy and orally administered drugs on viscosity and elasticity of middle ear effusions from children with otitis media with effusion. Author(s): Department of Otorhinolaryngology, Mie University School of Medicine, Japan. Source: Majima, Y Takeuchi, K Sakakura, Y Acta-Otolaryngol-Suppl. 1990; 47166-72 0365-5237

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Effects of sulphur dioxide and smoke on the incidence of secretory otitis media. Author(s): Ear, Nose and Throat Department, Zagreb University School of Medicine, Croatia. Source: Sprem, N Branica, S Arh-Hig-Rada-Toksikol. 1993 September; 44(3): 229-32 00041254

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Epidemiology of otitis media onset by six months of age. Author(s): Otitis Media Research Center, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA. Source: Daly, K A Brown, J E Lindgren, B R Meland, M H Le, C T Giebink, G S Pediatrics. 1999 June; 103(6 Pt 1): 1158-66 0031-4005

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Experimental otitis media with effusion induced by leukotriene D4. Author(s): Department of Otorhinolaryngology, Kansai Medical University, 10-15 Fumizono, 570-8506, Moriguchi, Japan. [email protected] Source: Tada, N Furukawa, M Ogura, M Arai, S Adachi, Y Ikehara, S Yamashita, T Auris-Nasus-Larynx. 2002 April; 29(2): 127-32 0385-8146

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Expression of acute otitis media after receptor blockade of platelet activating factor, thromboxane, and leukotrienes in the chinchilla. Author(s): Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA. Source: Diven, W F Burckart, G J Alper, C M Jaffe, R Evans, R W Doyle, W J Ann-OtolRhinol-Laryngol. 1998 March; 107(3): 199-206 0003-4894

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Home medication and microbiological profile in chronic otitis media in some Nigerian children. Author(s): Department of Medical Microbiology & Parasitology, University of Calabar Teaching Hospital, Nigeria. Source: Utsalo, S J Onoyom Ita, V Ifeanyi Chukwu, M Akpan, J O Cent-Afr-J-Med. 1990 November; 36(11): 278-83 0008-9176

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Homeopathy in acute otitis media in children: treatment effect or spontaneous resolution? Author(s): Spezialarzt FMH fur Kinder and Jugendliche, FA Homoopathie SVHA, Laupen, Switzerland. [email protected] Source: Frei, H Thurneysen, A Br-Homeopath-J. 2001 October; 90(4): 180-2 0007-0785

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Inflammatory mediators and otitis media with effusion. An experimental approach using cell culture. Author(s): Laboratoire d'Otologie Experimentale, Faculte Lariboisiere-St-Louis, Paris, France. Source: Tan, C T Herman, P Auris-Nasus-Larynx. 1998 January; 25(1): 25-32 0385-8146

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Lemon-flavored cod liver oil and a multivitamin-mineral supplement for the secondary prevention of otitis media in young children: pilot research. Author(s): Department of Otolaryngology, The New York Eye and Ear Infirmary, and The College of Physicians and Surgeons, Columbia University, New York, USA. [email protected]

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Source: Linday, Linda A Dolitsky, Jay N Shindledecker, Richard D Pippenger, C E AnnOtol-Rhinol-Laryngol. 2002 July; 111(7 Pt 1): 642-52 0003-4894 •

Local application of N-acetylcysteine in secretory otitis media in rabbits. Author(s): Ear, Nose and Throat Department, Aarhus University Hospital, Denmark. Source: Ovesen, T Paaske, P B Elbroend, O Clin-Otolaryngol. 1992 August; 17(4): 327-31 0307-7772

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Management of acute otitis media in an era of increasing antibiotic resistance. Author(s): Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, MA 02118, USA. [email protected] Source: Klein, J O Int-J-Pediatr-Otorhinolaryngol. 1999 October 5; 49 Suppl 1S15-7 01655876

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Management of otitis media with antimicrobial agents. Author(s): Boston University School of Medicine, Department of Pediatrics, Boston Medical Center, Massachusetts, USA. Source: Klein, J O Curr-Clin-Top-Infect-Dis. 2000; 20174-88 0195-3842

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Medical treatment of chronic otitis media: steroid or antibiotic with steroid ear-drops? Author(s): Department of Otolaryngology, Stobhill General Hospital, Glasgow, U.K. Source: Crowther, J A Simpson, D Clin-Otolaryngol. 1991 April; 16(2): 142-4 0307-7772

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Meningitis in a girl with recurrent otitis media caused by Streptococcus pyogenes-otitis media has to be treated appropriately. Author(s): Children's Hospital, University of Leipzig, Germany. [email protected] Source: Steppberger, K Adams, I Deutscher, J Muller, H Kiess, W Infection. 2001 October; 29(5): 286-8 0300-8126

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Moraxella (Branhamella) catarrhalis-induced experimental otitis media in the chinchilla. Author(s): Department of Otolaryngology, Ohio State University College of Medicine, Columbus. Source: Chung, M H Enrique, R Lim, D J De Maria, T F Acta-Otolaryngol. 1994 July; 114(4): 415-22 0001-6489

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New developments in treating otitis media. Author(s): Otitis Media Research Center, University of Minnesota School of Medicine, Minneapolis. Source: Paparella, M M Schachern, P Ann-Otol-Rhinol-Laryngol-Suppl. 1994 May; 163710 0096-8056

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Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children. Author(s): Department of General Practice, University of Wales College of Medicine, Llanedeyrn Health Centre, Llanedeyrn, Cardiff, South Galmorgan, UK, CF3 7PN. [email protected] Source: Butler, C C van Der Voort JH Cochrane-Database-Syst-Revolume 2000; (4): CD001935 1469-493X

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Otitis media in Greenland. Studies on historical, epidemiological, microbiological, and immunological aspects. Source: Homoe, P Int-J-Circumpolar-Health. 2001; 60 Suppl 2: 1-54 1239-9736

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Otitis media with effusion. Author(s): Southampton University, Southampton, UK. Source: Williamson, I Clin-Evid. 2002 June; (7): 469-76 1462-3846

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Otitis media: current treatment issues & trends. Source: McAdams, C C Heller, C Calandra, L M Adv-Nurse-Pract. 2001 February; 9(2): 69-70, 73-4 1096-6293

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Participation of Ras and extracellular regulated kinase in the hyperplastic response of middle-ear mucosa during bacterial otitis media. Author(s): Department of Head and Neck Surgery, University of California, San Diego, School of Medicine, La Jolla, California, USA. Source: Palacios, S D Pak, K Kayali, A G Rivkin, A Z Aletsee, C Melhus, A Webster, N J Ryan, A F J-Infect-Dis. 2002 December 15; 186(12): 1761-9 0022-1899

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Prostaglandins, leukotrienes, and other arachidonic acid metabolites in the pathogenesis of otitis media. Author(s): Department of Surgery, Loma Linda University School of Medicine, CA. Source: Jung, T T Laryngoscope. 1988 September; 98(9): 980-93 0023-852X

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The herbal medicine, sairei-to, prevents endotoxin-induced otitis media with effusion in the guinea pig. Author(s): Department of Otolaryngology, Osaka City University Medical School, Japan. Source: Sugiura, Y Ohashi, Y Nakai, Y Acta-Otolaryngol-Suppl. 1997; 53121-33 0365-5237

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The light at the end of the tunnel associated with the high prevalence of chronic otitis media among Inuit elementary school children in the Eastern Canadian Arctic is now visible. Author(s): McGill Baffin Program, McGill University, Montreal, Quebec. Source: Baxter, J D Stubbing, P Goodbody, L Terraza, O Arctic-Med-Res. 1992 January; 51(1): 29-31 0782-226X

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The management of chronic suppurative otitis media with acid media solution. Author(s): Kuwaiti Hospital, Dubai, United Arab Emirates. Source: Aminifarshidmehr, N Am-J-Otol. 1996 January; 17(1): 24-5 0192-9763

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The role of Mucodyne in reducing the need for surgery in patients with persistent otitis media with effusion. Author(s): Departments of Otolaryngology/Head and Neck Surgery, Pain Relief and Paediatrics, Oxford Radcliffe Hospitals (Radcliffe Infirmary, Churchill Hospital and John Radcliffe Hospital) Oxford, UK. Source: Commins, D J Koay, B C Bates, G J Moore, R A Sleeman, K Mitchell, B Bates, S Clin-Otolaryngol. 2000 August; 25(4): 274-9 0307-7772

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Topical and systemic treatment for chronic suppurative otitis media. Author(s): Department of Otolaryngology, Klinikum Dortmund Teaching Hospital, Dortmund, Germany. Source: Deitmer, T Ear-Nose-Throat-J. 2002 August; 81(8 Suppl 1): 16-7 0145-5613

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Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi. Author(s): Ear Clinic, Bamalete Lutheran Hospital, Ramotswa, Botswana. [email protected] Source: van Hasselt, Piet van Kregten, Eric Int-J-Pediatr-Otorhinolaryngol. 2002 March 15; 63(1): 49-56 0165-5876

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Treatment of secretory otitis media with kampo medicine. Author(s): Department of Otolaryngology, Tohoku University School of Medicine, Sendai, Japan. Source: Ikeda, K Takasaka, T Arch-Otorhinolaryngol. 1988; 245(4): 234-6 0302-9530

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Tuberculous otitis media -- a diagnostic dilemma. Author(s): Department of Otolaryngology, University Hospital Aintree, Lower Lane, Liverpool L9 7AL, UK. Source: Bhalla, R K Jones, T M Rothburn, M M Swift, A C Auris-Nasus-Larynx. 2001 August; 28(3): 241-3 0385-8146

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Turicella otitidis gen. nov., sp. nov., a coryneform bacterium isolated from patients with otitis media. Author(s): Institute of Medical Microbiology, University of Zurich, Switzerland. Source: Funke, G Stubbs, S Altwegg, M Carlotti, A Collins, M D Int-J-Syst-Bacteriol. 1994 April; 44(2): 270-3 0020-7713

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

A feasibility study of chiropractic spinal manipulation versus sham spinal manipulation for chronic otitis media with effusion in children. Author(s): Sawyer CE, Evans RL, Boline PD, Branson R, Spicer A. Source: Journal of Manipulative and Physiological Therapeutics. 1999 June; 22(5): 292-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10395431&dopt=Abstract

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Acoustic otoscopy in the diagnosis of otitis media. Author(s): Jehle D, Cottington E. Source: Annals of Emergency Medicine. 1989 April; 18(4): 396-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2650590&dopt=Abstract

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Acupuncture treatment for aerotitis media. Author(s): Tian ZM.

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Source: J Tradit Chin Med. 1985 December; 5(4): 259-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3834237&dopt=Abstract •

Amusing parents while nature cures otitis media with effusion. Author(s): Rosenfeld RM. Source: International Journal of Pediatric Otorhinolaryngology. 1998 March 1; 43(2): 18992. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578129&dopt=Abstract

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An integrated osteopathic treatment approach in acute otitis media. Author(s): Pintal WJ, Kurtz ME. Source: J Am Osteopath Assoc. 1989 September; 89(9): 1139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2793535&dopt=Abstract

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Auditory brain stem responses in rhesus monkey with otitis media with effusion. Author(s): Fria TJ, Saad MM, Doyle WJ, Cantekin EI. Source: Otolaryngology and Head and Neck Surgery. 1982 November-December; 90(6): 824-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994437&dopt=Abstract

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Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media. Author(s): Dagan R, Hoberman A, Johnson C, Leibovitz EL, Arguedas A, Rose FV, Wynne BR, Jacobs MR. Source: The Pediatric Infectious Disease Journal. 2001 September; 20(9): 829-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734759&dopt=Abstract

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Binaural masking level differences in infants with and without otitis media with effusion. Author(s): Hutchings ME, Meyer SE, Moore DR. Source: Hearing Research. 1992 November; 63(1-2): 71-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1464577&dopt=Abstract

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Cefprozil versus high-dose amoxicillin/clavulanate in children with acute otitis media. Author(s): Hedrick JA, Sher LD, Schwartz RH, Pierce P. Source: Clinical Therapeutics. 2001 February; 23(2): 193-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293553&dopt=Abstract

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Challenges of evaluating homeopathic treatment of acute otitis media. Author(s): Barnett ED, Levatin JL, Chapman EH, Floyd LA, Eisenberg D, Kaptchuk TJ, Klein JO.

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Source: The Pediatric Infectious Disease Journal. 2000 April; 19(4): 273-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783013&dopt=Abstract •

Changes in external ear resonance after ventilation tube (Grommet) insertion in children with otitis media with effusion. Author(s): Hong SH, Cho YS, Chung WH, Koh SJ, Seo IS, Woo HC. Source: International Journal of Pediatric Otorhinolaryngology. 2001 April 27; 58(2): 14752. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11278023&dopt=Abstract

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Chronic suppurative otitis media in indigenous populations: the Australian aborigine. Author(s): Coates H. Source: Ear, Nose, & Throat Journal. 2002 August; 81(8 Suppl 1): 11-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199180&dopt=Abstract

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Comparison of tone burst and tapping evocation of myogenic potentials in patients with chronic otitis media. Author(s): Yang TL, Young YH. Source: Ear and Hearing. 2003 June; 24(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799539&dopt=Abstract

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Effects of Allergina on the treatment of otitis media with effusions. Author(s): Jeong HJ, Hong SH, Kim SC, Park EJ, Jang CH, Kim KS, Kim HM. Source: Inflammation. 2002 April; 26(2): 89-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989792&dopt=Abstract

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Effects of myringotomy and orally administered drugs on viscosity and elasticity of middle ear effusions from children with otitis media with effusion. Author(s): Majima Y, Takeuchi K, Sakakura Y. Source: Acta Otolaryngol Suppl. 1990; 471: 66-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2239251&dopt=Abstract

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Efficacy of naturopathic extracts in the management of ear pain associated with acute otitis media. Author(s): Sarrell EM, Mandelberg A, Cohen HA. Source: Archives of Pediatrics & Adolescent Medicine. 2001 July; 155(7): 796-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434846&dopt=Abstract

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ELISA to determine immunoreactive Pseudomonas aeruginosa elastase in chronic suppurative otitis media. Author(s): Jin CS, Hamaguchi Y, Sakakura Y.

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Source: Int Arch Allergy Appl Immunol. 1991; 96(3): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1804790&dopt=Abstract •

Evidence in infants with cleft palate that breast milk protects against otitis media. Author(s): Paradise JL, Elster BA, Tan L. Source: Pediatrics. 1994 December; 94(6 Pt 1): 853-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7971001&dopt=Abstract

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Forcefeeding practices and otitis media in Ilorin, Nigeria. Author(s): Adedoyin MA. Source: East Afr Med J. 1989 January; 66(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2917496&dopt=Abstract

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Galbreath technique: a manipulative treatment for otitis media revisited. Author(s): Pratt-Harrington D. Source: J Am Osteopath Assoc. 2000 October; 100(10): 635-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105452&dopt=Abstract

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Home medication and microbiological profile in chronic otitis media in some Nigerian children. Author(s): Utsalo SJ, Onoyom-Ita V, Ifeanyi-Chukwu M, Akpan JO. Source: Cent Afr J Med. 1990 November; 36(11): 278-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2092881&dopt=Abstract

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Homeopathic treatment of acute otitis media in children: a preliminary randomized placebo-controlled trial. Author(s): Jacobs J, Springer DA, Crothers D. Source: The Pediatric Infectious Disease Journal. 2001 February; 20(2): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11224838&dopt=Abstract

•

Homeopathy in acute otitis media in children: treatment effect or spontaneous resolution? Author(s): Frei H, Thurneysen A. Source: Br Homeopath J. 2001 October; 90(4): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680801&dopt=Abstract

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Impedance audiometry in serous otitis media. Author(s): Orchik DJ, Morff R, Dunn JW. Source: Arch Otolaryngol. 1978 July; 104(7): 409-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=666650&dopt=Abstract

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Influence of otitis media on hearing and development. Author(s): Dobie RA, Berlin CI. Source: Ann Otol Rhinol Laryngol Suppl. 1979 September-October; 88(5 Pt 2 Suppl 60): 48-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=115362&dopt=Abstract

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Laterally hypertrophic adenoids as a contributing factor in otitis media. Author(s): Wright ED, Pearl AJ, Manoukian JJ. Source: International Journal of Pediatric Otorhinolaryngology. 1998 October 15; 45(3): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9865437&dopt=Abstract

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Lemon-flavored cod liver oil and a multivitamin-mineral supplement for the secondary prevention of otitis media in young children: pilot research. Author(s): Linday LA, Dolitsky JN, Shindledecker RD, Pippenger CE. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 July; 111(7 Pt 1): 64252. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126022&dopt=Abstract

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Management of acute otitis media in an era of increasing antibiotic resistance. Author(s): Klein JO. Source: International Journal of Pediatric Otorhinolaryngology. 1999 October 5; 49 Suppl 1: S15-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577768&dopt=Abstract

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Management of deafness in otitis media with effusion. Author(s): Mauer TP. Source: J Am Osteopath Assoc. 1966 December; 66(4): 421-30. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5341407&dopt=Abstract

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Management of otitis media using Agency for Health Care Policy and Research guidelines.The Agency for Health Care Policy and Research. Author(s): Hsu GS, Levine SC, Giebink GS. Source: Otolaryngology and Head and Neck Surgery. 1998 April; 118(4): 437-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9560092&dopt=Abstract

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Management of otitis media with antimicrobial agents. Author(s): Klein JO. Source: Curr Clin Top Infect Dis. 2000; 20: 174-88. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943524&dopt=Abstract

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Management of otitis media: 2000 and beyond. Author(s): Klein JO. Source: The Pediatric Infectious Disease Journal. 2000 April; 19(4): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783040&dopt=Abstract

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Modern management of acute otitis media. Author(s): Weber SM, Grundfast KM. Source: Pediatric Clinics of North America. 2003 April; 50(2): 399-411. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809330&dopt=Abstract

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Naturopathic ear drops minimally effective for acute otitis media. Author(s): Fay DL, Schellhase KG, Wujek D. Source: The Journal of Family Practice. 2003 September; 52(9): 673, 676. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967533&dopt=Abstract

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Osteopathic manipulation to prevent otitis media--does it work? Author(s): Pichichero ME. Source: Archives of Pediatrics & Adolescent Medicine. 2003 September; 157(9): 852-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963587&dopt=Abstract

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Otitis media in Greenland. Studies on historical, epidemiological, microbiological, and immunological aspects. Author(s): Homoe P. Source: Int J Circumpolar Health. 2001; 60 Suppl 2: 1-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725622&dopt=Abstract

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Otitis media, milk allergy, and folk medicine. Author(s): Phillips BL, Bland RD. Source: Pediatrics. 1972 August; 50(2): 346. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5068100&dopt=Abstract

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Otitis media: current treatment issues & trends. Author(s): McAdams CC, Heller C, Calandra LM. Source: Adv Nurse Pract. 2001 February; 9(2): 69-70, 73-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416058&dopt=Abstract

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Otoacoustic emissions and tympanometry in children with otitis media. Author(s): Koivunen P, Uhari M, Laitakari K, Alho OP, Luotonen J. Source: Ear and Hearing. 2000 June; 21(3): 212-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890729&dopt=Abstract

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Pseudomonas otitis media and bacteremia following a water birth. Author(s): Parker PC, Boles RG. Source: Pediatrics. 1997 April; 99(4): 653. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9093328&dopt=Abstract

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Reflectometric screening for otitis media: inconsistencies in a sample of Australian aboriginal children. Author(s): Boswell JB, Nienhuys TG. Source: International Journal of Pediatric Otorhinolaryngology. 1993 January; 25(1-3): 49-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8436480&dopt=Abstract

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Shape and displacement patterns of the gerbil tympanic membrane in experimental otitis media with effusion. Author(s): von Unge M, Decraemer WF, Dirckx JJ, Bagger-Sjoback D. Source: Hearing Research. 1995 February; 82(2): 184-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7775284&dopt=Abstract

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Speech perception in children with histories of recurrent otitis media. Author(s): Clarkson RL, Eimas PD, Marean GC. Source: The Journal of the Acoustical Society of America. 1989 February; 85(2): 926-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2926008&dopt=Abstract

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TEOAE after treatment of otitis media with effusion. Author(s): Niedzielska G, Katska E. Source: Ann Univ Mariae Curie Sklodowska [med]. 2002; 57(2): 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898819&dopt=Abstract

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The effects of chronic otitis media with effusion on the measurement of transiently evoked otoacoustic emissions. Author(s): Amedee RG. Source: The Laryngoscope. 1995 June; 105(6): 589-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7769941&dopt=Abstract

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The effects of early bilateral otitis media with effusion on educational attainment: a prospective cohort study. Author(s): Peters SA, Grievink EH, van Bon WH, Schilder AG. Source: Journal of Learning Disabilities. 1994 February; 27(2): 111-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8195687&dopt=Abstract

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The herbal medicine, sairei-to, prevents endotoxin-induced otitis media with effusion in the guinea pig. Author(s): Sugiura Y, Ohashi Y, Nakai Y.

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Source: Acta Otolaryngol Suppl. 1997; 531: 21-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9349884&dopt=Abstract •

The homoeopathic treatment of otitis media in children--comparisons with conventional therapy. Author(s): Friese KH, Kruse S, Ludtke R, Moeller H. Source: Int J Clin Pharmacol Ther. 1997 July; 35(7): 296-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9247843&dopt=Abstract

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The Nakasuk Project- the conservative treatment of chronic otitis media in Inuit elementary school children. Author(s): Baxter JD, Katsarkas A, Ling D, Carson R. Source: The Journal of Otolaryngology. 1979 June; 8(3): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=458916&dopt=Abstract

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The use of osteopathic manipulative treatment as adjuvant therapy in children with recurrent acute otitis media. Author(s): Mills MV, Henley CE, Barnes LL, Carreiro JE, Degenhardt BF. Source: Archives of Pediatrics & Adolescent Medicine. 2003 September; 157(9): 861-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963590&dopt=Abstract

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Treatment of secretory otitis media with kampo medicine. Author(s): Ikeda K, Takasaka T. Source: Arch Otorhinolaryngol. 1988; 245(4): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3052389&dopt=Abstract

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

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

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

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

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drkoop.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 otitis media; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Cellulitis Source: Integrative Medicine Communications; www.drkoop.com Diarrhea Source: Integrative Medicine Communications; www.drkoop.com Ear Infection Source: Integrative Medicine Communications; www.drkoop.com Fever Source: Integrative Medicine Communications; www.drkoop.com Hearing Difficulty Source: Integrative Medicine Communications; www.drkoop.com Infection Source: Healthnotes, Inc.; www.healthnotes.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Otitis Media Source: Integrative Medicine Communications; www.drkoop.com Recurrent Ear Infections Source: Healthnotes, Inc.; www.healthnotes.com Skin Infection Source: Integrative Medicine Communications; www.drkoop.com Vomiting Source: Integrative Medicine Communications; www.drkoop.com

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Alternative Therapy Chiropractic Source: Integrative Medicine Communications; www.drkoop.com Homeopathy Source: Integrative Medicine Communications; www.drkoop.com

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Chinese Medicine Baifan Alternative names: Alum; Baifan (Bai Fan); Alume Source: Chinese Materia Medica

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

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

A Case-control Study of Chronic Otitis Media and Acculturation among the YukonKuskokwim Delta Eskimos (Otitis Media) by Zurita, R. Beatriz, PhD from The University of Michigan, 1992, 191 pages http://wwwlib.umi.com/dissertations/fullcit/9227037

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Acute Otitis Media, Antimicrobial Resistant Streptococcus Pneumoniae, and Prescribing Practices of Nurse Practitioners, Physicians, and Physician Assistants in Alaska by Ervin, Richard Carl; Ms from University of Alaska Anchorage, 2002, 111 pages http://wwwlib.umi.com/dissertations/fullcit/1409965

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An Exploratory Study of the Relationship between Auditory-perceptual Skills and Academic Achievement in an Elementary School Sample of Children with History of Ear Infection (Otitis Media) by Sebenius, Carrie Hoerger; PhD from The Claremont Graduate University, 2000, 154 pages http://wwwlib.umi.com/dissertations/fullcit/9963036

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An Investigation of the Effects of Otitis Media on Academic Aptitude, Social Status and Selected Variables in Elementary School-Age Children by Stagliano, Michael Anthony, PhD from University of Illinois at Urbana-Champaign, 1983, 153 pages http://wwwlib.umi.com/dissertations/fullcit/8310012

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Curriculum Planning for Communicatively Disordered Preschoolers with Recurrent Serous Otitis Media by Newman, Susan Hunt, Edd from State University of New York at Buffalo, 1984, 488 pages http://wwwlib.umi.com/dissertations/fullcit/8417925

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Educational Implications of Recurrent Otitis Media among Children at Risk for Learning Disabilities by Loose, Frances Fein, PhD from Michigan State University, 1984, 158 pages http://wwwlib.umi.com/dissertations/fullcit/8415236

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Knowledge of Five Types of Educational Professionals Regarding Otitis Media and Related Behaviors (Auditory Disorders, Attention Deficit Disorder, Hearing Impaired Children, Native Americans) by Reinholtz, Marcia J., EDD from Northern Arizona University, 1986, 131 pages http://wwwlib.umi.com/dissertations/fullcit/8705750

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Otitis Media among Puerto Ricans and Blacks: Ethnicity, Epidemiology, and Family Health Cultures by Allen, Lisa Winokur, PhD from The University of Connecticut, 1988, 322 pages http://wwwlib.umi.com/dissertations/fullcit/8822907

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Otitis Media with Effusion and Auditory Verbal Short-term Memory by Rasener, Dorothy M.; PhD from Fielding Graduate Institute, 2002, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3064043

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Otitis Media: Its Relationship with Delayed Reading and Attention Deficit Disorder by Kindig, Joan Schroeder, EDD from University of Virginia, 1995, 150 pages http://wwwlib.umi.com/dissertations/fullcit/9600394

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The Effects of Otitis Media, Socioeconomic Status and Other Risk Factors on the Wechsler Preschool and Primary Scale of Intelligence-revised in a Special Education Population (At Risk) by Lutz, Julie Davis, PhD from Hofstra University, 1992, 135 pages http://wwwlib.umi.com/dissertations/fullcit/9224960

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The Influence of Experience on the Perception of Voicing Contrasts As Assessed in Children with Histories of Recurrent Otitis Media by Clarkson, Richard Lewis, PhD from Brown University, 1984, 209 pages http://wwwlib.umi.com/dissertations/fullcit/8422404

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The Presence of Congenital Middle Ear Anomalies and Otitis Media in the Down's Syndrome Population. by Krajicek, Marilyn Jean, Edd from University of Northern Colorado, 1977, 109 pages http://wwwlib.umi.com/dissertations/fullcit/7805503

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The Relationship between Otitis Media and Auditory Memory in Children (Learning Disabilities) by Palefsky, Elliot H., EDD from University of South Carolina, 1986, 90 pages http://wwwlib.umi.com/dissertations/fullcit/8615924

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The Relationship between Persistent Otitis Media with Effusion and Socioeconomic Status to Teacher's Ratings of Social Skills and Behavior in Preschool Children (Hyperactivity) by Taxman Goldfarb, Lisa, PhD from Hofstra University, 1992, 120 pages http://wwwlib.umi.com/dissertations/fullcit/9226041

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Tympanometry in Diagnosis and Follow-Up of Otitis Media in Children Less Than Two Years of Age by Palmu, Arto Antti Ilmari; MD from Tampereen Yliopisto (Finland), 2002, 146 pages http://wwwlib.umi.com/dissertations/fullcit/f794929

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

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CHAPTER 5. CLINICAL TRIALS AND OTITIS MEDIA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning otitis media.

Recent Trials on Otitis Media The following is a list of recent trials dedicated to otitis media.8 Further information on a trial is available at the Web site indicated. •

A Randomized Controlled Trial of the Use of Craniosacral Osteopathic Manipulative Treatment and of Botanical Treatment in Recurrent otitis media in Children. Condition(s): Otitis Media Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: A randomized, blinded, controlled trial will be performed to determine the efficacy of herbal therapy and craniosacral manipulation for the prevention of acute otitis media in children with recurrent otitis media. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010465

•

Adenoidectomy for Otitis media in 2-3 Year Old Children Condition(s): Otitis Media with Effusion Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Deafness and Other Communication Disorders (NIDCD)

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: The purpose of this study is to evaluate the efficacy of three different surgical treatments (1. Bilateral myringotomy and tube insertion (M&T); 2. Adenoidectomy and bilateral myringotomy (A&T); 3. Adenoidectomy with myringotomy and tympanostomy tube insertion (A-M&T)) in reducing subsequent episodes of middle ear disease and hearing loss caused by the fluid in the middle ear in children aged 24-47 months. The fluid in the middle ear is of at least three months' duration and unresponsive to standardized, recent antimicrobial treatment. The children are assigned to one of the three surgical treatments. After surgery, they are followed with examinations monthly and at the time of intercurrent infections for three years. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016497 •

Levofloxacin In The Treatment Of Children With Recurrent And/or Persistent Acute Otitis Media Condition(s): Otitis Media Study Status: This study is currently recruiting patients. Sponsor(s): Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Purpose - Excerpt: The purpose of this study is to demonstrate non-inferiority of levofloxacin compared with amoxicillin/clavulanate on the clinical response at the end of therapy in infants and children who have recurrent and/or persistent acute otitis media. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051753

•

Acute Otitis Media: Adjuvant Therapy to Improve Outcome Condition(s): Otitis Media Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute on Deafness and Other Communication Disorders (NIDCD) Purpose - Excerpt: Acute otitis media is one of the most common diseases of childhood and is one of the major causes of hearing loss in children. Despite the availability of effective antibiotic therapy for otitis media, treatment failures, persistent effusions, and recurrences are common. This Phase III outpatient study aims to test whether adjuvant therapy (an antihistamine or a corticosteroid), in addition to antibiotic therapy, improves the acute and long-term outcomes of patients with acute otitis media. This study is targeted to recruiting 200 infants (age less than one year); patient (and parent) participation is estimated to continue for one year after enrollment. Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000363 •

Study of Levofloxacin to Evaluate Bacteriologic Outcome In Children with Difficult To Treat Acute Otitis Media Condition(s): Otitis Media Study Status: This study is completed. Sponsor(s): Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Purpose - Excerpt: The purpose of the study is to assess the rate of eradication of bacteria from the middle ear fluid 4 to 6 days after the initiation of treatment with levofloxacin in infants and children who have acute otitis media and are at high risk for infections that are difficult to treat. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044473

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 6. PATENTS ON OTITIS MEDIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “otitis media” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on otitis media, we have not necessarily excluded non-medical patents in this bibliography.

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

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

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example of the type of information that you can expect to obtain from a patent search on otitis media: •

Artificial middle ear and ear canal prosthesis Inventor(s): Grote; Johannes J. (Bolwerkshof, Lerop, St. Odilienberg, NL) Assignee(s): none reported Patent Number: 4,169,292 Date filed: November 14, 1977 Abstract: An artificial middle ear prosthesis may be used to replace the ear structure from the bony ear canal up to the oval window of the vestibule. The artificial middle ear includes a tube to replace at least part of the bony ear canal, an annulus to connect an artificial ear drum to the tube, a complex structure to replace the hammer and anvil of a human patient and a piston means connected to the complex structure to replace at least part of the stirrup. According to one embodiment the piston may directly connect the complex hammer/anvil structure to the remaining portion of the oval window of the vestibule. According to another embodiment, the piston may be terminated in a cup shaped socket which will cradle the remaining structure of a stirrup. The bony ear canal tube, the umbo section connecting the complex hammer/anvil structure to the ear drum and the end of the piston directly contacting the stirrup or the oval window are preferably coated with a microporous biocompatible material such as Proplast. The ring or annulus is preferably formed from polytetrafluorethylene or a perfluorinated ethylene propylene polymer. The invention makes it possible to totally eradicate chronic otitis media without sparing the bony ear canal or bony annulus, by replacing the diseased tissues with the prosthesis described. Excerpt(s): This invention relates to an artificial middle ear and ear canal prosthesis. The efficient transmission of sound can be destroyed or substantially reduced by chronic otitis media. This disease can destroy part or all of the total middle ear system. It may even destroy parts of the bony external ear canal. The inner ear, the facial nerve and the brain may also run the risk of being attacked. In view of the foregoing it is desirable for a surgeon to remove the entire diseased area in order to avoid reoccurence. Such drastic surgery will frequently result in a substantial hole in the mastoid. Web site: http://www.delphion.com/details?pn=US04169292__

•

Auricular instrument Inventor(s): Schachar; Ronald A. (P.O. Box 124, Denison, TX 75020) Assignee(s): none reported Patent Number: 4,622,967 Date filed: September 13, 1984 Abstract: An auricular instrument (10) for the therapy of otitis media has a Q-switched laser (26) whose "giant pulse" output is especially suitable for forming a clean, round hole in a patient's tympanic membrane for draining the afflicted middle ear. The Qswitched laser (26) uses a neodymium YAG (yttrium-aluminum-garnet) lasing medium and its output is non-visible to the human eye. A gas laser (32) using a helium-neon lasing medium provides a low power, continuous beam of visible light upon which the output of the Q-switched laser (26) is made to ride by suitable optics. Both radiations

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emerge from the ear probe of a conically-tapering ear probe/cylindrical eyepiece (12) combination similar to that comonly found in otoscopes. With the probe being inserted in the patient's outer ear and with the eyepiece being looked through by a physician controlling the Q-switched laser (26), the physician will see a localized membrane area illuminated by the gas laser (32) and, as he controls the shots fired by the Q-switched laser (26), he will observe the progressive formation of the hole centrally of the localized area. Excerpt(s): This invention relates to auricular instruments and, more particularly, to an auricular instrument for the therapy of otitis media. Otitis media is a very common childhood infection involving inflammation of the middle ear marked by pain, fever, dizziness and abnormalities of hearing. It frequently requires surgical intervention when antibiotics are not sufficient to bring about recovery. Surgical intervention consists of making a surgical hole in the tympanic membrane, usually performed under general anesthesia. Tubes are placed in the hole for drainage of pus from the afflicted middle ear. The problems raised with the present surgery include: (1) the added risk to the patient with general anesthesia; (2) the necessity of making an appointment for the patient in a hospital for administration of the general anesthesia and surgery at considerable cost to the patient; (3) the usual requirement for the specialist services of an otolaryngologist to perform the operation, again at considerable cost; and (4) the inserted tubes may become blocked or fall out and thus require replacement. An aim of the invention is to provide an improved device for use in the therapy of otitis media. Web site: http://www.delphion.com/details?pn=US04622967__ •

Conjugate vaccine for nontypeable Haemophilus influenzae Inventor(s): Gu; Xin-Xing (Rockville, MD), Lim; David J. (Pasadena, CA), Robbins; John B. (Chevy Chase, MD), Tsai; Chao-Ming (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,207,157 Date filed: April 23, 1997 Abstract: A conjugate vaccine for Nontypeable Haemophilus influenzae comprising lipooligosaccharide from which esterified fatty acids have been removed conjugated to an immunogenic carrier. The vaccine is useful for prevention of otitis media and respiratory infections in mammals. Excerpt(s): The present invention relates to conjugate vaccines for prevention of bacterial infections. More specifically, the invention relates to a conjugate vaccine for nontypeable Haemophilus influenzae comprising lipooligosaccharide from which esterified fatty acids have been removed linked to an immunogenic carrier. Nontypeable Haemophilus influenzae (NTHi) is a major causative agent for acute otitis media (middle ear infections) and respiratory infections. Acute otitis media and otitis media with effusion are common childhood diseases, second in frequency of occurrence only to the common cold (Stool et al., Pediatr. Infect. Dis. Suppl., 8:S11-S14, 1989). The annual cost of the medical and surgical treatment of otitis media in the United States is estimated at between three and four billion dollars (Berman, New Engl. J. Med., 332:1560-1565, 1995). Moreover, inappropriate antibiotic treatment of otitis media can lead to the emergence of multidrug-resistant bacterial strains. There is currently no vaccine available for prevention of NTHi infection. Current efforts in developing an

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NTHi vaccine are focused on cell surface antigens such as outer membrane proteins and pili or fimbria (Kyd et al., Infect. Immun., 63:2931-2940, 1995; Deich et al., Vaccine Res., 2:31-39, 1995). Among these, the most promising is P6 protein which appears to be antigenically conserved and elicits the production of antibodies that are bactericidal in vitro. Lipooligosaccharide (LOS) is a major NTHi cell surface antigen. LOS contains both lipid A and oligosaccharide (OS) components. Because the lipid A component of LOS is toxic, it must be detoxified prior to conjugation to an immunogenic carrier. Web site: http://www.delphion.com/details?pn=US06207157__ •

Device and process for generating and measuring the shape of an acoustic reflectance curve of an ear Inventor(s): Busey; Hugh W. (Cheshire, CT), Combs; Jerome T. (Wallinford, CT), Ukraincik; Kresimir (Cromwell, CT) Assignee(s): MDI Instruments, Inc. (Woburn, MA) Patent Number: 5,699,809 Date filed: January 26, 1996 Abstract: A device and a process for analysis of acoustic reflectance of components of an ear directs into the ear canal acoustic waves covering a range of frequencies including resonance frequencies of ear components such as the tympanic membrane. Measurements are made without pressurizing the ear canal and contact between the device and the ear does not need to be air-tight. Accordingly, the patient experiences essentially no discomfort from use of the device. The device detects and combines the incident and reflected waves to produce what is called an acoustic reflectance curve. The shape of a region of the acoustic reflectance curve is electronically measured in order to obtain an indicator of ear condition which is substantially independent of a line of sight between a sound source and the tympanic membrane. This indicator is based on a measurement of the resonance characteristic, or freedom of motion, of the tympanic membrane or other ear component being analyzed. One such measurement is the rate of change of the acoustic reflectance with respect to frequency. Since resonance typically causes a null to appear in the acoustic reflectance curve, this measurement of the rate of change is particularly informative if measured around the null. The rate of change measured around the null may be presented as an angle measurement, a gradient or slope measurement, a width measurement, or other form of measurement of the shape of the null. In one embodiment, the steepest slopes on either side of a null are used to define an angle, herein called a spectral gradient. Diagnosis of an ear pathology, such as abnormal pressure or presence of fluid in the middle ear or such as conductive hearing loss, may be based on this measure alone. Because of the rate of change of an acoustic reflectance measurement is relatively constant for a given ear, regardless of the quality of the line of sight to the tympanic membrane, the effect, if any, of user training on such measurements is significantly reduced. Accordingly, the process and device of the invention are useful in many kinds of diagnostic situations with respect to ear pathology, but particularly in those involving screening of the ears of young children for common pathologies such as Otitis Media, even by untrained personnel. Excerpt(s): The present invention relates generally to devices and processes which provide information about a condition of an ear for use in diagnosis of ear pathologies. More particularly, the invention relates to devices and processes which involve measuring acoustic reflectance of components of the ear. A wide variety of diseases associated with the human and animal ears have been identified. The more frequently

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diagnosed pathologies include obstruction of the external ear canal, atresia of the external ear canal, perforation of the tympanic membrane, retraction of the tympanic membrane, otitis in its various forms (adhesive, purulent and non-purulent), otosclerosis, fixation of the stapes, and cholesteatoma, among others. In children, otitis media is one of the most common pathologies. By itself, otitis media is a significant affliction which can lead to serious long-term hearing and learning disabilities if not promptly diagnosed and treated. Further, otitis media is frequently symptomatic of other pathologies, and thus useful in their diagnosis. These ear pathologies are generally diagnosed using common diagnostic techniques, such as tympanometry, pneumatic otoscopy or visual otoscopy. While the usefulness of these techniques is well-recognized and established, these techniques do have some difficulties. For example, with both tympanometry and otoscopy, personnel who conduct tests and interpret results must be highly trained. Since these techniques cannot be performed by non-medical or inexperienced personnel, efficient screening of children or infants at home or in a school is not possible with these techniques. Web site: http://www.delphion.com/details?pn=US05699809__ •

DNA molecules which encode the fimbrin protein of Haemophilus influenzae Inventor(s): Bakaletz; Lauren O. (Columbus, OH), Kolattukudy; Pappachan E. (Columbus, OH), Sirakova; Tatiana (Columbus, OH) Assignee(s): The Ohio State Research Foundation (Columbus, OH) Patent Number: 5,766,608 Date filed: June 1, 1995 Abstract: It has been discovered that a vaccine comprised of fimbrin, a filamentous protein derived from the bacterial surface appendages of non-typable Haemophilus influenzae is useful in studying, preventing or reducing the severity of, otitis media. The gene sequence of the DNA coding for fimbrin and the amino acid sequence of fimbrin have also been determined. Vectors containing DNA coding for fimbrin have also been developed, and transformants have been prepared which contain such vectors and which express such DNA and provide a source of pure fimbrin. Excerpt(s): Otitis media is an infection of the middle ear that occurs primarily in children. Left untreated, the disease can result in hearing loss, and developmental delays. It is estimated that otitis media accounted for 31 million of the 130 million office visits for respiratory diseases in the period from 1987-87. Recent data indicate that suppurative and unspecified otitis media rank first in the list of the 30 most common diagnoses requiring a physician's office visit for patients up to age 24. Over one billion dollars per year is spent on treatment of this disease and the related loss of income for working parents is estimated to be between $300 and $600 million. Approximately 83% of all children by three years of age will have had at least one episode of acute otitis media. Non-typable strains of Haemophilus influenzae account for 25-30% of all cases of otitis media, 53% of recurrent otitis media, and are the primary pathogens isolated from 62% of cases of chronic otitis media with effusion. Although non-typable Haemophilus influenzae (NTHi) are primary pathogens in otitis media, neither the pathogenic mechanisms nor the host immunological response has been fully defined for this disease. It would be desirable to have a vaccine to confer immunity to non-typable Haemophilus influenzae or to reduce the severity of otitis media caused by Haemophilus influenzae.

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Web site: http://www.delphion.com/details?pn=US05766608__ •

Ear pathology diagnosis apparatus and method Inventor(s): Teele; John H. (22 Ruthellen Rd., Chelmsford, MA 01824) Assignee(s): none reported Patent Number: 4,459,996 Date filed: March 16, 1982 Abstract: The present invention provides a method and apparatus for diagnosis of various ear pathologies, including the diagnosis of effusions of the middle ear associated with Otitis Media. The method is practiced by determining a quantity related to the complex acoustic impedance of the ear, namely the Vector Sum of an incident signal, propagating down the ear canal, and the same signal reflected from the tympanic membrane and middle ear components. The results obtained are compared with the expected results of a healthy ear. Excerpt(s): The present invention relates generally to devices and methods for diagnosis of pathological ear conditions, and particularly to those devices and methods in which there are determined quantities related to the complex acoustic impedance of components of the ear. See also Pinto and Dallos, "An Acoustic Bridge for Measuring the Static and Dynamic Impedance of the Ear Drum", IEEE Transactions on Bio-Medical Engineering, Volume PME-15, No. 1, January 1968, pages 10-16. Typically, a probe such as that described in U.S. Pat. No. 4,057,051 (Kerovac), is inserted into the ear canal in such a way that the ear is effectively sealed from the external atmosphere. The probe is usually supplied with a means for varying the pressure within the ear canal above and below ambient pressure. Web site: http://www.delphion.com/details?pn=US04459996__

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Ear pathology diagnosis apparatus and method Inventor(s): Teele; John H. (22 Ruthellen Rd., Chelmsford, MA 01824) Assignee(s): none reported Patent Number: 4,601,295 Date filed: November 15, 1983 Abstract: A method and apparatus for diagnosing pathologies of the ear, particularly pathologies such as otitis media, directs into the ear canal a sequence of acoustic waves covering a range of frequencies from a few hundred Hz to several kHz and determines the presence or absence of resonance when the incident and reflected waves are combined. The measurements are made without pressurizing the ear canal and it is not required that the contact between the instrument and the ear be air-tight. Accordingly, essentially no discomforture of the patient results from use of the instrument. The requisite measurements are made quickly (of the order of tens of milliseconds) and thus the distorting effects of patient movement are effectively eliminated. An improved version of the instrument is completely self-contained and hand-held and has the form of a "tee" in which the resonant frequency and amplitude are visually indicated by means of horizontally-and-vertically disposed arrays of light-emitting diodes.

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Excerpt(s): The present invention relates generally to devices and methods for diagnosis of pathological ear conditions, and particularly to those devices and methods in which there are determined quantities related to the complex acoustic impedance of components of the ear. A wide variety of specific pathologic diseases associated with the human and animal ear have been identified. Among the more frequently identified pathologies are those comprising obstruction of the external canal, agenesis of the pinna, atresia of the external canal, perforation of the tympanic membrane, retraction of the tympanic membrane, otitis in its various forms (adhesive, purulent and non-purulent), otosclerosis, fixation of the stapes, and cholesteatoma, among others. In children, otitis media is one of the most common childhood pathologies. By itself, it is a significant affliction which can lead to serious long-term hearing and learning disabilities if not promptly diagnosed and treated. Further, it is frequently symptomatic of other pathologies, and thus useful in their diagnosis. The diagnosis of otitis media in young children is particularly difficult because of the fear, or even pain, associated with the commonly available techniques of diagnosis. The usefulness of examination by conventional otoscopic techniques is often diminished by the discomfort of the child which leads, at best, to movement by the child which impairs the examination and, at worst, to a refusal to allow the examination to proceed. The problem is especially acute when the examination is to be made in the environment of a mass screening, such as may take place in hospital clinics where large numbers of patients must be seen in a comparatively short time. Similar problems are encountered in the useage of other diagnosis techniques, such as tympanometry. Web site: http://www.delphion.com/details?pn=US04601295__ •

Immortalized human middle ear epithelial cell lines Inventor(s): Brackmann; Derald E. (South Pasadena, CA), Chun; Young-Myoung (Kyungki-Do, KR), Lim; David J. (Pasadena, CA), Rhim; Johng S. (Potomac, MD) Assignee(s): House Ear Institute (Los Angeles, CA) Patent Number: 6,358,688 Date filed: May 26, 2000 Abstract: Human middle ear epithelial cell lines permanently transformed by human papilloma viruses have been obtained. These cell lines are useful for the study of gene and protein expression in otitis media and the identification of chemical and biological agents that may be useful in the therapy of human otitis media and other diseases of the ear. Excerpt(s): The present invention relates to novel immortalized middle ear epithelial cell lines and their use in screening assays. Otitis media (OM), or inflammation of the middle ear, is the second most frequent illness resulting in visits to physicians following the common cold and the most common cause of hearing impairment in children. According to the Centers for Disease Control and Prevention/National Center for Health Statistics, OM accounts for an estimated 31 million annual visits to the doctor's office. Eighty percent of the children born each year experience at least one episode of OM by their third birthday, and one in three have repeated bouts of the disease. Although the fraction of health care expenditure taken up by OM is unknown, it is estimated to have a yearly cost exceeding $5 billion. Acute OM (AOM) generally refers to the rapid onset of signs and symptoms of an acute infection in the middle ear. Chronic otitis media with effusion (OME), also known as persistent middle ear effusion, is the major sequela of acute OM. OME is characterized by the accumulation of serous,

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mucoid or purulent fluid in the middle ear space, without compromising the intactness of the tympanic membrane (Bluestone, C. and Klein, J O. 1995. Otitis media in infants and children: W.B. Saunders Company). In approximately 40% of the cases, middle ear effusion can still be seen one month after antibiotic treatment and in 20% of them, even after three months. In the US alone, about one million tympanostomy tubes are inserted per year, for the treatment of persistent or recurring OM. The course of OME is generally benign and self-limiting. The deafness caused by the effusions, however, if not treated in time, could adversely affect the child's development and educational progress. Web site: http://www.delphion.com/details?pn=US06358688__ •

Intraoral administration device and system Inventor(s): Aaltonen; Antti Sakari (Marttilantie 2as.6, FIN-03850 Pusula, FI), Suhonen; Jouko (663 Garth Ct., Yorktown Heights, NY 10598) Assignee(s): none reported Patent Number: 5,993,413 Date filed: September 3, 1998 Abstract: An intraoral administration device having an elongated, substantially platelike arcuate oral screen designed to conform to the teeth and intended to be accommodated in the space between the teeth and the lips. The oral screen includes containers for the agent to be administered intraorally, which containers have provision for allowing the free entrance of saliva into the container and its exit therefrom. An administration system using the administration device and an active agent, such as for example an agent against caries or otitis media is also contemplated. Excerpt(s): The object of the present invention is an intraoral administration device comprising an elongated, substantially plate-like curved oral screen designed to conform to the teeth and intended to be positioned in the space between the teeth and the lips. The object of the present invention is also an administration system, which comprises the administration device according to the invention in combination with an active agent. By means of the administration system according to the invention it is possible to provide a sustained local therapeutic effect in the region of the mouth and throat which is adapted to take into account the eruption order of the teeth and the location of the salivary glands, while simultaneously satisfying the physiological sucking need and craving for sweetness of small children, using small dosage levels tolerated by children and without causing malocclusions, especially when the sucking need of the child continues too long from the orthodontic point of view. Various dispensing pacifiers are known (for example U.S. Pat. No. 4,078,566, GB-patent application 2 181 957A; EP Pat. No. 0 494 904, FI-patent application FI-A 921411, U.S. Pat. No. 5,395,392; and the commercially available CANNON babysafe Minifeeder). Suhonen (1992) has presented the theoretical background for the use of a pacifier like administration device which slowly releases fluorides, xylitol, monoclonal caries antibodies or lactoperoxidase enzyme components into the mouth, in a prophylactic method for the prevention of dental caries. The operability of a dispensing pacifier for releasing sodium fluoride, xylitol and sorbitol from a tablet has been established in vitro, and the administration from a pacifier of passive vaccines against microbes causing oral diseases has been suggested (Suhonen at al, 1994). A pacifier prototype for dispensing sodium fluoride, xylitol and sorbitol has in our field trial with children of the age of 16 months proved to be a functioning weans with potential for development for the treatment of diseases of the mouth and throat of children in the sucking-age. In our

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follow-up study it also became evident that in the group of children that had accepted the test pacifier, there appeared significantly less often infection of the middle ear (otitis media, 48% versus 70%) than in the comparison group. Recently it has been shown that xylitol also inhibits the growth of Streptococcus pneumoniae (pneumococcus) (kontiokari et al 1995). According to one report (October 1996) the use of a xylitol bubble gum several times a day has reduced infection in the middle ear in kindergarten children in Oulu. The mouth cavity can thus be an area of primary defense in the battle against bacteria aiming for the middle ear. Web site: http://www.delphion.com/details?pn=US05993413__ •

Method of treating otitis media with uridine triphosphates and related compounds Inventor(s): Drutz; David J. (Houston, TX), Jacobus; Karla M. (Cary, NC), Rideout; Janet L. (Raleigh, NC) Assignee(s): Inspire Pharmaceuticals, Inc. (Durham, NC) Patent Number: 6,423,694 Date filed: February 21, 1996 Abstract: A method of promoting drainage of congested middle ear fluid in a subject in need of such treatment is disclosed. The method comprises administering to the middle ear of the subject a uridine triphosphate such as uridine 5'-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to promote drainage of congested middle ear fluid by hydrating mucous secretions in the middle ear or by stimulating ciliary beat frequency in the middle ear or eustachian tube. The method is useful for treating patients afflicted with otitis media and other middle ear diseases, otitis externa, and inner ear diseases including Meniere's Disease. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal drops or spray), oral, inhaled by nebulization, topical, injected or suppository form. Excerpt(s): This invention relates to a method of removing or preventing the accumulation of retained mucous secretions from the middle ear of a patient by administering certain uridine, adenosine, or cytidine triphosphates. Otitis media (OM) is a viral or bacterial infection of the middle ear primarily, but not exclusively, afflicting children under three years of age. It is characterized by the presence of congested fluid in the middle ear and is usually precipitated by an infection in the respiratory tract which spreads into the middle ear via the nasopharnyx and eustachian tube. The incidence of OM is increasing--annual physician's office visits for OM have increased 150% from 1975 through 1990 (L. McCraig and J. Hughes, JAMA 273(3), 214-19 (1995)). This is most likely due to increased use of large-group day care facilities, where children are exposed to more respiratory pathogens. Approximately 25-40 million office visits are made each year for diagnosis and treatment of OM, and by age three, approximately 75% of children will have had at least one episode of acute OM (with the maximum incidence in children 6-24 months of age) (J. Klein, Clin Infect Dis 19, 823-33 (1994)). Anatomically, the eustachian tubes in infants are shorter, wider, and lie more horizontally than in older children and adults, facilitating the spread of pathogens from the nasopharnyx to the middle ear (L. Schwartz and R. Brown, Arch Intern Med 152, 2301-04 (1992)). The infection evokes an inflammatory response in the mucosal tissue of the eustachian tube and middle ear, resulting in fluid effusion in the middle ear. The resulting fluid is viscous and pus-filled, making normal mucociliary movement of the fluid difficult, and inflammation of the eustachian tube at its narrowest point, the

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isthmus, effectively blocks drainage of the fluid into the nasopharnyx (J. Klein, supra (1994)). Middle ear congestion can be expected to cause significant pain, dizziness, and hearing impairment in the patient; the average hearing loss from the fluid accumulation is 25 decibels. This is of particular concern in very young children because impairment of hearing could delay or seriously impede aspects of normal cognitive development which are dependent upon exposure to language and social interaction (D. Teele, et al. J. Infect Dis 1621, 685-94 (1990)). Other potential (but uncommon) sequelae of OM include mastoiditis, meningitis, extradural abscess, subdural empyema, brain abscess, and lateral sinus thrombosis. About 80-90% of OM effusions eventually resolve spontaneously following antibiotic therapy; the process may take as long as three months. However, congestion in the middle ear may persist for weeks or even months beyond sterilization of this fluid with antibiotics due to a continued hypersecretory state of the mucous-producing cells. (S. Wintermeyer and M. Nahata, Annals of Pharmocotherapy 28, 1089-99 (1994)). The cause of this persistent hypersecretory state is not well understood but may relate to unrelieved underlying eustacian tube obstruction. As a further impediment to treatment, the effectiveness of antibiotic therapy is decreasing on account of growing bacterial resistance to antibiotics (M. Poole, Pediatr Infect Dis J. 14(4), 523-26 (1995)). If middle ear congestion persists for more than three months, surgery is commonly performed to insert a typanostomy tube to ventilate the middle ear of the patient (K. Grundfast, Arch Otolaryngol Head Neck Surg, 120, 797-98 (1994)). Tympanostomy surgery is now the second most frequent surgical procedure in children (after circumcision) (J. Klein, supra (1994)). The tube allows drainage of the fluid out of the ear and eventual resolution of the disease in a vast majority of chronic cases. However, the surgery is costly (>$2,000), and requires administering general anesthesia, a particular concern in infant patients. Furthermore, potential (but uncommon) sequelae of the surgery include persistent otorrhea, permanent perforation or scarring of the tympanic membrane, and cholesteatoma (a cyst-like sac filled with keratin debris that can occlude the middle ear and erode surrounding structures) (J. Klein, supra (1995)). Web site: http://www.delphion.com/details?pn=US06423694__ •

Method of treating respiratory infections or complications derived therefrom in humans which includes oral administration of xylitol Inventor(s): Kontiokari; Tero Tapani (Oulu, FI), Uhari; Matti Kalervo (Oulu, FI) Assignee(s): Leiras Oy (Turku, FI) Patent Number: 5,719,196 Date filed: July 24, 1996 Abstract: A new use of xylitol is disclosed. The invention relates to a method of treating respiratory infections, especially acute otitis media, in humans which method comprises oraly administering to the human an effective amount of xylitol. Excerpt(s): The present invention relates to a means of treating respiratory infections in humans, and, more particularly, to a method of preventing acute otitis media involving oral administration of xylitol. The present invention relates to the use of xylitol for the treatment of respiratory infections, especially acute otitis media, in humans. The present invention is based on the surprising discovery that xylitol exhibits a growth inhibiting effect against pneumococci which reduces the pneumococcal carriage rates and also reduces the incidence of acute otitis media. In accordance with the present invention

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there is provided a method of treating respiratory infections in humans which comprises orally administering to the human an effective amount of xylitol. Web site: http://www.delphion.com/details?pn=US05719196__ •

Methods and compositions for treating sinusitis, otitis media and other related disorders using antihistamines Inventor(s): Johnson; Nancy R. (Westfield, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,297,227 Date filed: September 9, 1999 Abstract: The present invention discloses antibiotic-excluded compositions and methods to treat non-infective sinusitis and otitis media. The compositions comprise a therapeutically effective amount of a corticosteroid, and the methods comprise administering a pharmaceutical composition comprising a therapeutically effective amount of a corticosteroid. Preferred corticosteroids are mometasone furoate and mometasone furoate monohydrate. Excerpt(s): The present invention generally relates to methods of treating sinusitis and otitis media (including otitis media with effusion and persistent middle ear effusion) involving the administration of a therapeutically effective amount of a corticosteroid. It specifically relates to such treatment involving the administration of a therapeutically effective amount of mometasone furoate. The subject matter of this patent application is related to that disclosed in pending U.S. patent applications, Ser. No. 09/391,795 filed of even date herewith, Ser. No. 08/376,506, filed Jan. 23, 1995, and Ser. No. 07/984,573, filed Apr. 29, 1998. Sinusitis is the most frequently reported chronic disease in the United States, affecting more than 14% of the population. Sinusitis is an inflammation of the mucosa of the paranasal sinuses. Generally, there is an allergic cause to sinusitis. Otitis media, like sinusitis, is also generally considered to have an allergic cause. These are also characterized by retention of thickened respiratory secretions; however, the inflammation is manifest in the ear rather than in the sinuses. A discussion of sinusitis and otitis media can be found in Conn's Current Therapy, 235 (1997); Diseases of the Sinuses--A Comprehensive Textbook of Diagnosis and Treatment, ed. M. E. Gershwin et al, Human Press, Totowa, N.J., pages 151-157 (1996); and Allergy--Principles and Practice, Volume II, ed. E. Middleton, Jr. et al, Mosby-Year Book, Inc., New York, pages 1027-1033 (1998). Also, a review of sinusitis and related facts is given by Z. Pelikan, "The Role of Allergy in Sinus Disease", Clinical Reviews in Allergy and Immunology, 16, 55156 (1998). Sinusitis and otitis media are often typically treated as infectious diseases. The treatment typically includes administration of an antibiotic along with a corticosteroid and an antihistamine, or a nasal decongestant. such as described in, for example, J. Braun et al, Allergy, 52 (6) 650-655 (1997). There are, however, occasions, when the sinusitis or otitis media is not necessarily accompanied by an infection. This is particularly true when the disease is associated with allergic rhinitis. At those times, administration of an antibiotic may not be needed. Physicians, however, do not generally administer corticosteroids for these indications without accompanying antibiotic. Web site: http://www.delphion.com/details?pn=US06297227__

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Nasal delivery of xylitol Inventor(s): Behl; Charanjit R. (Hauppauge, NY), Romeo; Vincent D. (Massapequa, NY) Assignee(s): Nastech Pharmaceutical Company, Inc. (Hauppauge, NY) Patent Number: 6,599,883 Date filed: October 29, 1999 Abstract: The present invention is a method and pharmaceutical composition for prevention and/or treatment of upper respiratory infections including otitis media by nasal administration of xylitol. Excerpt(s): The present invention relates generally to the art of intranasal delivery of bio-effecting agents to a mammal and, in particular, to an intranasal treatment and composition which rely on the effects of sugar alcohols, especially xylitol. Sugar alcohols, also known as polyols, are utilized in a variety of fields. The use of these polyhydric alcohols, such as sorbitol, mannitol, and xylitol, as non-fermentable carbohydrates in place of sucrose and other sugars in chewing gums and confections is known. For the most part sugar alcohols have been known and used based on their unique, substantially non-nutritional sweetening properties. For example, xylitol, which is a five carbon chain classified as a polyol or sugar alcohol (commonly known as birch sugar because it can be derived from birch), is used as a sweetener because it possesses a sweetness equivalent to that of sucrose. Due to its five-carbon sugar alcohol structure, xylitol is unsuitable as a source of energy for most oral microorganisms. Regular consumption of xylitol has also been shown to reduce the incidence of dental caries. This is primarily attributed to xylitol's ability to inhibit and/or reduce the growth and acid production of S. mutans, which is the most important bacterium taking part in the pathomechanism of dental caries. Web site: http://www.delphion.com/details?pn=US06599883__

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Nasopharynx administration of mupirocin for prophylactic treatment of recurrent otitis media Inventor(s): Henkel; Timothy John (Cambridge, GB) Assignee(s): SmithKline Beecham Corporation (), SmithKline Beecham p.l.c. (GB) Patent Number: 6,001,870 Date filed: September 30, 1997 Abstract: Mupirocin or a salt or ester thereof may be used to treat recurrent sinusitis and recurrent otitis, in particular with novel spray or cream formulations adapted for administration to the nasopharynx. Excerpt(s): The present invention relates to the use of mupirocin or a salt or ester thereof in treating certain bacterial infections, in particular recurrent otitis media and recurrent sinusitis, and to formulations for use in such treatment. Mupirocin, formerly known as pseudomonic acid, is a therapeutically useful compound which exhibits good antibacterial activity, mainly against Gram-positive bacteria, but also against some Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis. It acts as a selective reversible inhibitor of bacterial iso-leucyl t-RNA synthetase, thereby inhibiting bacterial protein synthesis (see Merck Index, 11th edn, 1989, 993 and references therein). The compound has an ester moiety which is susceptible to metabolism, effectively excluding the systemic use of the compound. It is however

Patents 177

clinically effective as a topical agent. Topical antibacterial compositions comprising mupirocin are marketed by SmithKline Beecham under the trade names Bactroban Ointment and Bactroban Nasal. The first product is an ointment comprising a water soluble polyethylene glycol base (see also EP 0 095 897-A, Beecham Group) whilst the second product comprises the calcium salt of mupirocin in a white soft paraffin based ointment containing a glycerin ester (see also EP 0 167 856-A, Beecham Group). More recently, topical creams comprising mupirocin or a salt thereof have been described (PCT/US94/12026, SmithKline Beecham). The formulation comprising the calcium salt of mupirocin in a white soft paraffin based ointment containing a glycerin ester (Bactroban Nasal) is particularly useful when applied to the anterior nares for the prophylactic eradication of the nasal carriage of Staph aureus. More recently, it has been found that the impact of such application is limited to the anterior nares. There is no significant reduction in the colonisation (by H. influenzae, S. pneumonia and M. catarrhalis) of the nasopharynx (unpublished). Web site: http://www.delphion.com/details?pn=US06001870__ •

Pharmaceutical and dietary composition Inventor(s): Horrobin; David F. (Montreal, CA) Assignee(s): Efamol Limited (Surrey, GB2) Patent Number: 4,681,896 Date filed: January 31, 1984 Abstract: A method of treatment of atopic disorders, including eczema, asthma, allergies (especially allergic rhinitis), migraine and disorders associated with atopy including Crohn's disease, ulcerative colitis, otitis media, nephrotic syndrome, or benign breast disease, or breast or other cancer, or diabetes, or alcoholism, with effective amounts of one or more of the metabolites of linoleic acid (GLA, DGLA, AA, 22:4n-6 or 22:5n-6) and one or more of the metabolites of.alpha.-linolenic acid (18:4n-3, 20:4n-3, 20:5n-3, 22:5n-3 or 22:6n-3) are administered as such or in the form of an ester, salt, amide or other derivative convertible in the body thereto alone or in an acceptable pharmaceutical carrier or diluent. Excerpt(s): This invention relates to the treatment of certain diseases and disorders primarily, but not exclusively, in the field of human medicine and to compositions for use therein. The essential fatty acids (EFAs) are of two types, the n-3 or (.omega.-3) series derived from.alpha.-linolenic acid and the n-6 (or.omega.-6) series derived from linoleic acid. Linoleic acid and.alpha.-linolenic acid are like vitamins in that they cannot be manufactured in the body and therefore must be provided in the diet. The body can metabolise them along the pathways below and such metabolism is believed to be essential if they are to fulfil their functions. The acids are in the natural all-cis configurations. In the n-6-series commonly used names for the 18:2, 18:3, 20:3, 20:4 and 22:4 acids are linoleic acid,.gamma.-linolenic acid (GLA), dihomo-.gamma.-linolenic acid (DGLA), arachidonic acid (AA) and adrenic acid. In the n-3 series only.alpha.-linolenic acid (18:3) is commonly referred to by a non-systematic name. Web site: http://www.delphion.com/details?pn=US04681896__

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Pharmaceutical composition and process for preparing the same Inventor(s): Bacsa; Gyorgy (Debrecen, HU), Barna nee Katona; Klara (Debrecen, HU), Katona nee Lendvay; Agnes (Debrecen, HU), Kincses; Gyula (Debrecen, HU), Kocsar; Barna (Debrecen, HU), Kovacs; Istvan (Debrecen, HU), Krusper; Laszlo (Debrecen, HU), Lampe; Istvan (Debrecen, HU), Szabo; Csongor (Debrecen, HU), Trestyanszky; Zoltan (Debrecen, HU) Assignee(s): Biogal Gyogyszergyar (Debrecen, HU) Patent Number: 5,061,729 Date filed: June 8, 1988 Abstract: The invention relates to pharmaceutical compositions as well as the preparation thereof which are useful for improving the status of patients suffering from external otitis or otitis (otitis media), or particularly from a chronic otitis (otitis media chronica). The pharmaceutical compositions according to the invention contain a sulfhydryl-containing compound, an antibacterial chemotherapeutic agent, an aspecific antiinflammatory agent and optionally a kerotolytic agent. The compositions preferably contain N-acetyl-L-cysteine as sulfhydryl-containing compound. Excerpt(s): This invention relates to novel pharmaceutical compositions useful for improving the status of patients suffering from external otitis or otitis (otitis media), particularly from a chronic otitis (otitis media chronica) as well as for restoring the healthy conditions of the middle ear. According to an other aspect of the invention, there is provided a process for the preparation of the novel compositions. Chronic otitis is a diasease occurring in both adult age and childhood which affects a relatively high percentage of the population. Not only the acute complications but also the bradyacusia (hardness of hearing) and surdity emerging later on can be avoided by an early diagnosis and suitable therapy. The deterioration of hearing of about one fourth of all the patients suffering from hardness of hearing can be attributed to inflammations endured in childhood and developing frequently in connection with infective diseases. Both the subacute and chronic otitis are found in a higher percentage of children who frequently suffered from otitis. Essential characteristics of this desease are a discontinuity of the eardrum, alterations of the tympanic cavity and recurrent recrudescences of the symptoms. In addition to the common reacions following the imflammation, the local symptoms may be manifest or latent. In the absence of therapy, these processes may lead to life-threatening complications. Web site: http://www.delphion.com/details?pn=US05061729__

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Pharmaceutical composition for preventing and treating allergic diseases and a method for preparation thereof Inventor(s): Hwang; Woo-Jun (Cheollabook-do, KR), Jang; Chul-Ho (Jeollabook-do, KR), Kim; Hyung-Min (Cheollabook-do, KR), Park; Eun-Jeung (Cheollabook-do, KR) Assignee(s): Biomedpark Co., Ltd. (Yongin, KR), Daehan Biolink Co., Ltd. (Chungbuk, KR) Patent Number: 6,524,627 Date filed: March 20, 2002 Abstract: This invention relates to a pharmaceutical composition comprising Platycodi Radix, Scutellariae Radix, Ponciri Fructus, Schizonepetae Herba, Bupleuri Radix,

Patents 179

Angelicae dahuricae Radix, Paeoniae Radix alba, Cnidii Rhizoma, Angelicae gigantis Radix, Ledebouriellae Radix, Forsythiae Fructus, Glycyrrhizae Radix, Lonicerae Flos, Taraxaci Herba, Trichosanthis Radix, Ulmi Cortex Radicis, Astragali Radix, Atractylodis Rhizoma alba, Rehmanniae Rhizoma, Zanthoxyli Fructus, Magnoliae Flos, Xanthii Fructus, Mori Cortex Radicis, Pinelliae Tuber, Cimicifugae Rhizoma, Puerariae Radix and Menthae Herba as the active ingredients for preventing and/or treating acute and/or chronic allergic nasal diseases (including chronic paranasal sinusitis), allergic dermatitis, allergic otitis media (including recurrent otitis media with effusions), allergic conjunctivitis, allergic asthma, etc., and to a method for preparation thereof. Excerpt(s): This invention relates to a pharmaceutical composition for preventing and treating allergic diseases and to a method for preparation thereof. Specifically, the present invention relates to a pharmaceutical composition comprising Platycodi Radix, Scutellariae Radix, Ponciri Fructus, Schizonepetae Herba, Bupleuri Radix, Angelicae dahuricae Radix, Paeoniae Radix alba, Cnidii Rhizoma, Angelicae gigantis Radix, Ledebouriellae Radix, Forsythiae Fructus, Glycyrrhizae Radix, Lonicerae Flos, Taraxaci Herba, Trichosanthis Radix, Ulmi Cortex Radicis, Astragali Radix, Atractylodis Rhizoma alba, Rehmanniae Rhizoma, Zanthoxyli Fructus, Magnoliae Flos, Xanthii Fructus, Mori Cortex Radicis, Pinelliae Tuber, Cimicifugae Rhizoma, Puerariae Radix and Menthae Herba as the active ingredients for preventing and/or treating acute and/or chronic allergic nasal diseases (including chronic paranasal sinusitis), allergic dermatitis, allergic otitis media (including recurrent otitis media with effusions), allergic conjunctivitis, allergic asthma, etc., and to a method for preparation thereof. A normal immune reaction may cause local inflammations or eliminate foreign substance without damaging tissues of their hosts by stimulating effective molecules to remove attacks from allergen through various mechanisms. However, the term of hypersensitivity or allergy is used when an immune reaction is excessively activated or progressed in an undesirable direction to harm the human body. Today, allergic diseases cost a lot of money, because they tend to be more severe in civilized societies. According to a literature [Scientific American, September, 1993], more than 20% of American people are suffering from various allergic symptoms, and allergic rhinitis is the most common form of allergy. The attack of allergen can sometimes be fatal. According to the statistical data of 1990, it was reported that 3.6 billion dollars had been spent to the direct medical cost for asthma. As to the number of patients who are suffering from these allergic diseases, Korea is also on the similar level to the developed countries. The number is increasing every year. In particular, young child patients are on rapid increase. Thus, many researchers are devoting themselves in developing a drastic cure to reduce economic, biological and physical burden of the patient from such allergic diseases. It might be said that diversity and complexity of allergic diseases are from the exposure to many kinds of allergen in the modern life. Synthetic fibers such as nylon and Teflon, and synthetic resins such as polyethylene, polyester and epoxy resin, which brought innovation to the textile industry, cause anaphylactic contact dermatitis at skin or mucous membrane by various chemical substances like monomer and polymer that are produced in the manufacturing process. On the other hand, allergic inflammations on the skin are caused by contact with glass frames, artificial teeth, wrist watch chains, plastic raincoats, umbrella handles, etc. The substances such as polyurethane, which are widely used as paints for cars, furniture and musical instruments, are the main cause of bronchial asthma. Rubber, leather, cement, and metals such as platinum, gold, mercury and nickel may cause allergic contact dermatitis. Accessories, such as earrings, necklace and finger rings, or rubber products, may also cause allergy. It is well known that fast food, antiseptic, synthetic sweetening, and additives including food colors may also cause food allergy.

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Web site: http://www.delphion.com/details?pn=US06524627__ •

Product for inhibition of attachment of H. influenzae to human cells Inventor(s): Anderson; Steven Neal (Pickerington, OH), Harvey; Linda Ann (Orient, OH), Mukerji; Pradip (Gahanna, OH), Seo; Amanda Eun-Yeong (Gahanna, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,643,880 Date filed: May 26, 1994 Abstract: The attachment of H. influenzae to human cells, such as oropharyngeal cells, may be inhibited by native human.beta.-casein, a recombinant form of human.beta.casein, and hydrolysates of both. The human.beta.-casein or hydrolysate may be contained in a liquid enteral nutritional product such as an infant formula. The enteral nutritional product may be used, for example, in the prevention and treatment of otitis media in infants. The human.beta.-casein or hydrolysate may also be administered as a throat spray or nasally using drops or a spray. Excerpt(s): The present invention relates generally to inhibiting the attachment of Haemophilus influenzae to human cells, and more specifically to the use of native or recombinant human.beta.-casein and hydrolysates thereof for inhibiting the attachment of Haemophilus influenzae (H. influenzae) to human cells. Haemophilus are small, gram-negative, non-molotile, non-spore forming bacilli with complex growth requirements. Diseases caused by H. influenzae usually begin as a nasopharyngitis, possibly precipitated by a viral infection of the upper respiratory tract. Morse, et al. "Haemophilus", MICROBIOLOGY, FOURTH EDITION, published by J. B. Lipincott Company, pages 615-618 (1990). H. influenzae are spread from person to person by airborne respiratory droplets or direct contact with secretions. To colonize, H. influenzae must contend with ciliary clearance mechanisms of the nasopharyngeal mucosal surface and the mucous barrier. Once past the mucous barrier and the ciliary escalator, H. influenzae attach to mucosal epithelial cells. Invasion of mucosal surfaces appears to be an important characteristic of pathogenic bacteria. Stephens, et al., "Pathogenic Events During Infection of the Human Nasopharynx with Neisseria meningitis and Haemophilus influenzae", REVIEWS OF INFECTIOUS DISEASES, 13:2223 (1991). It has further been reported that H. influenzae harbored in the nasopharynx are a key factor in the development of middle ear infections (otitis media), and that nontypable H. influenzae adhere to nasopharyngeal and nasal mucosal cells. Harada et al., "Adherence of Haemophilus influenzae to nasal, nasopharyngeal and bucal epithelial cells from patients with otitis media" EUROPEAN ARCHIVES OF OTO-RHINOLARYNGOLOGY, 247:122-124 (1990). Stenfors et al., "Abundant Attachment of Bacteria to Nasopharyngeal Epithelium in Otitis-Prone Children", THE JOURNAL OF INFECTIOUS DISEASES, 165:1148-1150 (1992). In accordance with the present invention.beta.-casein isolated from human milk or a recombinant form thereof, or a hydrolysate of either is employed to inhibit the adhesion of H. influenzae to human cells. Web site: http://www.delphion.com/details?pn=US05643880__

Patents 181

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Therapeutic dinucleotide and derivatives Inventor(s): Boucher, Jr.; Richard C. (Chapel Hill, NC), Pendergast; William (Durham, NC), Picher; Maryse (Carrboro, NC), Rideout; Janet L. (Raleigh, NC), Stutts; M. Jackson (Chapel Hill, NC), Yerxa; Benjamin R. (Raleigh, NC) Assignee(s): Inspire Pharmaceuticals, Inc. (Durham, NC), University of North Carolina at Chapel Hill (Chapel Hill, NC) Patent Number: 6,323,187 Date filed: May 21, 1999 Abstract: The present invention relates to P.sup.1 -(cytidine 5'-)-P-(uridine 5')tetraphosphates and its salts, esters and amides, and formulations thereof which are highly stable and selective agonists of the P2Y.sub.2 and/or P2Y.sub.4 purinergic receptor. The compounds of the invention are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, primary ciliary dyskinesia, cystic fibrosis, as well as prevention of pneumonia due to immobility, and the induction of sputum and its expectoration. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis and otitis media. Excerpt(s): This invention relates to a method of enhancing clearance of secretions by increasing the hydration of retained mucus secretions, stimulating the production of mucins, and increasing ciliary beat frequency by administering P.sup.1 -(cytidine 5'-)P.sup.4 -(uridine 5'-)-tetraphosphate (CP.sub.4 U) or pharmaceutically acceptable esters, amides or salts thereof. Chronic obstructive pulmonary disease (COPD) affects 15 million patients in the U.S. and is the sixth leading cause of death. It is characterized by the retention of mucus secretions in the lungs which results in progressive lung dysfunction over time. Many patients diagnosed with COPD have a disorder called chronic bronchitis (CB), and 600,000 patients are hospitalized each year due to an acute exacerbation of CB. Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are other examples of lung disorders which assume a clinical profile similar to COPD. Ciliary dyskinesia, whether primary or secondary, results in retained secretions that can only be cleared by coughing. Most patients with COPD utilize coughing to help clear retained secretions because of impaired mucociliary clearance. Another disease state characterized by the accumulation of retained mucous secretions is sinusitis. Sinusitis is an inflammation of the paranasal sinuses typically associated with an upper respiratory infection. It can occur as either an acute or chronic condition. It is this country's most common health-care complaint, affecting an estimated 31 million people. (A. Moss and V. Parsons, National Center for Health Statistics, 1986: 66-7, DHHS Publication No. (PHS)86-1588 (1985)). Web site: http://www.delphion.com/details?pn=US06323187__

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Treatment of autonomic nerve dysfunction with botulinum toxin Inventor(s): Sanders; Ira (New York, NY), Shaari; Christopher M. (New York, NY) Assignee(s): Mount Sinai School of Medicine of the City University of New York (New York, NY) Patent Number: 5,766,605 Date filed: April 15, 1994

182 Otitis Media

Abstract: There is disclosed according to the present invention a method for the control of autonomic nerve function in a mammal comprising administering a therapeutically effective amount of botulinum toxin to the mammal. Preferred embodiments include administering the toxin to control the function of an autonomic nerve which contributes to at least one symptom of rhinorrhea, otitis media, excessive salivation, asthma, COPD, excessive stomach acid secretion, spastic colitis or excessive sweating. Excerpt(s): The present invention is directed to the use of botulinum toxin to block parts of the autonomic nervous system for clinically beneficial effects. Botulinum toxin is produced by Clostridium botulinum in at least seven distinct serotypes, designated A-G (1). The toxin acts at cholinergic nerves to inhibit the release of acetylcholine, producing local chemical denervation. Because the seven types are antigenically distinct they have different anticholinergic potencies on cholinergic motor nerves (1). With respect to motor nerves, type A toxin has the greatest anticholinergic effect at the neuromuscular junction, followed by types E then B (2). Heretofore, botulinum toxin, i.e., botulinum toxin A, has been used to treat various motor nerve disorders. For example botulinum toxin injections are now considered treatment of choice for spasmodic dysphonia, blepharospasm, torticollis, focal hand dystonias and others (3). The use of type A toxin was approved in 1991 by the Food and Drug Administration as injectable therapy for strabismus and blepharospasm. Web site: http://www.delphion.com/details?pn=US05766605__ •

Treatment of otitis media by sublingual administration of DNA Inventor(s): Allen; Michael (Sacramento, CA), McMichael; John (Delanson, NY) Assignee(s): Milkhaus Laboratory (Delanson, NY) Patent Number: 5,948,768 Date filed: July 28, 1998 Abstract: Methods for treating symptoms of otitis media in a patient, are presented. Methods comprise administering an effective amount of DNA to a subject in a manner so as not to effect gene transfer. Excerpt(s): The present invention relates to methods for treatment of otitis media. The present invention relates generally to methods for treatment of pulmonary diseases and diseases associated with upper respiratory tract infection. Such diseases, including cystic fibrosis, emphysema, chronic bronchitis, sinusitis, and the common cold, have in common bronchial or sinus congestion, production of large amounts of sputum, and the possibility of secondary bacterial infection requiring antibiotic therapy. Acute otitis media is a bacterial or viral infection in the middle ear which is usually secondary to upper respiratory tract infections and is most common in children. Microorganisms may migrate from the nasopharynx to the middle ear over the surface of the eustachian tube's mucous membrane or by propagating in the lamina propria of the mucous membrane as a spreading cellulitis or thrombophlebitis. Pain and hearing loss are the most common presenting complaints although fever, nausea, vomiting and diarrhea may occur in young children. Therapy for acute otitis media includes analgesics, decongestants and antibiotics. In addition, topical vasoconstrictors may be administered into the nasal cavity to improve eustachian tube function. Further, systemic sympathomimetic amines such as ephedrine sulfate may also be administered. Web site: http://www.delphion.com/details?pn=US05948768__

Patents 183

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Use of indigestible oligosaccharides to reduce the incidence of otitis media in humans Inventor(s): Dohnalek; Margaret Ione Halpin (Worthington, OH), Hilty; Milo Duane (Lewis Center, OH), Ostrom; Karin Margaret (Reynoldsburg, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,849,324 Date filed: June 12, 1996 Abstract: A method is provided for reducing the incidence of otitis media in infants and young children by enterally administering indigestible fructooligosaccharides. More specifically, the present invention relates to a method for reducing the incidence of otitis media comprising administering to humans an indigestible fructooligosaccharide selected from the group consisting of 1-kestose, nystose and 1-.sup.F -B-fructofuranosyl nystose. The indigestible fructooligosaccharides can be produced through enzymatic synthesis, chemical techniques or isolated from plant materials and are administered in the form of a nutritional product, candy, tablets, chewing gums, lozenges, milk products, yogurts and the like. In a preferred embodiment of this invention, the fructooligosaccharides have a DP of 2 to 20 and still more preferably are the fructooligosaccharides FG.sub.2, GF.sub.3, and GF.sub.4. Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/001,000 filed Jul. 10, 1995. The present invention relates to a method for reducing the incidence of otitis media by enterally administering to humans an indigestible oligosaccharide. Prevention of otitis media in young children is a significant public health problem that has not been solved. Methods of prevention presently available are limited to practices that reduce transmission of infectious agents to susceptible individuals. Such methods include provision of clean water, hand washing, and good personal hygiene. The development of effective vaccines to prevent otitis media has been limited because of the large number of potential pathogens that can cause this disease and because young children, who are at greatest risk, often fail to develop effective immunity. Individuals treated with antibiotics for otitis media and other infectious diseases may become colonized with antibiotic-resistant bacteria and may not respond to antibiotic treatment. Web site: http://www.delphion.com/details?pn=US05849324__

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Use of phenylpropanolamine as a mucus secretogogue in the upper airways Inventor(s): Phipps; Roger J. (Sherburne, NY) Assignee(s): Norwich Eaton Pharmaceuticals, Inc. (Norwich, NY) Patent Number: 5,260,073 Date filed: June 4, 1992 Abstract: The present invention encompasses the novel method of using.+.phenylpropanolamine to induce mucous secretion in the upper airways of persons afflicted with sinusitis or otitis media characterized by retention of thickened respiratory secretions. These methods comprise administering to such person a safe and effective amount of.+-.phenylpropanolamine. It also encompasses certain novel oral compositions consisting essentially of l(-)-norephedrine and a pharmaceuticallyacceptable excipient base.

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Excerpt(s): This invention relates to (1) the novel method of using.+.phenylpropanolamine to induce mucous secretion in the upper airways of persons afflicted with sinusitis or otitis media characterized by retention of thickened mucus and respiratory secretions and (2) certain novel compositions of l(-)-norephedrine and a pharmaceutically acceptable excipient base. A substance that rotates plane-polarized light in a clockwise direction is said to be dextrorotatory and the rotation is said to be positive. A substance that rotates plane polarized light in a counterclockwise direction is said to be levorotatory and the rotation is said to be negative (Solomons, Organic Chemistry, p. 246 (1978)). The most active isomers physiologically for known uses are those with the S-configuration on the beta carbon atom (Lasagna, Phenylpropanolamine--A Review, p.28 (1980)). These are l (-)-norephedrine d(+)norpseudoephedrine. The d(+)-norpseudoephedrine isomer is a naturally occurring substance found primarily in the shrub Catha edulis and is used orally in Europe for its anorectic properties at a dose of about 40-50 mg/day. A racemic mixture of d(+)norephedrine and l(-)-norephedrine, generally referred to as either +phenylpropanolamine or phenylpropanolamine, is marketed as an anorectic at a dose of about 50-75 mg/day, and as a nasal decongestant at a dose of about 75-150 mg/day. Web site: http://www.delphion.com/details?pn=US05260073__ •

Use of surface active agent for the manufacture of a medicament for treatment of disorders of the middle ear Inventor(s): Hills; Brian Andrew (Queensland, AU), Woodcock; Derek Alan (Berkhampstead, GB) Assignee(s): Britannia Pharmaceuticals Limited (Surrey, GB) Patent Number: 6,395,295 Date filed: October 20, 2000 Abstract: The invention relates to the treatment of serous otitis media (glue ear). A medicament is disclosed which comprises a surface active phospholipid (SAPL) which is instilled as a powder into the middle ear. The SAPL has an affinity for the surface of the Eustachian tube and forms a film over its surface which prevents or deters reblockage of the tube. Excerpt(s): This invention relates to medicaments for use in the treatment of disorders of the middle ear. It is important to maintain the patency of the Eustachian tubes of the ear since failure to do so can lead to a number of clinical disorders. Blockage of the Eustachian tubes often occurs in persons experiencing discomfort arising from changes in ambient pressure, such as aviators and divers, and this can lead to pain and damage to the hearing. Partial or total blockage of the Eustachian tube can potentiate the onset of serous otitis media (more commonly known as glue ear), which is a very common disorder in children in the age range of about 7 to 12. This can cause partial deafness leading to lack of attention in school and developmental problems. Currently, the only available procedure for dealing with the problem of glue ear is to fit grommets or ventilation tubes, although antibiotics can offer short-term relief. Grommets are small plastic tubular inserts which require to be inserted by a surgical procedure involving an incision in the tympanic membrane. The procedure has disadvantages, quite apart from the need for a surgical procedure, including the risk of infection in the middle ear arising from direct contact with a contaminated environment and the requirement that the patient must avoid getting water in the treated ear, thus excluding the child from all aquatic activities. A further problem is that grommets tend to fall out.

Patents 185

Web site: http://www.delphion.com/details?pn=US06395295__ •

Use of xylitol and pharmaceutical compositions therefor Inventor(s): Kontiokari; Tero (Oulu, FI), Uhari; Matti (Oulu, FI) Assignee(s): Leiras Oy (Turku, FI) Patent Number: 6,066,677 Date filed: November 13, 1998 Abstract: A method of treating respiratory infections or complications derived therefrom in mammals, especially acute otitis media in humans, which includes administering to the mammal an effective amount of xylitol. The invention further concerns the use of xylitol for the preparation of a pharmaceutical composition for the treatment of respiratory infections or complications derived therefrom in mammals. One or more therapeutically active agents may optionally be added to the pharmaceutical composition, which can be a solid preparation, such as chewing gum, a powder or tablet, or a liquid preparation. Excerpt(s): The present invention relates to a means of treating respiratory infections or complications derived therefrom, in mammals, and more particularly, to a method of preventing acute otitis media in humans involving oral administration of xylitol. The invention further relates to the use of xylitol for the preparation of a pharmaceutical compositions for the treatment of respiratory infections or complications derived therefrom in mammals. The invention also concerns pharmaceutical compositions comprising xylitol. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference. Xylitol has been classified as a polyol or a sugar alcohol and is referred to as birch sugar, because it can be produced from birch. Xylitol occurs widely in nature, although the concentrations are low. Natural sources of xylitol include plums, strawberries, rasberries and rowan berries (1). Xylitol has the same relative sweetness as sucrose, and it has been used as a sugar substitute for dietary and medical purposes. Because of its five-carbon sugar alcohol structure, xylitol is unsuitable as a source of energy for most oral micro-organisms, such as Streptococcus mutans (2). Yet, most S. mutans strains are, via the fructose phosphotransferase system, able to transport xylitol into the cell, where it is phosphorylated into xylitol-5phosphate, which then has to be expelled from the cell (3). This metabolically futile xylitol cycle consumes energy stores of the call and is thought to be responsible for the inhibition of the growth of S. mutans observed both in vitro and in vivo when exposed to xylito (4). Web site: http://www.delphion.com/details?pn=US06066677__

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Vaccines for nontypable Haemophilus influenzae Inventor(s): Green; Bruce A. (Pittsford, NY), Zlotnick; Gary W. (Penfield, NY) Assignee(s): Praxis Biologics, Inc. (Rochester, NY) Patent Number: 5,601,831 Date filed: March 9, 1990

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Abstract: Protein "e" of H. influenzae, a lipoprotein of approximately 28,000 daltons, has been purified and sequenced. Protein "e" and peptides or proteins having a shared epitope, can be used to vaccinate against non-typable (and typable) H. influenzae and to prevent otitis media caused by H. influenzae. For this purpose, protein "e" or derivatives thereof can be produced in native, synthetic or recombinant forms and can be administered alone or in conjunction with other antigens of H. influenzae. Protein "e" can also be used in multivalent vaccines designed for H. influenzae and one or more other infectious organisms. Excerpt(s): Haemophilus influenzae are divided into two groups of strains, typable and nontypable. Strains which possess a known capsule are typed by the serological reaction of the capsule with reference antisera. Types a-f have been identified. Strains which fail to react with any of the reference antisera are nontypable. H. influenzae type b (Hib) is the most frequent cause of neonatal meningitis and other invasive infections in the United States (Fraser et al., 1974, Am. J. Epidemiol. 100:29-34). The major incidence of childhood meningitis occurs between the ages of one and five years. Sixty percent of the meningitis cases due to Hib occur in children under the age of two years (Fraser et al., supra). It is now well established that nontypable H. influenzae also cause diseases including pneumonia, bacteremia, meningitis, postpartum sepsis, and acute febrile tracheobronchitis in adults (Murphy et al., 1985, J. Infect. Diseases 152:1300-1307). In addition, nontypable H. influenzae are a frequent etiologic agent of otitis media in children and young adults. Indeed, about 20 to 40% of all cases of otitis media can be attributed to H. influenzae. Children may experience multiple infections of the same organism since infection confers no long lasting immunity. Currently, chronic or repeat otitis media is treated by administration of antibiotics and, if necessary, by drainage of the inner ear. H. influenzae strains have also been implicated as a primary cause of sinusitis (Cherry J. D. and J. P. Dudley, 1981, in Textbook of Pediatric Infectious Diseases, Feigin and Cherry eds., pp 103-105). Additionally, nontypable H. influenzae cause neonatal sepsis. Web site: http://www.delphion.com/details?pn=US05601831__ •

Xylitol delivery Inventor(s): Jones; Alonzo H. (P.O. Box 186, Hale Center, TX 79041) Assignee(s): none reported Patent Number: 6,054,143 Date filed: December 23, 1998 Abstract: Nasopharyngeal congestion, irritation, and inflammation and associated upper respiratory infections such as otitis media, sinusitis are adjunctivly treated and prevented by nasal application of xylitol/xylose in a saline solution. Excerpt(s): This invention relates to cleaning the nasopharynx and thereby reducing the number of bacteria resident there. This reduction translates into less problems with upper respiratory infections (specifically otitis and sinusitis) and reduction in the severity of asthma when the asthma is triggered by upper respiratory irritants. General practice physicians have ordinary skill in this art. Matti Uhari, one of Kontiokari's colleagues in Finland has been studying the effects of oral xylitol/xylose in reducing the incidence of recurrent otitis as disclosed in U.S. Pat. No. 5,719,196 (Uhari, 1996; Uhari, 1998). Uhari's original study looked at the effect of xylitol chewing gum in reducing the incidence of otitis. The highest incidence of otitis is in infants less than two who cannot

Patents 187

chew gum. Uhari subsequently studied the incidence of otitis in children getting an oral solution of xylitol. He found between a thirty and forty-percent reduction in the incidence of otitis using these supplements. The first level of response of the immune system is to try and wash out the irritated area. In upper respiratory infections this usually translates into nasal congestion because the immune system gets the fluid it needs for this washing by dilating blood vessels in the area. The traditional response to these symptoms is to turn off the immune response by a decongestant or antihistamine. A treatment much more respectful of the wisdom of the immune system is to facilitate it in the attempt to wash the irritated area. Web site: http://www.delphion.com/details?pn=US06054143__

Patent Applications on Otitis Media As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to otitis media: •

Certain dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency Inventor(s): Pendergast, William; (Durham, NC), Rideout, Janet L.; (Raleigh, NC), Siddiqi, Suhaib M.; (Raleigh, NC), Yerxa, Benjamin R.; (Raleigh, NC) Correspondence: Howrey Simon Arnold & White, Llp; Box 34; 301 Ravenswood AVE.; Menlo Park; CA; 94025; US Patent Application Number: 20020082417 Date filed: November 6, 2001 Abstract: The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y.sub.2 and/or P2Y.sub.4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment as well as facilitating sputum induction and expectoration. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/101,395, filed Jul.10, 1998, which was the National Stage of International Application No. PCT/US98/02702, filed Feb., 6, 1998, published Aug. 13, 1998 under PCT Article 21(2) in English; which claims the priority of U.S. application Ser. No. 08/798,508, filed Feb. 10, 1997, now U.S. Pat. No. 5,837,861, and U.S. application Ser. No. 08/797,472, filed Feb. 6, 1997, now U.S. Pat. No. 5,900,407. This invention relates to certain dinucleotides which increase the hydration of retained mucus secretions, stimulate the production of mucins and increase ciliary beat frequency to increase clearance of retained secretions. Chronic obstructive pulmonary disease (COPD) affects 15 million patients in the U.S. and is the sixth leading cause of death. It is characterized by the retention of mucus secretions in

10

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

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the lungs. Many patients diagnosed with COPD have a disorder called chronic bronchitis (CB), and 600,000 patients are hospitalized each year due to an acute exacerbation of CB. Cystic fibrosis and Primary Ciliary Dyskinesia (PCD) are other examples of lung disorders which assume a clinical profile similar to COPD. Ciliary dyskinesia, whether primary or secondary, results in retained secretions that can only be cleared by coughing. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition and method for treating the over-production of mucin in diseases such as otitis media using an inhibitor of MUC5AC Inventor(s): Basbaum, Carol; (San Francisco, CA), Kim, Young S.; (Hillsborough, CA), Li, Jian-Dong; (Glendale, CA), Lim, David; (Pasadena, CA), Shuto, Tsuyoshi; (Kumamoto, JP), Wang, Beinan; (Glendale, CA), Xu, Haidong; (Glendale, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 91614; US Patent Application Number: 20020151491 Date filed: November 27, 2001 Abstract: Disclosed herein is a method for the identification of a treatment for overproduction of mucin during otitis media (OM) and chronic obstructive pulmonary disease (COPD). The method uses a MUC5AC plasmid to identify novel cytoplasmic proteins of Nontypeable Haemophilus influenzae, a common mediator of OM and COPD, which up-regulate human MUC5AC mucin transcription via a positive p38 MAP kinase pathway and a negative PI 3-Kinase-Akt pathway. These proteins can be used to identify or design inhibitors of the p38 MAP kinase pathway and activators of the PI 3kinase Akt pathway. Excerpt(s): The present invention provides for methods of identifying compounds for treating medical conditions related to the inappropriate overproduction of mucin in the middle ear and respiratory system, as well as compounds and methods for treating such conditions. More specifically, the present invention identifies methods of treating mucin overproduction with P38 MAP kinase inhibitors or PI 3 kinase activators. The overproduction of mucin is associated with diseases such as Otitis media (OM), the most common childhood infection and also the leading cause of conductive hearing loss in children, and chronic obstructive pulmonary disease (COPD), a lower respiratory tract infection and the fourth leading cause of death in the United States. While it has been shown that overproduction of mucin, the major protein of mucus in the middle ear, plays an important role in the development of conductive hearing loss, little is known about the causes of and molecular mechanisms underlying mucin overproduction. Moreover, inappropriate antibiotic treatment of OM contributes to the worldwide emergence of multidrug-resistant strains of bacterial pathogens. Thus, due to the prevalence, long-term sequelae and the cost to our society, there is an urgent need for the development of novel therapeutic strategies. Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media (OM), the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined.

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

Composition and method for treatment of otitis media Inventor(s): Mautone, Alan J.; (Morristown, NJ) Correspondence: Richard L. Strauss, ESQ.; 2492 Oceanside Road; Oceanside; NY; 11572; US Patent Application Number: 20020064503 Date filed: December 4, 2001 Abstract: A process, composition and method for increasing and enhancing mammalian eustachian tube lumen patency and pressure equalization performance is disclosed wherein an aerosolized mixture of lipid crystals comprised of a mixture of one or more lipids surfactants and one or more spreading agents selected from the group consisting of sterols, lipids, fatty acids, cholesteryl esters, phospholipids, carbohydrates, and proteins, in powder form, and one or more propellants, in which the lipid surfactants and spreading agents are not soluble, are administered through a mammalian airway orifice. Upon administration, the propellant(s) are evaporated from the mixture and the lipid crystals are deposited within a subject mammalian eustachian tube whereupon said lipid crystals come into contact with lumen surfaces of the tube forming an amorphous spread film thereupon substantially decreasing the opening pressure of the lumen. In a second preferred embodiment, a therapeutically active agent effective in the treatment of otitis media is added to the mixture of lipid crystals and upon administration of said aerosol mixture, the amorphous spread film formed thereby carries said therapeutically active agent through the eustachian tube to the tissues of the middle ear. In an alternate preferred embodiment, the afore-mentioned reduction of surface tension and delivery of therapeutically active agents is provided by a mixture of lipid crystals comprised of surfactant(s), therapeutically active agents and a propellant in which such other components are not soluble. Excerpt(s): This application is a continuation-in-part of U.S. patent application No. 09/639,682 filed on Aug. 16, 2000, which said application is a continuation of U.S. patent application No. 09/450,884 filed Nov. 28, 1999 and issued as U.S. Pat. No. 6,156,294 on Dec. 5, 2001. The present invention relates to the field of pharmacological compositions and methods of utilizing such compositions in order to improve the flow of both naturally occurring fluids and pharmacologic agents through the mammalian eustachian tube. Otitis media is a pathological condition common to mammalian species and most common to children. During episodes of otitis media, fluid accumulates in the middle ear or, as it is also known, the tympanic cavity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Composition for inhibition of H. influenzae and treatment of otitis media and sore throat Inventor(s): Hwang, Shie-Ming; (Columbus, OH) Correspondence: Donald O. Nickey; 8765 Colvin Drive; Plain City; OH; 43064; US Patent Application Number: 20020106416 Date filed: January 30, 2002

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Abstract: The attachment of H. influenzae to human cells such as oropharyngeal cells, is inhibited by aqueous extracts of the plants known as Pogostemon cablin and Agastache rugosa. The composition obtained from the aqueous extraction of the plants Pogostemon cablin, Agastache rugosa or mixtures thereof is also effective in preventing or treating Otitis media and sore throat. The plant extract may be contained in a liquid enteral product such as an infant formula or may be incorporated into lozenges, candies, chewing gums and the like. The plant extract may also be administered as a throat spray or nasally using drops or a spray. A process for the production of a medicinal product is also disclosed. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/344,445 filed Feb. 13, 1998, now U.S. Pat. No. ______; which is a Divisional of U.S. patent application Ser. No. 08/761,321 filed Dec. 10, 1996, now U.S. Pat. No. 5,776,462. This invention relates to a composition for the inhibition of Haemophilus influenzae (hereinafter "H. Influenzae") attachment to human cells, more specifically the nasopharynx system, and thereby provide for the prevention and treatment of Otitis media and sore throat in humans. In this invention, a composition from an aqueous extract from the plant Pogostemon cablin or the plant Agastache rugosa has been isolated to treat and to effectively relieve humans from H. Influenzae infections, Otitis media and sore throat. The compositions have shown good anti-H. Influenzae activity in human trials and a neonatal rat model. H. Influenzae is a bacteria known to cause Otitis media and sore throat in humans. Modern medical science is constantly searching for new and more powerful agents to prevent, treat or retard bacterial and viral infections and cure the diseases they cause. Bacterial and viral infections of humans and domestic animals cost billions of dollars annually. Vast sums of money are spent each year by pharmaceutical companies to identify, characterize and produce new antibiotics and anti-virals to combat the emerging drug resistant strains which have become a serious problem. Reliable prophylactic treatments for disease prevention are also of major interest. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compounds and methods for treatment of asthma, allergy and inflammatory disorders Inventor(s): Cai, Xiong; (Belmont, MA), Chatelain, Pierre; (Woluwe Saint Pierre, BE), Differding, Edmond; (Louvain-La-Neuve, BE), Ellis, James; (Boxford, MA), Grewal, Gurmit; (Natick, MA), Hussoin, Sajjat; (Lexington, MA), Lassoie, Marie-Agnes; (BraineLe-Chateau, BE), Lewis, Timothy; (Marlborough, MA), Scannell, Ralph; (Hopkinson, MA), Toy-Palmer, Anna; (Arlington, MA), Young, Michelle; (Belmont, MA) Correspondence: Michael S. Greenfield; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030220347 Date filed: September 12, 2002 Abstract: The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted,4-alkylidenyl piperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferably asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria,

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pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/126,521, filed Mar. 26, 1999. The invention relates to the field of 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl piperidines. Leukotrienes are potent local mediators, playing a major role in inflammatory and allergic responses including arthritis, asthma, psoriasis, and thrombotic disease. Leukotrienes are straight chain eicosanoids produced by the oxidation of arachidonic acid by lipoxygenases. Arachidonic acid is oxidized by 5-lipoxygenase and ultimately converted to leukotrienes A4, B4, C4, D4 or E4. 15-Lipoxygenase is responsible for the conversion of arachidonic acid to various biologically active metabolites including 15hydroxy-5,8,11,13-ei- cosatetraenoic acid (15-HETE). Both of these mediators have been implicated in the pathogenesis of airway and allergic diseases such as asthma by contributing to bronchoconstriction, mucus secretion, and eosinophil migration. A mixture of one or more of such leukotrienes are known to be potent bronchoconstrictors. Thus, leukotrienes have been shown to play an important role in the pathology of asthma. Rigorous proof for the role of leukotrienes in asthma has been provided by several pivotal clinical trials in which orally administered 5-lipoxygenase (5-LO) inhibitors (or LTD4 receptor antagonists) produce clear therapeutic benefit in asthma patients. These benefits include reduction in the use of classic asthma therapies such as beta agonists and corticosteroids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHODS AND MATERIALS FOR INFLAMMATION OF MUCOSAL TISSUE

TREATING

AND

PREVENTING

Inventor(s): PONIKAU, JENS; (ROCHESTER, MN) Correspondence: Mark S Ellinger; Fish & Richardson; 60 South Sixth Street; Suite 3300; Minneapolis; MN; 55402 Patent Application Number: 20010002400 Date filed: October 22, 1998 Abstract: The invention involves methods and materials for treating and preventing non-invasive fungus-induced mucositis. Specifically, the invention involves administrating an antifungal agent such that it contact mucus in an amount, at a frequency, and for a duration effective to prevent, reduce, or eliminate non-invasive fungus-induced rhinosinusitis. This invention also provides methods and materials for diagnosing non-invasive fungus-induced rhinosinusitis and culturing non-invasive fungus from a mammalian mucus sample as well as specific antifungal formulations and medical devices for treating and preventing non-invasive fungus-induced rhinosinusitis. In addition, the invention provides methods and materials for treating and preventing other non-invasive fungus-induced mucositis conditions such as chronic otitis media, chronic colitis, and Crohn's disease. Further, the invention involves methods and materials for treating and preventing chronic asthma symptoms. Excerpt(s): This application claims priority from U.S. Provisional Application Serial No. 60/062,709, filed Oct. 22, 1997, U.S. Provisional Application Serial No. 60/063,414, filed Oct. 28, 1997, U.S. Provisional Application Serial No. 60/063,418, filed Oct. 28, 1997, U.S.

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Provisional Application Serial No. 60/083,272, filed Apr. 28, 1998 and U.S. Provisional Application Serial No. 60/086,397, filed May 22, 1998. The invention relates to methods and materials involved in the treatment and prevention of non-invasive fungus-induced inflammation of mucosal tissue as well as asthma symptoms. Mucositis, the inflammation of mucosal tissue, is a serious medical problem that affects millions of people worldwide. For example, conservative estimates indicate that between 20 to 40 million Americans suffer from chronic rhinosinusitis, an inflammation of the nasal cavity and/or paranasal sinuses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Synthetic chimeric fimbrin peptides Inventor(s): Bakaletz, Lauren O.; (Columbus, OH), Kaumaya, Pravin T.P.; (Westerville, OH) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20030113344 Date filed: August 19, 2002 Abstract: The present invention provides synthetic chimeric fimbrin peptides which induce an immunogenic response in animals to non-typable Haemophilus influenzae and that do not require tedious purification techniques. The synthetic chimeric fimbrin peptides reduce the severity of otitis media caused by Haemophilus influenzae. The synthetic chimeric fimbrin peptides are synthesized using commercially available peptide synthesizers. The synthetic chimeric fimbrin peptides comprises three peptide units. The first peptide unit is a subunit of the fimbrin protein. Preferably, the fimbrin subunit is comprised of the amino acids of Sequence ID No. 1 or Sequence ID No. 2. The second peptide unit is a t cell epitope, and preferably has the amino acid sequence of SEQ ID NO. 3. The third peptide unit is a linker peptide unit which joins the first and second peptide unit. The linking sequence preferably has from about 2 to about 15 amino acids, more preferably from about 2 to about 10 amino acids, most preferably from about 5 to about 6 amino acids. The synthetic chimeric fimbrin peptides are useful immunognes against NTHi and also useful as laboratory tool for detecting antibodies in sera. The invention also relates to an immunogenic composition conmtaining the synthetic chimeric fimbrin peptides and a pharmacologically acceptable carrier. Excerpt(s): Otitis media is an infection of the middle ear that occurs primarily in children. Left untreated, the disease can result in hearing loss and developmental delays. It is estimated that otitis media accounted for 31 million of the 130 million office visits for respiratory diseases in the period from 1977-87. Recent data indicate that suppurative and unspecified otitis media rank first in the list of the 30 most common diagnoses requiring a physician's office visit for patients up to age 24. Over one billion dollars per year is spent on treatment of this disease and the related loss of income for working parents is estimated to be between $300 and $600 million. Approximately 83% of all children will have had at least one episode of acute otitis media by three years of age. Non-typable strains of Haemophilus influenzae account for 25-30% of all cases of otitis media, 53% of recurrent otitis media, and are the primary pathogens isolated from 62% of cases of chronic otitis media with effusion. Although non-typable Haemophilus influenzae (NTHi) are primary pathogens in otitis media, neither the pathogenic mechanisms nor the host immunological response has been fully defined for this disease. Fimbriae, which are surface appendages found on non-typable Haemophilus

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influenzae, are produced by 100% of the bacteria recovered from the middle ears and nasopharyngeal region of children with chronic otitis media. A vaccine comprised of fimbrin, a filamentous protein derived from the fimbriae of non-typable Haemophilus influenzae was previously developed and is useful in studying, preventing, or reducing the severity of otitis media. However, existing methodologies to isolate fimbrin protein from the bacterial outer membrane are tedious and time-consuming. Similarly, purification of fimbrin expressed by the fimbrin gene in other host vector, is also tedious due to the homology between the fimbrin protein and the outer membrane proteins of the host vector. A strategy with other bacterial species has been to use an alternative immunogen having relatively short linear peptides. However, such alternative immunogens are of limited value due since antibodies to such alternative immunogens frequently fail to recognize the native pathogen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of symptoms of asthma and allergies Inventor(s): McMichael, John; (Delanson, NY) Correspondence: Marshall, Gerstein & Borun; 6300 Sears Tower; 233 South Wacker; Chicago; IL; 60606-6357; US Patent Application Number: 20020115632 Date filed: April 1, 2002 Abstract: Methods for treating symptoms of asthma, allergies and otitis media in a patient, are presented. Methods comprise administering an effective amount of DNA to a subject in a manner so as not to effect gene transfer. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/432,948 filed Nov. 3, 1999 which is a continuation-in-part of U.S. patent application Ser. No. 09/037,895 filed Mar. 10, 1998 which is a continuation-in-part of U.S. patent application Ser. No. 08/755,092 filed Nov. 22, 1996, issued Mar. 10, 1998 as U.S. Pat. No. 5,726,160 which is a continuation of U.S. patent application Ser. No. 08/421,232 filed Apr. 13, 1995. The present invention relates to methods for treatment of pulmonary disorders and otitis media. The present invention provides methods for treatment of pulmonary diseases. Such diseases, including cystic fibrosis, emphysema, chronic bronchitis, sinusitis, and the common cold, have in common bronchial or sinus congestion, production of large amounts of sputum, and the possibility of secondary bacterial infection requiring antibiotic therapy. The most serious of those diseases is cystic fibrosis, a genetic disorder of exocrine function characterized by abnormally viscous mucus secretions leading to chronic pulmonary obstruction, pancreatic insufficiency and elevated sweat sodium and chloride levels. Cystic fibrosis is often fatal. The viscosity of sputum produced by cystic fibrosis patients is thought to be due to its high content of DNA. Diseases such as bronchitis, emphysema, sinusitis, and the common cold are generally less severe than cystic fibrosis, but those diseases also may result in production of large amounts of sputum. Still other pulmonary diseases include mucositis (inflammation of the mucosal membranes) which is frequently associated with radiation therapy and which is characterized by production of a thick water deficient mucous which is difficult for the subject to eliminate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis Inventor(s): Andalibi, Ali; (Studio City, CA), Ganz, Tomas; (Los Angeles, CA), Lee, HaaYung; (La Crescenta, CA), Li, Jian-Dong; (Glendale, CA), Lim, David J.; (Pasadena, CA), Webster, Paul; (Pasadena, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020141986 Date filed: November 27, 2001 Abstract: Disclosed herein is a composition and a method for the treatment of otitis media and paranasal sinusitis using human defensins, lysozyme and/or lactoferrin as a new class of non-antibiotic antimicrobials. From studies of otitis media and paranasal sinusitis, it was observed that certain innate immune modulators were important in the bodies response to the infection. Therefore, these innate immune modulators, lysozyme, lactoferrin, and defensins were tested for use as a non-antibiotic treatment for infection, particularly infections such as otitis media and sinusitis. Excerpt(s): This application claims priority of the U.S. Provisional Application 60/253,492, filed Nov. 28, 2000, herein incorporated by reference in it entirety. The invention relates generally to the use of human beta defensins, lysozyme, and lactoferrin as a new class of non-antibiotic antimicrobials. More specifically, the invention relates to the use of these antimicrobials for the treatment of otitis media and paranasal sinusitis. The rapid worldwide increase in antibiotic resistance among pathogens has given rise to an urgent need to develop new and innovative non-antibiotic approaches to prevent and manage disease. Otitis media and sinusitis are two very common infections which are difficult to treat for a number of reasons, including antibiotic resistance. Otitis media (OM) is the most prevalent infectious disease affecting young children, and the major cause of conductive hearing loss among this group. OM is also the leading indication for antibiotic therapy. OM results in 31 million annual visits to physicians' offices and is estimated to have a yearly cost exceeding $5 billion. 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 otitis media, 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 “otitis media” (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 otitis media. You can also use this procedure to view pending patent applications concerning otitis media. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

195

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

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

Evidence Report/Technology Assessment: Number 15: Management of Acute Otitis Media Source: Agency for Healthcare Research and Quality. June 2000. Contact: Available from Agency for Healthcare Research and Quality. AHRQ Publications Clearinghouse. Voice (800) 358-9295. (AHRQ Publication No. 00-E009). Web site: http://www.ahcpr.gov. PRICE: no cost. Summary: The objective of this report was to analyze the evidence on the initial management of uncomplicated acute otitis media (AOM) in children. AOM is one of the most common diagnoses in children. Data from the National Ambulatory Medical Care Surveys (NAMCS), which did not differentiate between AOM and otitis media with effusion, indicated that the number of office visits for AOM increased more than twofold from 1975 to 1990. AOM was defined by the Technical Expert Panel as the presence of middle-ear effusion in conjunction with the rapid onset of one or more signs or

196 Otitis Media

symptoms of inflammation of the middle ear. Uncomplicated AOM was defined as AOM that is limited to the middle ear cleft. Bibliographical and other references. 49 tables. 21 figures. 5 evidence tables. 380pp. •

Otitis Media with Effusion: Clinical Practice Guidelines: Otitis Media with Effusion in Young Children Source: Silver Spring, MD: Agency for Health Care Policy and Research (AHCPR). 1994. 28 p. Contact: Available from AHCPR Publications Clearinghouse. P.O. Box 8457, Silver Spring, MD 20907. (800) 358-9295. PRICE: Single copy free. AHCPR Publication Number 94-0622. Summary: This guideline reflects the state of knowledge, current at the time of publication, on effective and appropriate care for otitis media with effusion in young children. The medical interventions considered in the Guideline include antibiotic therapy, steroid therapy, and antihistamine/decongestant therapy; the surgical interventions studied include myringotomy with insertion of tympanostomy tubes, adenoidectomy, and tonsillectomy. Short-term outcomes addressed are resolution of effusion and restoration of hearing; the long-term outcomes studied were the effects of otitis media with effusion on hearing and the hearing-related development of speech, language, and cognition. The editors note that because the prevalence of otitis media with effusion and the impact of associated hearing loss are greater among children with craniofacial or neurologic abnormalities, sensory deficits, or other medical illness, these children are excluded from Guideline recommendations. Recommendations are given for diagnosis and hearing evaluation; control of environmental factors; and sequencing of management interventions, including observation, use of antibiotics or other medications, and the appropriateness and timing of surgery. A glossary and brief subject index conclude the volume. 154 references.

•

Otitis Media in Young Children: Medical, Developmental, and Educational Considerations Source: Baltimore, MD: Paul H. Brookes Publishing Company. 1997. 351 p. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: brookespublishing.com. PRICE: $48.95 plus shipping and handling. ISBN: 1557662789. Summary: This text reviews national and international research on the effects of otitis media (middle ear infection) on young children's communication and learning. Applying that research to clinical practice, the authors also explain the best ways to identify, treat, and manage middle ear problems. Twelve chapters cover the definition and epidemiology of otitis media; diagnostic considerations; hearing loss in children with otitis media with effusion (OME); the effects of OME on auditory perception; phonological acquisition and otitis media; language development and otitis media; the impact of otitis media on cognitive, academic, and behavioral outcomes; family and professional partnerships in managing otitis media; the medical management of otitis media; the surgical management of OME; international perspectives on otitis media (including epidemiology and policy guidelines); and developmental outcomes in relation to early life otitis media. The text book concludes with an appendix that provides a clinical practice guidelines for managing OME; a subject index is also provided.

Books

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

Acute and Secretory Otitis Media; ISBN: 9062990231; http://www.amazon.com/exec/obidos/ASIN/9062990231/icongroupinterna

•

Advanced Therapy of Otitis Media by Charles D. Bluestone, Alper (2003); ISBN: 1550092014; http://www.amazon.com/exec/obidos/ASIN/1550092014/icongroupinterna

•

Clinical Problems in Otitis Media and Innovations in Surgical Otology by Michael M. Paparella, Marcos V. Goycoolea (Editor) (1982); ISBN: 0683067494; http://www.amazon.com/exec/obidos/ASIN/0683067494/icongroupinterna

•

Conquering Otitis Media by Charles D. Bluestone, et al; ISBN: 1896998054; http://www.amazon.com/exec/obidos/ASIN/1896998054/icongroupinterna

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Contemporary Diagnosis and Management of Otitis Media by Russell W. Steele, Dana L. Suskind-Liu; ISBN: 1884065457; http://www.amazon.com/exec/obidos/ASIN/1884065457/icongroupinterna

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Diagnosis and Management of Acute Otitis Media by Stan L. Block, Christopher J. Harrison; ISBN: 1884735649; http://www.amazon.com/exec/obidos/ASIN/1884735649/icongroupinterna

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Diseases Explained: Otitis Media Wall Chart by Lexi-Comp; ISBN: 193059819X; http://www.amazon.com/exec/obidos/ASIN/193059819X/icongroupinterna

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Ear infections facts for parents about otitis media (SuDoc HE 20.3652:EA 7) by U.S. Dept of Health and Human Services; ISBN: B000115YC2; http://www.amazon.com/exec/obidos/ASIN/B000115YC2/icongroupinterna

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Evidence-Based Otitis Media (Book With CD-ROM For Windows & Macintosh) by Richard M. Rosenfeld, Charles D. Bluestone; ISBN: 1550090836; http://www.amazon.com/exec/obidos/ASIN/1550090836/icongroupinterna

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Language Learning and Otitis Media by M. Suzanne Hasenstab; ISBN: 0316349984; http://www.amazon.com/exec/obidos/ASIN/0316349984/icongroupinterna

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Language Learning and Otitis Media; ISBN: 0890793247; http://www.amazon.com/exec/obidos/ASIN/0890793247/icongroupinterna

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Office visits for otitis media : United States, 1975-90 (SuDoc HE 20.6209/3:214) by Susan M. Schappert; ISBN: B00010CO6M; http://www.amazon.com/exec/obidos/ASIN/B00010CO6M/icongroupinterna

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Otitis media : facts for parents (SuDoc HE 20.3652:OT 4) by U.S. Dept of Health and Human Services; ISBN: B000113X20; http://www.amazon.com/exec/obidos/ASIN/B000113X20/icongroupinterna

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Otitis Media and Child Development (Communicating by Language, Vol 10) by James F. Kavanagh (Editor); ISBN: 0912752122; http://www.amazon.com/exec/obidos/ASIN/0912752122/icongroupinterna

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Otitis Media and Sinusitis by Russell W. Steele; ISBN: 1581110383; http://www.amazon.com/exec/obidos/ASIN/1581110383/icongroupinterna

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Otitis Media Coping With the Effects in the Classroom by D. Davis; ISBN: 0962232602; http://www.amazon.com/exec/obidos/ASIN/0962232602/icongroupinterna

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Otitis Media Effusion in Children by David Chalmers (Author); ISBN: 0901260770; http://www.amazon.com/exec/obidos/ASIN/0901260770/icongroupinterna

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Otitis Media En Lactantes y Ninos by Charles D. Blustone, Jerome O. Klein (2000); ISBN: 9500602261; http://www.amazon.com/exec/obidos/ASIN/9500602261/icongroupinterna

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Otitis Media in Children: A Controversial Issue by Jean-Philippe Guyot (Editor) (1999); ISBN: 3805568355; http://www.amazon.com/exec/obidos/ASIN/3805568355/icongroupinterna

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Otitis media in early childhood and its relationship to later speech and language (SuDoc ED 1.310/2:312801) by U.S. Dept of Education; ISBN: B00010FLQM; http://www.amazon.com/exec/obidos/ASIN/B00010FLQM/icongroupinterna

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Otitis Media in Infants and Children by Charles D., M.D. Bluestone, et al (2001); ISBN: 0721687091; http://www.amazon.com/exec/obidos/ASIN/0721687091/icongroupinterna

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Otitis Media in Infants and Children (1995); ISBN: 072161759X; http://www.amazon.com/exec/obidos/ASIN/072161759X/icongroupinterna

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Otitis Media in Young Children: Medical, Developmental, and Educational Perspectives by Joanne E.Wick Roberts (Editor), et al (1997); ISBN: 1557662789; http://www.amazon.com/exec/obidos/ASIN/1557662789/icongroupinterna

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Otitis Media Today by M. Tos (Editor), et al; ISBN: 9062991653; http://www.amazon.com/exec/obidos/ASIN/9062991653/icongroupinterna

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Otitis Media with Effusion in Children by David Chalmers (Author), et al (1991); ISBN: 0521412242; http://www.amazon.com/exec/obidos/ASIN/0521412242/icongroupinterna

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Otitis Media With Effusion in Children (1991); ISBN: 0632024674; http://www.amazon.com/exec/obidos/ASIN/0632024674/icongroupinterna

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Otitis media with effusion in children (SuDoc HE 20.6520/4:12) by U.S. Dept of Health and Human Services; ISBN: B00010Q0OE; http://www.amazon.com/exec/obidos/ASIN/B00010Q0OE/icongroupinterna

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Otitis Media With Effusion in Young Children: Clinical Practice Guideline No 12 by S/N 017-026-00116-6, Sylvan E. Stool (1994); ISBN: 9995523213; http://www.amazon.com/exec/obidos/ASIN/9995523213/icongroupinterna

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Otitis media; proceedings; ISBN: 0398022941; http://www.amazon.com/exec/obidos/ASIN/0398022941/icongroupinterna

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Recent Advances in Otitis Media by Goro Mogi, et al; ISBN: 9062991017; http://www.amazon.com/exec/obidos/ASIN/9062991017/icongroupinterna

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Recent Advances in Otitis Media: Proceedings by David J. Lim, Charles D. Bluestone; ISBN: 1556640870; http://www.amazon.com/exec/obidos/ASIN/1556640870/icongroupinterna

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Recent Advances in Otitis Media: Proceedings of the Seventh International Symposium (CD-ROM) by Bluestone, et al; ISBN: 1550091034; http://www.amazon.com/exec/obidos/ASIN/1550091034/icongroupinterna

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Recent Advances in Otitis Media: Proceedings of the Sixth International Symposium by David J. Lim, et al; ISBN: 1550090283; http://www.amazon.com/exec/obidos/ASIN/1550090283/icongroupinterna

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Screening Children's Hearing: A Review of the Literature and Implications of Otitis Media by Mark Haggard, Eamonn Hughes; ISBN: 0113212100; http://www.amazon.com/exec/obidos/ASIN/0113212100/icongroupinterna

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Screening For Hearing Loss and Otitis Media In Children by Jackson Roush (Editor); ISBN: 0769300006; http://www.amazon.com/exec/obidos/ASIN/0769300006/icongroupinterna

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Targeted Therapies in Otitis Media and Otitis Externa by Charles D., MD Bluestone, et al (2003); ISBN: 1550092553; http://www.amazon.com/exec/obidos/ASIN/1550092553/icongroupinterna

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The Relationship Between Inflammation and Structural Changes in the Airways of the Lower and Upper Respiratory Tract: Studies in Patients With Asthma, Sjogren's Syndrome, Rhinitis and Children With Otitis Media With Effusion (Comprehensive Summaries of Uppsala Dissertations, 932) by Kawa Amin (2000); ISBN: 9155447279; http://www.amazon.com/exec/obidos/ASIN/9155447279/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “otitis media” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Acute otitis media. Author: Mollison, William Mayhew.; Year: 1943; London, Bale; Danielsson, 1932

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Aero-otitis media and aerosinusitis; experimental histo-pathological changes due to oxygen deficiency and oxygen poisoning. Author: Aschan, Gunnar Knutsson,; Year: 1951; Uppsala [Almqvist; Wiksell] 1948

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Bacteriological studies on exudative otitis media occurring in six communities of Alaskan natives [by] Karl R. Reinhard [et al.]. Author: Reinhard, Karl R.; Year: 1953; Uppsala, 1970

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Chronic secretory otitis media in children; a clinical study. Author: Kokko, Eino.; Year: 1948; Oulu [Distributed by the Almqvist; Wiksell Periodical Co., Stockholm] 1974

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Clinico-bacteriologic studies on acute otitis media; aspiration of the tympanum as a diagnostic and therapeutic method. Author: Lahikainen, E. A.; Year: 1967; Turku, 1953

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Experimental obstruction of the eustachian tube: a contribution to knowledge of the pathogenesis of secretory otitis media Author: Beek, Johan Marinus Herman van der,; Year: 1969; Heerlen [Netherlands]: Schrijen-Lippertz BV Voerendaal, 1981

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Experimental production of serous otitis media in dogs. Author: Reiner, Carl Ernest,; Year: 1969; [Minneapolis] 1969

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Middle ear fluid in acute otitis media; amount, total protein content and protein composition, relation between protein composition of serum and fluid. [Tr. from the Finnish. Author: Vuori, Martti.; Year: 1952; Turku, 1959]

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Occurrence of acute otitis media Author: Pukander, Juhani.; Year: 1974; Tampere, Finland: Tampereen Yliopisto, University of Tampere, 1982; ISBN: 9514412680

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Otitis media and child development: speech, language, and education Author: Hanson, David G.,; Year: 1969; St. Louis, Mo.: Annals Pub. Co., 1979

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Otitis media: diagnosis, therapy, and prevention and control; 348 reference: 1964-1970; period of search: 1967-Aug., 1970. Author: Information Center for Hearing, Speech, and Disorders of Human Communication.; Year: 1959; Baltimore, 1971

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Recent advances in otitis media with effusion: proceedings of the second international symposium, May 9-11, 1979, Columbus, Ohio Author: Senturia, Ben Harlan,; Year: 1944; St. Louis: Annals Pub. Co., 1980

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Secretory otitis media and its sequelae Author: Sadé, Jacob.; Year: 1969; New York: Churchill Livingstone, 1979; ISBN: 0443080283 http://www.amazon.com/exec/obidos/ASIN/0443080283/icongroupinterna

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Tissue penetration of erythromycin in Waldeyer's ring; and, Bacteriology of secretory otitis media Author: Sundberg, L.; Year: 1971; Karlskrona, Sweden: [s.n.]; Stockholm, Sweden: Distributed by the Almqvist; Wiksell Periodical Co., 1981

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

Complications of Chronic Otitis Media Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 433-445.

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Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: Chronic otitis media (COM) is a common otologic (ear) condition characterized by a condition of chronic infection and otorrhea (drainage from the ear) through a tympanic membrane (eardrum) perforation. This chapter on the complications of COM is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. In this chapter, the author discusses extracranial and extratemporal complications of COM, intratemporal complications, and intracranial complications of the disease. The author notes that host-related factors, such as impaired resistance to disease or unfavorable anatomy, and microbiologic factors, such as bacterial invasiveness or degree of antimicrobial resistance, are intertwined in the pathophysiology of complications of COM. 7 figures. 64 references. •

Chronic Otitis Media and Cholesteatoma Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 409-431. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: Chronic otitis media (COM) is an unresolved inflammatory process of the middle ear and mastoid. The disease nearly always is associated with tympanic membrane (eardrum) perforation and may be active when infection and otorrhea (drainage from the ear) are present or quiet when they are absent. Cholesteatoma is a tumor like lesion of the temporal bone, causing an ingrowth of skin which invades the middle ear and the mastoid spaces. This chapter on COM and cholesteatoma is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. In the section on COM, the authors discuss definition, etiology, bacteriology, pathology, sensorineural hearing loss, history and physical findings, audiologic examination, vestibular examination, radiographic evaluation, medical treatment, tuberculous otomastoiditis, nontuberculous mycobacteria and COM, and Wegener's granulomatosis. In the section on cholesteatoma, the authors cover definition, pathology and pathogenesis of acquired cholesteatoma, growth patterns of cholesteatoma, epitympanic cholesteatomas, posterior mesotympanic cholesteatomas, history and physical findings of acquired cholesteatoma, audiologic examination, radiographic evaluation, the medical management of cholesteatomas, cholesteatomas in children, and congenital cholesteatoma. T39 figures. 123 references.

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Otitis Media with Effusion Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 383-396. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X.

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Summary: Otitis media with effusion (OME) is an inflammatory condition of the middle ear and mastoid air cell system characterized by accumulation of fluid in the middle ear without signs or symptoms of acute infection. This chapter on OME is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. This chapter covers pathogenesis; the anatomy and function of the Eustachian tube; epidemiology; diagnosis; treatment options, including medical or surgical, and complications of treatment; adenoids; cleft palate; related nasal conditions; complications of OME in the balance mechanisms or the middle ear structure; high negative pressure; OME in adults; and barotrauma. 7 figures. 81 references. •

Sorting It Out: Educational Affects From Early Chronic Otitis Media, CAPD, ADD or LD? Source: in Johnson, C.D., ed. Educational Audiology Monograph. Tampa, FL: Educational Audiology Association. 1996. p. 6-11. Contact: Available from Educational Audiology Association. 4319 Ehrlich Road, Tampa, FL 33624. (800) 460-7322; Fax (813) 968-3597. PRICE: $10.00 plus shipping and handling. Summary: There are numerous behavior and learning characteristics that can be considered typical of students with learning disabilities, attention deficit disorders (ADD), central auditory processing disorders (CAPD), and those who have had a history of chronic otitis media. This paper focuses on the similarities between these disabling conditions and suggests investigational methods with which educational audiologists can begin to differentiate between the populations. The authors begin by defining terms, then discuss the etiology of learning problems, the need for a multidisciplinary team to participate in each child's education planning, overlapping incidence, general classroom function, considering otitis media history in relation to language ability, determining current hearing status, assessing the child's ability to process auditory information in both quiet and noise, auditory processing and memory, and attention. 4 tables. 33 references.

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Relationship of Otitis Media to Speech Processing and Language Development Source: in Katz, J.; Stecker, N.; Henderson, D. Central Auditory Processing: A Transdisciplinary View. St. Louis, MO: Mosby-Year Book, Inc. 1992. p. 187-197. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, P.O. Box 46908, St. Louis, MO 63146. (800) 426-4545; Fax (800) 535-9935; E-mail: [email protected].; http://www.mosby.com. PRICE: $43.95 plus shipping and handling. ISBN: 1556643721. Summary: This book chapter focuses on the relationship between fluctuating peripheral hearing loss caused by persistent otitis media (middle ear infection) and the development of speech processing. The author briefly reviews some of the research results that led to the current controversy over the role of frequent ear infections in the development of speech and language in children. The author concludes that, while the hearing loss associated with otitis media can be measured consistently, the related language effects cannot be so quantified. Otitis media appears to lead to differences in language development of different kinds during different periods of development. A consistent finding is that otitis media leads to across the board delays in language development between two and three years of age. Not enough children with early persistent otitis media suffer sufficient language delay for statistical significance. Those

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who do suffer delay may do so for a number of environmental reasons as well as otitis media. The author notes that the developmental language difficulties related to otitis media may be more complicated than present language evaluation can elucidate. 1 figure. 4 tables. 22 references. (AA-M). •

Epidemiology, Natural History, and Management of Otitis Media Source: in Bess, F.H. Children with Hearing Impairment: Contemporary Trends. Nashville, TN: Vanderbilt Bill Wilkerson Center Press. 1998. p. 191-206. Contact: Available from Vanderbilt Bill Wilkerson Center Press. 1114 19th Avenue, South, Nashville, TN 37212-2197. (877) 844-3840 or (615) 936-5023. Fax (615) 936-5013. PRICE: $60.00 plus shipping and handling. ISBN: 0963143980. Summary: This chapter from a section on otitis media is from a book of papers presented at the Fourth International Symposium on Childhood Deafness (Kiawah Island, South Carolina, 1996). This chapter considers the epidemiology, natural history, and management of otitis media. The author provides communicative disorders specialists with an evidence based approach to managing otitis media. Rational management begins by understanding the natural history of untreated otitis media and knowing what to expect from medical therapy. Next, a stepwise treatment plan is presented, based on epidemiologic studies, systematic reviews of clinical trials, and personal experience of a pediatric otolaryngologist who has successfully treated thousands of children with otitis media. The author emphasizes the broad and fundamental principles underlying treatment, not on the specifics of antibiotic selection or surgical therapy. The author concludes that realistic expectations on the part of all involved parties should facilitate rational decisions about watchful waiting, medical therapy, and the need for surgical intervention. 7 tables. 79 references.

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Acute Suppurative Otitis Media and Mastoiditis Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 397-408. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: This chapter is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. This chapter focuses on the clinical and pathologic features of acute bacterial infections of the middle ear cleft (acute otitis media) and mastoid process. In the first section, on acute otitis media, the authors discuss a definition, epidemiology, etiology, bacteriology, pathology, symptoms, physical findings, laboratory tests, hearing tests, clinical course, medical treatment, surgery (myringotomy, i.e., drainage tubes), follow up care, and complications. In the section on acute mastoiditis, the authors discuss a definition, incidence, bacteriology, pathology, symptoms, physical findings, laboratory tests, auditory tests, radiographic evaluation, medical management, and surgical management. The authors also discuss acute bullous myringitis (which involves the lateral middle ear boundary), the technique of simple mastoidectomy, and temporal bone fungal infection. 13 figures. 33 references.

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Hearing Loss Among Children with Otitis Media with Effusion Source: in Roberts, J.E.; Wallace, I.F.; Henderson, F.W. Otitis Media in Young Children: Medical, Developmental, and Educational Considerations. Baltimore, MD: Paul H. Brookes Publishing Company. 1997. p. 63-92. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. PRICE: $48.95 plus shipping and handling. ISBN: 1557662789. Summary: This chapter on hearing loss among children with otitis media with effusion (OME) is from a textbook on the medical, developmental, and educational impact of otitis media on young children. The authors examine the effect of OME on peripheral hearing in the context of current definitions of hearing loss in children. The authors review the use of various audiologic tests useful in the identification and assessment of infants and children with middle ear pathology. Next, they consider the influence of hearing loss associated with OME on speech perception and auditory processing, first by examining background theory and then by reviewing several current investigations that support a relationship between early conductive hearing impairment and higher order auditory deficits. Finally, the chapter concludes with suggested approaches to the management of children with conductive hearing loss at home and in the classroom. 6 figures. 86 references. (AA-M).

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Otitis Media and Associated Complications Source: in Jafek, B.W.; Stark, A.K., eds. ENT Secrets: Questions You Will Be Asked On Rounds, In the Clinic, In the OR, On Exams. Philadelphia, PA: Hanley and Belfus. 1996. p. 39-43. Contact: Available from Hanley and Belfus. Medical Publishers, 210 South 13th Street, Philadelphia, PA 19107. (800) 962-1892 or (215) 546-7293; Fax (215) 790-9330; http://www.hanleyandbelfus.com. PRICE: $35.95 plus shipping and handling. ISBN: 1560531592. Summary: This chapter on otitis media and associated complications is from a book that utilizes a question and answer format to review details of the specialty of otorhinolaryngology (ear, nose and throat, or ENT). Topics covered include the terminology used to describe ear infections, the functions of the eustachian tube, the organisms most commonly found in otitis media, the organisms found in mastoiditis, the diagnosis of otitis media is diagnosed, the indications for tympanometry in the diagnosis of otitis media, hearing loss related to otitis media with effusion (OME), the problems of otitis media recurring in younger children, the medical management of acute otitis media, the medical management of chronic OME, the environmental risk factors for OME, tympanocentesis, myringotomy, the surgical options for treating otitis media, the patient selection considerations for surgery, the complications of tympanostomy tube insertion, the indications for adenoidectomy, the intratemporal complications of untreated otitis media, the intracranial complications of untreated otitis media, the significance of unilateral otitis media in an adult, and the use of steroid therapy in the treatment of OME. 8 references.

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Phonological Acquisition and Otitis Media: Speech Perception and Speech Production Source: in Roberts, J.E.; Wallace, I.F.; Henderson, F.W. Otitis Media in Young Children: Medical, Developmental, and Educational Considerations. Baltimore, MD: Paul H. Brookes Publishing Company. 1997. p. 109-131. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. PRICE: $48.95 plus shipping and handling. ISBN: 1557662789. Summary: This chapter on phonological acquisition and otitis media is from a textbook on the medical, developmental, and educational impact of otitis media on young children. Phonology is the component of language that underlies speech perception and production. The components of phonology are features, segments (consonants and vowels), syllables, words, phrases, and a small set of rules or constraints that govern the form of these components as well as the relationships among them. The authors focus on the development of speech perception and production in children with and without histories of otitis media with effusion (OME). The authors examine the effects of limitations in perception on the acquisition of phonology and morphology. They first review theories of phonological acquisition, then discuss studies of speech acquisition in children with OME. The authors advocate early intervention, using language stimulation techniques for children who, by 1 year of age, have a significant history of OME. This can take the form of parent training to provide an enriched language environment. They also stress that careful consideration should be given to the fluctuating hearing losses exhibited by young children with a history of OME. 3 figures. 65 references. (AA-M).

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Effects of Otitis Media with Effusion on Auditory Perception Source: in Roberts, J.E.; Wallace, I.F.; Henderson, F.W. Otitis Media in Young Children: Medical, Developmental, and Educational Considerations. Baltimore, MD: Paul H. Brookes Publishing Company. 1997. p. 93-108. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. PRICE: $48.95 plus shipping and handling. ISBN: 1557662789. Summary: This chapter on the effects of otitis media with effusion (OME) on auditory perception in children is from a textbook on the medical, developmental, and educational impact of otitis media on young children. The authors note that, in children with a history of chronic OME, audiometric detection thresholds typically return to normal soon after the restoration of adequate middle ear ventilation. However, deficits in more complex auditory processing may persist long after the audiogram has returned to normal limits. The authors review the effect of chronic OME on the development of some basic auditory abilities and consider the ramifications that the psychoacoustic data may have for hearing in real-world environments. Topics include typical auditory development, the theoretical consequences of conductive hearing loss, binaural and monaural hearing, and directions for future research. 3 figures. 50 references. (AA-M).

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Medical Management of Otitis Media Source: in Roberts, J.E.; Wallace, I.F.; Henderson, F.W. Otitis Media in Young Children: Medical, Developmental, and Educational Considerations. Baltimore, MD: Paul H. Brookes Publishing Company. 1997. p. 219-243. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. PRICE: $48.95 plus shipping and handling. ISBN: 1557662789. Summary: This chapter on the medical management of otitis media is from a textbook on the medical, developmental, and educational impact of otitis media on young children. The author notes that the most frequent therapeutic decision a primary care physician evaluating preschool children must make concerns the selection of an antibiotic treatment program for patients with a clinical diagnosis of acute otitis media (AOM). The antibiotic selection process is becoming more complex as common otitis pathogens demonstrate, with increasing frequency, either high level resistance or significantly reduced susceptibility to commonly employed antibiotics. This chapter includes a review of the microbiology and pathogenesis of otitis media, a discussion of the microbiologic and pharmacologic data upon which antibiotic treatment decisions should be based, and a summary of the evidence for the efficacy of antibiotics in bacterial otitis media. In addition, the authors provide an examination of the microbiology of AOM in children with persisting symptoms after antibiotic treatment, a discussion of an approach to the child with treatment resistant otitis in the era of antibiotic-resistant pneumococci, a survey of options for management recurrent suppurative AOM, and a review of the roles of antibiotics and corticosteroids in the management of persistent nonsuppurative otitis media with effusion (OME). 13 tables. 57 references. (AA-M).

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Surgical Management of Otitis Media with Effusion Source: in Roberts, J.E.; Wallace, I.F.; Henderson, F.W. Otitis Media in Young Children: Medical, Developmental, and Educational Considerations. Baltimore, MD: Paul H. Brookes Publishing Company. 1997. p. 245-264. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. PRICE: $48.95 plus shipping and handling. ISBN: 1557662789. Summary: This chapter on the surgical management of otitis media with effusion (OME) is from a textbook on the medical, developmental, and educational impact of otitis media on young children. The authors note that the surgical treatment of middle ear effusion is the most frequent reason for administering general anesthesia to children in the United States. This chapter discusses the various procedures currently used for the surgical treatment of middle ear fluid. First, middle ear anatomy and physiology are discussed. Next, the different surgical procedures for treatment of OME are described, followed by a review of the effectiveness of these procedures. Procedures covered include tympanocentesis (needle aspiration of the middle ear space), myringotomy, myringotomy with tympanostomy tube insertion, exploratory tympanotomy, middle ear reconstruction, mastoidectomy, and adenoidectomy and tonsillectomy. 7 figures. 2 tables. 29 references. (AA-M).

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Middle-Ear Disease (Otitis Media) Source: in Blackman, J.A. Medical Aspects of Developmental Disabilities in Children, Birth to Three. Frederick, MD: Aspen Publishers, Inc. 1997. p. 189-193. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21704. (800) 638-8437; Fax (301) 417-7650. PRICE: $40.00 plus shipping and handling. ISBN: 0834207591. Summary: This chapter, from a early childhood textbook on the medical aspects of developmental disabilities in young children (birth to age three), outlines concerns related to middle ear disease (otitis media). Otitis media is an inflammatory disease of the middle ear, common in children under six years of age. The author defines two types of otitis media: acute otitis media, characterized by a red, bulging, immobile eardrum, ear pain, and bacteria and pus in the middle ear; and serous otitis media (or otitis media with effusion, OME), a more chronic condition that includes fluid in the middle ear space, which can result in varying degrees of hearing loss. Topics covered include incidence, etiology (cause), detection, course, accompanying health problems, medical management, and implications for early intervention. The most prudent course at the present time is to treat acute infections with appropriate antibiotics, to follow the status of the middle ear with pneumatic otoscopy or impedance tympanometry, and to consider various treatments for recurrent acute infections and persistent serous fluid in the middle ear. The author concludes that, because of the age group served and the types of disabilities encountered, ear infections are common in children participating in early education and therapeutic programs. Teachers and therapists must understand the nature of otitis media and appreciate its impact on health and developmental function.

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Epidemiology and Natural History of Otitis Media Source: in Bess, F. and Hall, J.W., III., eds. Screening Children for Auditory Function. Nashville, TN: Bill Wilkerson Center Press. 1992. p. 31-37. Contact: Available from Bill Wilkerson Center Press. 1114 19th Avenue South, Nashville, TN 37212. (615) 936-5023. Fax (615) 936-5013. PRICE: $20.00 plus shipping and handling. ISBN: 0963143905. Summary: This chapter, from a textbook on screening children for auditory function, discusses the epidemiology and natural history of otitis media. Topics covered include the incidence of acute otitis media (AOM); risk factors associated with AOM, including age, sibling history, gender, breastfeeding, age at first episode, and day care; persistent middle ear effusion (MEE); the natural history of otitis media and hearing loss; suppurative complications of otitis media; and nonsuppurative complications of otitis media. The author notes that the results from recent studies suggest that children with recurrent AOM and prolonged time spent with middle ear effusion have lower scores on tests of cognitive abilities, speech and language, and school performance. 7 references.

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

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

Ear Infections: Too Serious to Ignore Source: Princeton, NJ: Films for the Humanities and Sciences. 1996. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400; Fax (609) 275-3767; E-mail: [email protected]; http://www.films.com. PRICE: $99.00 plus shipping and handling. Stock Number BFA6425. Summary: By the age of three, about two thirds of children will be diagnosed with otitis media (infection of the middle ear). Middle ear infections are one of the most common childhood diseases and their frequency is on the rise. This program, narrated by Dr. Jerome Klein, professor of pediatrics at Boston University School of Medicine, explains why the prevalence of middle ear infections is increasing, and provides specific advice about what can be done to prevent children from being infected. The program has five sections: the risk factors for otitis media, particularly those environmental factors (like smoking, and child care options) that can be controlled; anticipated clinical course,

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including symptoms, diagnosis, and treatment issues; use of antimicrobial agents (antibiotics); middle ear effusion and accompanying problems with hearing loss; and prevention strategies, including vaccination, chemotherapy (antibiotic prophylaxis), and health education. •

SOM: A Silent Disease Source: Chicago, IL: Craniofacial Center, University of Illinois at Chicago. 199X. (videocassette). Contact: Available from Craniofacial Center. MC 588, University of Illinois at Chicago, 808 South Wood Street, Room 476, Chicago, IL 60612-7308. (312) 996-0178. PRICE: $95.00 plus shipping and handling; $30.00 for 10-day rental, applicable toward purchase. Summary: This videotape program explains the problem of silent otitis media (SOM), focusing particularly on why children with cleft palate are susceptible to ear disease. The program also emphasizes prevention and correction of SOM in its early stages. A description of myringotomy (PE tubes) surgery is provided. The videotape is designed for parents, patients, and all health professionals who deal with cleft lip/palate. English and Spanish versions of the program are provided on the same videotape. (AA-M).

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Central Auditory Processing Disorders Source: Low Moor, VA: American Guild of Central Auditory Processing Disorders. 1997. (videocassette). Contact: Available from Educational Audiology Association. 4319 Ehrlich Road, Tampa, FL 33624. (800) 460-7322. Fax (813) 968-3597. E-mail: [email protected]. PRICE: $20.00 plus $3.00 shipping and handling per copy. Summary: This videotape program teaches parents about central auditory processing disorders (CAPD) in children. The narrator stresses the importance of increasing awareness of CAPD in order to help these children as early in life as possible. The program discusses the role of the brain in processing auditory input and defines CAPD. Other topics include the role of speech language therapy, the use of compensatory strategies in the classroom and home environments, the causes of CAPD (notably otitis media), common symptoms of CAPD, diagnostic strategies, the use of enhancement of the auditory environment, the role of the speech language pathologists, and strategies for teaching children with CAPD. Symptoms discussed include difficulty with listening, distraction, difficulty learning with phonics, poor learning through auditory channels, and behavioral problems. The program concludes by reviewing these symptoms and encouraging parents to intervene as soon as they notice any of the symptoms in their child. The contact information for the American Guild of Central Auditory Processing Disorders is included.

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Managing Earaches in Children Source: Timonium, MD: Milner-Fenwick. 199x. (videocassette). Contact: Available from Milner-Fenwick, 2125 Greenspring Drive, Timonium, MD 21093. (800) 432-8433. PRICE: $125.00. Number CC-12. Summary: This videotape, designed for parents, describes common causes, symptoms, complications, treatment, and coping tips for ear infections in children. The program begins by briefly describing how the ear works and illustrating the structure of the inner ear. Temporary measures are suggested to relieve pain until a doctor can be consulted.

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Treatments discussed include antibiotics; antihistamines or decongestants; saline nasal sprays; and, for chronic infection, potential surgical treatment such as surgery to release fluid, insertion of tubes, and removal of the adenoids. Potential complications of ear infection are described, including ruptured eardrum, mastoiditis, and chronic serous otitis media. Parents are strongly urged to consult a physician any time a child experiences symptoms such as earache, clogged ears, discharge, dizziness, irritability, ear pulling, fever, or loss of hearing. The video concludes with some suggestions to help prevent infection, including avoiding exposure to colds and other infections, keeping children away from cigarette smoke, and never bottle feeding a child while the child is lying down.

Bibliography: Multimedia on Otitis Media The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in otitis media (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on otitis media: •

Chronic otitis media [videorecording]: cholesterol granuloma and tympanosclerosis Source: Ear Research Institute; Year: 1978; Format: Videorecording; [Los Angeles]: The Institute, c1978

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Diagnosis and treatment of acute otitis media [videorecording] Source: an Autograph Communications production; Year: 1997; Format: Videorecording; [Canada?]: Autograph Communications; Boynton Beach, Fl: Distributed by UHC, c1996

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Evidence-based otitis media Source: Richard M. Rosenfeld, Charles D. Bluestone; Year: 1999; Format: Edited by; Hamilton, Ont.; Saint Louis: Decker, 1999

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Evidence-based otitis media Source: Richard M. Rosenfeld, Charles D. Bluestone; Year: 2003; Format: Edited by; Hamilton, Ont.: Lewiston, N.Y.: B.C. Decker, 2003

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Managing otitis media with effusion in young children [videorecording]: AHCPR clinical practice guideline Source: Sylvan E. Stool; Year: 1995; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1995

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Otitis media in children [videorecording] Source: presented by the Department of Pediatrics, Division of Infectious Diseases, Emory University, School of Medicine; Year: 1984; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1984

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Otitis media in children [videorecording]: when parents ask for antibiotics Source: Thomas G. Irons; Year: 1999; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1999

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Recent advances in otitis media with effusion [electronic resource]: proceedings of the seventh international symposium, June 1-5, 1999, Ft. Lauderdale, Florida Source: sponsored by Children's Hospital of Pittsburgh, Department of Pediatric Otolaryngology.; Year: 2002; Format: Electronic resource; Hamilton, Ont.; Lewiston, NY: B.C. Decker, c2002

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Recent advances in otitis media with effusion [videorecording] Source: ISDS; [produced by] Penn State Television; Year: 1980; Format: Videorecording; University Park, Pa.: WPSX-TV, 1980

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Serous otitis media & otitis media; Chronic otitis media [videorecording]: medical and surgical treatment Source: presented by the House Ear Institute; Year: 1985; Format: Videorecording; [Los Angeles, Calif.]: The Institute, c1985

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Serous otitis media [slide] Source: University of Michigan Medical Center; Year: 1974; Format: Slide; [Ann Arbor]: The University: [for sale by its Medical Center

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Serous otitis media [videorecording] Source: Brooke Army Medical Center; Year: 1972; Format: Videorecording; Fort Sam Houston, Tex.: Academy of Health Sciences, 1972

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Serous otitis media [videorecording] Source: sponsored by the House Ear Institute; Year: 1982; Format: Videorecording; [Los Angeles]: The Institute, c1982

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Serous otitis media [videorecording] Source: produced in the facilities of LSU Medical Television, in cooperation with LSU Family Medicine, and LSU Continuing Medical Education; Year: 1980; Format: Videorecording; [New Orleans, La.]: LSU Medical Center, c1980

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Serous otitis media [videorecording]: Gottschalk treatment Source: Ear Research Institute; Year: 1978; Format: Videorecording; [Los Angeles]: The Institute, c1978

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CHAPTER 9. PERIODICALS AND NEWS ON OTITIS MEDIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover otitis media.

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

Antihistamine therapy may prolong effusions with acute otitis media Source: Reuters Industry Breifing Date: October 01, 2003

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Adjuvant manipulative therapy may improve management of recurrent otitis media Source: Reuters Medical News Date: September 29, 2003

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Flu vaccine does not reduce acute otitis media in young children Source: Reuters Industry Breifing Date: September 24, 2003

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Otitis media sequelae decrease over time after tube placement Source: Reuters Medical News Date: May 26, 2003

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Otitis media-related hearing loss not linked with decrease in academic skills Source: Reuters Medical News Date: October 11, 2002

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Intranasal influenza vaccine prevents recurrent acute otitis media in children Source: Reuters Industry Breifing Date: August 08, 2002

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FDA okays Pfizer's Zithromax as one-dose treatment for pediatric otitis media Source: Reuters Industry Breifing Date: December 17, 2001

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S. pneumoniae and H. influenzae prevail after acute otitis media treatment Source: Reuters Industry Breifing Date: December 11, 2001

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Laser treatment can offer quick symptom relief of acute otitis media Source: Reuters Medical News Date: October 22, 2001

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High-dose amoxicillin/clavulanate highly efficacious for acute otitis media Source: Reuters Industry Breifing Date: October 08, 2001

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Behaviour and cognitive problems can persist for children with otitis media Source: Reuters Medical News Date: September 03, 2001

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Antibiotics offer limited benefit for children with acute otitis media Source: Reuters Medical News Date: August 06, 2001

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Naturopathic ear drops relieve pain associated with acute otitis media Source: Reuters Medical News Date: July 26, 2001

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Steroid use not recommended for otitis media with effusion Source: Reuters Industry Breifing Date: June 19, 2001

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Pediatrician management of otitis media often falls short of guidelines Source: Reuters Industry Breifing Date: June 18, 2001

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Low cord blood antibody levels predict otitis media in infants Source: Reuters Medical News Date: May 29, 2001

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Topical otic anesthetic might reduce need for antibiotics in acute otitis media Source: Reuters Industry Breifing Date: May 01, 2001

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Tympanostomy tube insertion for otitis media clarified Source: Reuters Medical News Date: April 18, 2001

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Ventilation tubes do not improve QOL in children with persistent otitis media Source: Reuters Medical News Date: February 19, 2001

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Antibiotic therapy for acute otitis media can be delayed until needed Source: Reuters Industry Breifing Date: February 08, 2001

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New vaccine against acute otitis media safe and effective Source: Reuters Medical News Date: February 07, 2001

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Bacterial spray reduces infection rate in children at high risk of acute otitis media Source: Reuters Medical News Date: January 25, 2001

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Multiple-dose ceftriaxone effective in nonresponsive otitis media Source: Reuters Industry Breifing Date: December 28, 2000

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Amoxicillin/clavulanate reduces nasopharyngeal carriage in acute otitis media Source: Reuters Industry Breifing Date: November 10, 2000

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Otitis media guidelines may not be affecting US physician practice patterns Source: Reuters Industry Breifing Date: September 26, 2000

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Pacifier use a preventable risk factor for acute otitis media in infants Source: Reuters Medical News Date: September 06, 2000

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Early episode of acute otitis media predicts persistent otitis media with effusion Source: Reuters Medical News Date: August 18, 2000

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Antibiotics of limited benefit in pediatric acute otitis media Source: Reuters Industry Breifing Date: August 10, 2000

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Low transplacental type 14 pneumococcal IgG1 linked to early otitis media Source: Reuters Medical News Date: July 12, 2000

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Repeated air inflation prevents otitis media with effusion in monkeys Source: Reuters Medical News Date: May 26, 2000

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Protein fragment prevents mucosal damage in rat model of otitis media with effusion Source: Reuters Medical News Date: May 08, 2000

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Routine use of steroids for treatment of otitis media called into question Source: Reuters Medical News Date: March 03, 2000

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Initial antibiotics not warranted in young children with acute otitis media Source: Reuters Medical News Date: February 11, 2000

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Genetics involved in otitis media and middle ear effusion Source: Reuters Medical News Date: December 08, 1999

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Laser-assisted myringotomy effective treatment for otitis media Source: Reuters Medical News Date: October 11, 1999

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Adenoidectomy, adenotonsillectomy: limited efficacy against recurrent acute otitis media Source: Reuters Medical News Date: September 08, 1999

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Amoxicillin/clavulanate superior to azithromycin in treatment of acute otitis media Source: Reuters Medical News Date: May 06, 1999

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Timing of surgery for otitis media with effusion does not affect speech Source: Reuters Medical News Date: March 22, 1999

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First-line, second-line antibiotics equally effective in recurrent otitis media Source: Reuters Medical News Date: February 08, 1999

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RSV is the "principal virus" in otitis media Source: Reuters Medical News Date: January 28, 1999

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Amoxicillin remains the drug of choice for acute otitis media Source: Reuters Medical News Date: January 20, 1999

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FDA approves 5-day treatment for acute otitis media Source: Reuters Medical News Date: November 25, 1998

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Longer antibiotic treatment benefits children younger than 2 with acute otitis media Source: Reuters Medical News Date: November 24, 1998

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Environmental factors related to number of clinic visits for otitis media Source: Reuters Medical News Date: October 19, 1998

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Sweetener reduces incidence of acute otitis media in children by more than one third Source: Reuters Medical News Date: October 06, 1998

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Incidence of acute otitis media increasing Source: Reuters Medical News Date: October 01, 1998

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Amoxicillin/clavulanate more effective than azithromycin in treatment of acute otitis media Source: Reuters Medical News Date: September 30, 1998

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Otitis media treatable with office-based laser-assisted myringotomy Source: Reuters Medical News Date: September 18, 1998

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Link between otitis media, home environment and learning problems reported Source: Reuters Medical News Date: August 04, 1998

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Resistance to oral cephalosporins high in otitis media cases after failed antibiotic therapy Source: Reuters Medical News Date: June 23, 1998 The NIH

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

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

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

Earache and Ear Tubes: Acute Otitis Media Manifests Itself in a Feeling of Pressure in the Ear Source: From Your Shoulders Up. 4(1): 1. Winter 1994-95. Contact: Available from American Academy of Otolaryngology-Head and Neck Surgery, Inc. (AAOHNS). One Prince Street, Alexandria, VA 22314. (703) 836-4444. Fax (703) 683-5100. Website: www.ent.org. Summary: This brief article, from a patient education newsletter, discusses acute otitis media. Topics covered include the causes of otitis media; symptoms, especially in children; otitis media-related hearing loss and the problems it can cause in language development and learning capacity; the use of tubes to drain a child's ears; complications associated with ear tubes; the role of antibiotics; the benefits of ventilation ear tubes; and the problem of antibiotic-resistant bacteria.

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

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periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to otitis media: Antihistamines •

Systemic - U.S. Brands: Aller-Chlor; AllerMax Caplets; Aller-med; Atarax; Banophen; Banophen Caplets; Benadryl; Benadryl Allergy; Bromphen; Calm X; Chlo-Amine; Chlorate; Chlor-Trimeton; Chlor-Trimeton Allergy; Chlor-Trimeton Repetabs; Claritin; Claritin Reditabs; Compoz; Conta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202060.html

Antihistamines and Decongestants •

Systemic - U.S. Brands: A.R.M. Maximum Strength Caplets; Actagen; Actifed; Actifed Allergy Nighttime Caplets 20; Alcomed; Alcomed 2-60; Allent; Allercon; Allerest Maximum Strength; Allerfrim; Allerphed; Amilon; Anamine; Anamine T.D.; Andec; Andec-TR; Aprodrine; Atrofed; Atrohi http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202061.html

Azithromycin •

Systemic - U.S. Brands: Zithromax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202642.html

Cephalosporins •

Systemic - U.S. Brands: Ancef; Ceclor; Ceclor CD; Cedax; Cefadyl; Cefizox; Cefobid; Cefotan; Ceftin; Cefzil; Ceptaz; Claforan; Duricef; Fortaz; Keflex 20; Keftab 20; Kefurox; Kefzol; Mandol; Maxipime; Mefoxin; Monocid; Omnicef; Rocephin; Suprax; Tazicef; Tazidime; Vantin; Velo http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202119.html

Clarithromycin •

Systemic - U.S. Brands: Biaxin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202667.html

Erythromycin •

Ophthalmic - U.S. Brands: Ilotycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202220.html

Loracarbef •

Systemic - U.S. Brands: Lorabid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202680.html

Penicillins •

Systemic - U.S. Brands: Amoxil; Bactocill; Beepen-VK; Betapen-VK; Bicillin L-A; Cloxapen; Crysticillin 300 A.S.; Dycill; Dynapen; Geocillin; Geopen; Ledercillin VK; Mezlin; Nafcil; Nallpen; Omnipen; Omnipen-N; Pathocil; Pen Vee K; Pentids; Permapen; Pfizerpen; Pfizerpen-AS; Pi http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202446.html

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Sulfonamides •

Ophthalmic - U.S. Brands: Ak-Sulf; Bleph-10; Cetamide; Gantrisin; IsoptoCetamide; I-Sulfacet; Ocu-Sul-10; Ocu-Sul-15; Ocu-Sul-30; Ocusulf-10; Ophthacet; Sodium Sulamyd; Spectro-Sulf; Steri-Units Sulfacetamide; Sulf-10; Sulfair; Sulfair 10; Sulfair 15; Sulfair Forte; Sulfamide; http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202539.html

•

Systemic - U.S. Brands: Gantanol; Gantrisin; Thiosulfil Forte; Urobak http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202540.html

•

Vaginal - U.S. Brands: AVC; Sultrin; Trysul http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202541.html

Trimethoprim •

Systemic - U.S. Brands: Proloprim; Trimpex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202579.html

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

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

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

224 Otitis Media

through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

225

APPENDICES

227

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 Institute12: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

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.13 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:14 •

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

13

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). 14 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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “otitis media” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “otitis media” (or synonyms) into the “For these words:” box. The following is a sample result: •

Otitis media in children and later language and learning Source: Arlington, VA: National Center for Education in Maternal and Child Health. 1997. 9 pp. Contact: Available from Librarian, National Center for Education in Maternal and Child Health, 2000 15th Street, North, Suite 701, Arlington, VA 22201-2617. Telephone: (703) 524-7802 / fax: (703) 524-9335 / e-mail: [email protected] / Web site: http://www.ncemch.org. Photocopy available at no charge; also available from the Web site at no charge. Summary: This report summarizes a Maternal and Child Health Bureau funded project presented at a seminar February 26, 1997. The project examines the relationship between otitis media with effusion in children and its associated hearing loss during early childhood with the development of language and learning during the preschool years. The report ends with reaction to the project and a list of publications. [Funded by the Maternal and Child Health Bureau].

The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “otitis media” (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.

15 16

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

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 17813 293 872 133 11 19122

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “otitis media” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 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.21 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.22 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/.

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

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

19

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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

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

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

•

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

The Genome Project and Otitis Media In the following section, we will discuss databases and references which relate to the Genome Project and otitis media. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “otitis media” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for otitis media: •

Otitis Media, Susceptibility to Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?166760 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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•

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

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

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

•

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

•

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

•

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

•

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

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

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

234 Otitis Media

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “otitis media” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.

24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

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The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “otitis media” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

237

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 otitis media 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 otitis media. 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 otitis media. 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 “otitis media”:

238 Otitis Media

•

Other guides Children's Health http://www.nlm.nih.gov/medlineplus/childrenshealth.html Ear Disorders http://www.nlm.nih.gov/medlineplus/eardisorders.html Ear Infections http://www.nlm.nih.gov/medlineplus/earinfections.html Hearing Disorders & Deafness http://www.nlm.nih.gov/medlineplus/hearingdisordersdeafness.html Infant and Toddler Health http://www.nlm.nih.gov/medlineplus/infantandtoddlerhealth.html

Within the health topic page dedicated to otitis media, the following was listed: •

General/Overviews Acute Otitis Media (Ear Infection) Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/otitis_media.html JAMA Patient Page: Acute Otitis Media Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZIDXIZZKD& sub_cat=554 Otitis Media http://www.nlm.nih.gov/medlineplus/tutorials/otitismedialoader.html

•

Diagnosis/Symptoms Ear Problems Source: American Academy of Family Physicians http://familydoctor.org/507.xml

•

Treatment Ear Infections and Ear Tube Surgery Source: Nemours Foundation http://kidshealth.org/parent/medical/ears/ear_infections.html

•

Alternative Therapy Chiropractic Approach to the Ear Source: American Chiropractic Association http://www.amerchiro.org/media/tips/ear_chiropractic.shtml

Patient Resources

•

239

Specific Conditions/Aspects “Swimmer's Ear” (Otitis Externa) Source: National Center for Infectious Diseases, Division of Parasitic Diseases http://www.cdc.gov/healthyswimming/swimmers_ear.htm Cholesteatoma Source: American Academy of Otolaryngology--Head and Neck Surgery http://www.entnet.org/healthinfo/ears/cholesteatoma.cfm Fluid in the Middle Ear (Otitis Media with Effusion) http://www.cdc.gov/antibioticresistance/files/ome.pdf Perforated Eardrum Source: American Academy of Otolaryngology--Head and Neck Surgery http://www.entnet.org/healthinfo/ears/perforation.cfm

•

Children Causes of Hearing Loss in Children Source: American Speech-Language-Hearing Association http://www.asha.org/public/hearing/disorders/causes.htm Children's Middle Ear Infections Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/takecharge/healthdecisionguides/childrensmiddleea rinjury/index.cfm Ear Infection Quiz Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=QZ00026 Swimmer's Ear Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/aches/swimmers_ear.html Taking Care of Your Ears Source: Nemours Foundation http://kidshealth.org/kid/stay_healthy/body/ear_care.html What Is an Ear Infection? Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/sick/ear_infection.html

•

Organizations American Academy of Otolaryngology--Head and Neck Surgery http://www.entnet.org/ National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/

•

Pictures/Diagrams Atlas of the Body: The Ear Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZYXNW46JC

240 Otitis Media

&sub_cat=198 •

Research Bacteria-Rich 'Biofilm' May Give Rise to Chronic Otitis Media Source: National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/news/releases/02/4_03_02.asp Many Parents Willing to Wait on Antibiotic Prescriptions for Ear Infections Source: Nemours Foundation http://kidshealth.org/research/antibiotic_rx.html Reduced: Unnecessary Antibiotics for Children Source: National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/news/releases/02/6_25_02.asp Study Confirms Safety of Placing Infants to Sleep on Their Backs Source: National Institute of Child Health and Human Development, National Institute on Deafness and Other Communication Disorders http://www.nih.gov/news/pr/may2003/nichd-12.htm

•

Teenagers External Otitis (Swimmer's Ear) Source: Nemours Foundation http://kidshealth.org/teen/infections/bacterial_viral/swimmers_ear.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on otitis media. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Chronic Otitis Media (Middle Ear Infection) and Hearing Loss Source: Alexandria, VA: American Academy of Otolaryngology-Head and Neck Surgery. 2003. Contact: Available from American Academy of Otolaryngology-Head and Neck Surgery. One Prince St., Alexandria, VA 22314-3357. (703) 836-4444. TTY: (703) 519-1585. Web site: www.entnet.org/kidsent. PRICE: Available free online.

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Summary: Chronic ear infections, if left untreated, can cause temporary or permanent hearing loss in a child. This fact sheet describes what otitis media is as well as how otitis media affects a child's hearing. The two types of hearing loss, the appropriate time for having a child's hearing tested, and other possible causes of temporary hearing loss are also described. •

Otitis Media: Facts for Parents Source: Bethesda, MD: National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH). September 2000. 12 p. Contact: Available from NIDCD Information Clearinghouse. 1 Communication Avenue, Bethesda, MD 20892-3456. Voice (800) 241-1044. TTY (800) 241-1055. Fax (301) 907-8830. E-mail: [email protected]. Website: www.nidcd.nih.gov. PRICE: Single copy free. NIH Publication Number 00-4216. Summary: Otitis media is an infection of the middle ear, a common occurrence in babies and young children. This brochure reviews the different types of otitis media (acute otitis media, or AOM, and otitis media with effusion, also called OME), how otitis media occurs, what is happening inside the ear of a child with otitis media, how otitis media can affect the child's hearing, the symptoms of otitis media, determining if the child needs to be seen by a health care provider, the types of medications used to treat otitis media and how they are used, recordkeeping to keep track of a child's medications, the use of surgical techniques to treat chronic problems with otitis media (with a myringotomy, or ventilation tubes), concerns about daycare or school settings, and preventive steps that parents can take (notably, not smoking around the child). The booklet concludes with a listing of resource organizations through which parents can get more information. The brochure is illustrated with simple line drawings. 7 figures.

•

Middle Ear Fluid in Young Children: Otitis Media with Effusion-Parent Guide Source: Rockville, MD: Agency for Health Care Policy and Research (AHCPR), Public Health Service, U.S. Department of Health and Human Services. July 1994. 16 p. Contact: Available Agency for Health Care Policy and Research (AHCPR) Publications Clearinghouse. P.O. Box 8547, Silver Spring, MD 20907-8547. (800) 358-9295. PRICE: Single copy free. Also available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. PRICE: Single copy free; bulk rates available. Summary: This booklet discusses middle ear fluid in children ages 1 through 3 who have no other health problems. Middle ear fluid, sometimes known as 'glue ear', is otitis media with effusion. In other words, it is a middle ear inflammation with fluid. Topics covered include the causes of middle ear fluid, tests for middle ear fluid and hearing, treatments for middle ear fluid and hearing loss caused by middle ear fluid, and how to work with the child's health care provider to find the best treatment for each individual child. The brochure also includes a description of the anatomy and function of the ear and hearing. The inside back cover of the brochure provides a blank chart for parents to track the child's ear problems and how they were treated.

•

Doctor, Why Does My Child's Ear Ache?. Insights Into Otitis Media and Treatments Source: Alexandria, VA: American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. (AAO-HNS). 2001. 4 p.

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Contact: Available from American Academy of Otolaryngology-Head and Neck Surgery, Inc. One Prince Street, Alexandria, VA 22314. (703) 836-4444. Fax ( Website: www.entnet.org. PRICE: $20.00 for 100 (members); $25.00 for 100 (non-members). Summary: This brochure helps parents understand otitis media (middle ear infection, a common cause of earache) and its treatments. Written in a question and answer format, the brochure defines otitis media, discusses its severity and why it should be treated, describes how the ear works to maintain hearing and balance, notes the symptoms of otitis media, reviews the causes of the condition, and explains what will happen at the doctor's office. The brochure concludes with a discussion of the use of medications to treat otitis media, and reviews the indications for ventilation tubes (myringostomy) in children. The brochure emphasizes the negative impact that ear infections can have on the child's hearing. Even a temporary or mild hearing loss may impair learning capacity and can delay speech development. The back page of the brochure offers a brief description of the medical specialty of otolaryngology-head and neck surgery. 3 figures. •

Earache and Otitis Media Source: Alexandria, VA: American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. (AAO-HNS). 1993. [4 p.]. Contact: American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. (AAO-HNS). One Prince Street, Alexandria, VA 22314-3357. (703) 836-4444. Fax (703) 683-5100. Website: www.entnet.org. PRICE: Single copy free (send self-addressed, stamped envelope); $20.00 per 100 for members; $25.00 per 100 for non-members. Item Number 4763180. Summary: This brochure provides basic information about earaches and otitis media (middle ear infection). The brochure notes that otitis media can be serious because of accompanying hearing loss which can impact on a child's language development. In order to avoid these complications, the brochure encourages parents to get any ear problems treatment as soon as possible. Other topics include the middle ear and how it functions, the causes of otitis media, the symptoms of otitis media, the doctor's examination for an ear infection, the use and importance of medication to treat ear infections, and the additional treatments that may be necessary, including the use of ventilation tubes (myringostomy). The brochure concludes with a brief description of the specialty of otolaryngology-head and neck surgery. 1 figure.

•

Ear Infection, Middle (Otitis Media) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Orlando, FL: W.B. Saunders Company. 1994. p. 141. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522; Fax (800) 874-6418. PRICE: $47.50 plus shipping and handling. ISBN: 0721649300. Summary: This fact sheet on otitis media (middle ear infection) is from a compilation of instructions for patients, published in book format. The fact sheet provides information in three sections: basic information, including a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. The fact sheet is designed to be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool.

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Otitis Media Source: Bethesda, MD: National Institute on Deafness and Other Communication Disorders (NIDCD). March 1997. [5 p.]. Contact: Available from National Institute on Deafness and Other Communication Disorders (NIDCD) Information Clearinghouse. 1 Communication Avenue, Bethesda, MD 20892-3456. Voice (800) 241-1044. TTY (800) 241-1055. Fax (301) 907-8830. E-mail: [email protected]. Website: www.nidcd.nih.gov. PRICE: Single copy free. NIH Publication Number 97-4216. Summary: This fact sheet presents information about otitis media, an infection or inflammation of the middle ear. This inflammation often begins when infections that cause sore throats, colds, or other respiratory or breathing problems spread to the middle ear. The fact sheet, written in question and answer format, first describes the basic anatomy of the ear and the physiology of hearing. Other topics covered include the causes of otitis media, why children are more affected by this problem than are adults, the symptoms of otitis media, the complications that can be caused by the condition, prevention strategies, how otitis media is diagnosed, treatment options, and current research activities in this area. Although the hearing loss caused by otitis media is usually temporary, untreated otitis media may lead to permanent hearing impairment. In addition, persistent fluids in the middle ear and chronic otitis media can reduce a child's hearing at a time that is critical for speech and language development. The fact sheet concludes with the contact information for four related resource organizations.

•

Otitis Media and Speech and Language Development Source: in Schrader, M., ed. Parent Articles 1: Enhance Parent Involvement in Language Learning. San Antonio, TX: Communication Skill Builders. 1988. p. 173-175. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; TTY (800) 723-1318; Fax (800) 2321223. PRICE: $52.00 plus shipping and handling. Order Number 076-1674-39X-MS799. Summary: This fact sheet provides parents with information on otitis media and its impact on speech and language development. Topics covered include a definition of otitis media, its symptoms, recurrent otitis media, problems that can be caused by recurrent otitis media, what parents can do to help, and suggestions for activities parents can do to improve their child's communication skills during everyday activities. The author also provides a list of related vocabulary terms. The fact sheet is one of a series of instructional materials designed to enhance parent involvement in language learning. The fact sheets share information on speech therapy and speech/language disorders targeted to parents of children 1 to 7 years old. The fact sheets also answer frequently-asked questions and suggest related activities to enhance children's speech and language skills.

•

Middle Ear Fluid: Serous Otitis Media Source: San Bruno, CA: Staywell Company. 2000. 2 p. Contact: Available from Staywell Company. Order Department, 100 Grundy Lane, San Bruno, CA 94066-3030. (800) 333-3032. PRICE: Single copy free; $0.40 each for multiple copies; bulk discounts available. Order Number 1101. Summary: This patient education brochure describes the problem of serous otitis media (middle ear fluid) in both children and adults. After a description of the problem, the

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brochure covers Eustachian tube function; Eustachian tube anatomy in children and in adults; treatment options, including the surgical technique of tympanotomy; and postoperative care. The brochure stresses that treatment of serous otitis media is designed to restore ventilation to the middle ear. Medications and allergy management may open the Eustachian tube and reduce fluid secretion; when needed, a tympanotomy, with or without tube insertion, can be used to allow air to flow into the middle ear cavity. 2 figures. (AA-M). •

Clinical Practice Guideline: Managing Otitis Media with Effusion in Young Children Source: Rockville, MD: Agency for Health Care Policy and Research (AHCPR). 1994. 16 p. Contact: Available from AHCPR Publications Clearinghouse. P.O. Box 8547, Silver Spring, MD 20907. (800) 358-9295. PRICE: Single copy free. AHCPR Publication Number 94-0623. Summary: This Quick Reference Guideline for Clinicians contains highlights from the Clinical Practice Guideline discussing otitis media with effusion in young children. Specific recommendations are given for the management of otitis media with effusion in young children age 1 through 3 years with no craniofacial or neurologic abnormalities or sensory deficits. The natural history of otitis media with effusion, the functional impairments that may result from otitis media with effusion, and the difficulty of measuring the effects of medical and surgical interventions on long-term outcomes are included. The medical interventions covered include antibiotic therapy, steroid therapy, and antihistamine/decongestant therapy. The surgical interventions studied include myringotomy with insertion of tympanostomy tubes, adenoidectomy, and tonsillectomy. Short-term outcomes addressed are resolution of effusion and restoration of hearing. 1 treatment algorithm is also included. 1 table. 13 references. (AA-M). The National Guideline Clearinghouse™

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

Acute otitis media: management and surveillance in an era of pneumococcal resistance Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1705&nbr=931&am p;string=otitis+AND+media

•

Diagnosis and treatment of otitis media in children Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 May (revised 2002 Dec); 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3667&nbr=2893&a mp;string=otitis+AND+media

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Evidence based clinical practice guideline for medical management of otitis media in children 2 months to 6 years of age Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1999 http://www.guideline.gov/summary/summary.aspx?doc_id=1972&nbr=1198&a mp;string=otitis+AND+media

•

Otitis media Source: University of Michigan Health System - Academic Institution; 1997 November (revised 2002 May); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3371&nbr=2597&a mp;string=otitis+AND+media

•

Screening for otitis media with effusion. Recommendation statement from the Canadian Task Force on Preventive Health Care Source: Canadian Task Force on Preventive Health Care - National Government Agency [Non-U.S.]; 2001 October; 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3071&nbr=2297&a mp;string=otitis+AND+media Healthfinder™

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

Ear Infections: Facts for Parents About Otitis Media Summary: Written especially for parents, this fact sheet describes the different types of otitis media and its causes, symptoms, and treatment. Source: National Institute on Deafness and Other Communication Disorders Information Clearinghouse http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6666

•

Otitis Media (Ear Infection) Summary: Basic consumer health information about otitis media including a description, symptoms, diagnosis, prevention and treatment. Source: National Institute on Deafness and Other Communication Disorders Information Clearinghouse http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4502

246 Otitis Media

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 otitis media. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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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 “otitis media” (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 “otitis media”. 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 “otitis media” (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 “otitis media” (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.26

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

26

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)27: •

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

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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/

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

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

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

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

•

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/

27

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

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•

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

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

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

•

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

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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

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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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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/

•

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

•

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

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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 otitis media: •

Basic Guidelines for Otitis Media Chlamydia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001345.htm Influenza Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000080.htm Otitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001336.htm Otitis media - acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000638.htm Otitis media - chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000619.htm Otitis media with effusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/007010.htm

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Signs & Symptoms for Otitis Media Deafness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Decreased hearing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Drainage from the ear Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003042.htm Ear discomfort Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003046.htm Ear pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003046.htm Ear pain or discomfort Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003046.htm Earache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003046.htm Erythema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Hearing loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Irritability Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003214.htm Joint pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Loss of hearing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm

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Nasal congestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003049.htm Nasal discharge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003051.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Neck pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003025.htm Nystagmus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003037.htm Otalgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003046.htm Otorrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003042.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Throat, sore Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003053.htm Tinnitus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003043.htm Vertigo Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Otitis Media CT scan of the head Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm Mastoid X-rays Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003802.htm Tympanometry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003390.htm

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Surgery and Procedures for Otitis Media Adenoidectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003011.htm Myringotomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003015.htm Tonsillectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003013.htm Tympanostomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003015.htm

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Background Topics for Otitis Media Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Analgesic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Inspection Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002388.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm

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

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

•

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

•

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

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•

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

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OTITIS MEDIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections.

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Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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]

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

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in

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birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alpha-helix: One of the secondary element of protein. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH]

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Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

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Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH]

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Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] 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] Aseptic: Free from infection or septic material; sterile. [EU] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH]

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Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atelectasis: Incomplete expansion of the lung. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiologist: Study of hearing including treatment of persons with hearing defects. [NIH] Audiometry: The testing of the acuity of the sense of hearing to determine the thresholds of the lowest intensity levels at which an individual can hear a set of tones. The frequencies between 125 and 8000 Hz are used to test air conduction thresholds, and the frequencies between 250 and 4000 Hz are used to test bone conduction thresholds. [NIH] Audition: The sense of hearing. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Auditory Perception: The process whereby auditory stimuli are selected, organized and interpreted by the organism; includes speech discrimination. [NIH] Augmentin: An antibiotic. [NIH] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills,

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tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Adhesion: Physicochemical property of fimbriated and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Vaccines: Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease. [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] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barotrauma: Injury following pressure changes; includes injury to the eustachian tube, ear drum, lung and stomach. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders.

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Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Binaural: Used of the two ears functioning together. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotype: A group of individuals having the same genotype. [NIH] Bladder: The organ that stores urine. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]

Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]

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Blood Glucose: Glucose in blood. [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] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Conduction: Sound transmission through the bones of the skull to the inner ear. [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 Resorption: Bone loss due to osteoclastic activity. [NIH] Bottle Feeding: Use of nursing bottles for feeding. Applies to humans and animals. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Broadband: A wide frequency range. Sound whose energy is distributed over a broad range of frequency (generally, more than one octave). [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH]

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Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of

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occurrence). [EU] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefaclor: Semisynthetic, broad-spectrum antibiotic derivative of cephalexin. [NIH] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Cefuroxime: Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, gonorrhea, and haemophilus. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH]

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Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] 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] Cerumen: The yellow or brown waxy secretions produced by vestigial apocrine sweat glands in the external ear canal. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Child Care: Care of children in the home or institution. [NIH] Child Development: The continuous sequential physiological and psychological maturing of the child from birth up to but not including adolescence. It includes healthy responses to situations, but does not include growth in stature or size (= growth). [NIH] Child Language: The language and sounds expressed by a child at a particular maturational stage in development. [NIH] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours

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unless quickly treated. [NIH] Cholesteatoma: A non-neoplastic keratinizing mass with stratified squamous epithelium, frequently occurring in the meninges, central nervous system, bones of the skull, and most commonly in the middle ear and mastoid region. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Circumcision: Excision of the prepuce or part of it. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH]

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Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Implantation: Surgical insertion of an electronic device implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [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] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [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] Colloidal: Of the nature of a colloid. [EU] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian

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plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [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] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH]

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Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Conjunctivitis, Allergic: Conjunctivitis due to hypersensitivity to various allergens. [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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]

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Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronavirus: A genus of the family Coronaviridae which causes respiratory or gastrointestinal disease in a variety of vertebrates. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into

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three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Custom-made: Any active implantable medical device specifically made in accordance with a medical specialist's written prescription which gives, under his responsibility, specific design characteristics and is intended to be used only for an individually named patient. [NIH]

Cutaneous: Having to do with the skin. [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] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [NIH] Cytidine Triphosphate: Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU]

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Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decongestant: An agent that reduces congestion or swelling. [EU] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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]

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Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextrorotatory: Turning towards the right hand. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal

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consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysostosis: Defective bone formation. [NIH] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ear Diseases: Diseases of the ear, general or unspecified. [NIH] Earache: Pain in the ear. [NIH] Eardrum: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Echinacea: A genus of perennial herbs used topically and internally. It contains echinacoside, glycosides, inulin, isobutyl amides, resin, and sesquiterpenes. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH]

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Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune

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and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [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] Enhancer: Transcriptional element in the virus genome. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental tobacco smoke: ETS. Smoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers (second-hand smoke). Inhaling ETS is called involuntary or passive smoking. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other health-

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related event occurring in such outbreaks. [EU] Epidemiologic Factors: Events, characteristics, or other definable entities that have the potential to bring about a change in a health condition or other defined outcome. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [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] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] 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]

Equalization: The reduction of frequency and/or phase distortion, or modification of gain and or phase versus frequency characteristics of a transducer, by the use of attenuation circuits whose loss or delay is a function of frequency. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH]

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Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] 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] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU]

Dictionary 287

Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in

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carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [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] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous

Dictionary 289

tissue of the eyelid discharging pus from several points. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Gland: An organ that produces and releases one or more substances for use in the body.

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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. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glossopalatine: A root of the facial nerve arising from the sensory nucleus, lateral and posterior to the motor root, containing parasympathetic fibers coursing to the lacrimal gland via the great superficial petrosal nerve which synapses in the sphenopalatine ganglion. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH]

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Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [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] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH]

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Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hammer: The largest of the three ossicles of the ear. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemin:

Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-

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dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. [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 A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatomegaly: Enlargement of 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] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird

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and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires

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and strivings of the individual. [NIH] Immaturity: The state or quality of being unripe or not fully developed. [EU] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU]

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In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Incus: One of three ossicles of the middle ear. It conducts sound vibrations from the malleus to the stapes. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease.

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[NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is

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also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [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] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] 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] Ipsilateral: Having to do with the same side of the body. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body.

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Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Labyrinthitis: Inflammation of the inner ear. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal Apparatus: The tear-forming and tear-conducting system which includes the lacrimal glands, eyelid margins, conjunctival sac, and the tear drainage system. [NIH] Lactoperoxidase: An enzyme derived from cow's milk. It catalyzes the radioiodination of tyrosine and its derivatives and of peptides containing tyrosine. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH]

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Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Language Development Disorders: Conditions characterized by language abilities (comprehension and expression of speech and writing) that are below the expected level for a given age, generally in the absence of an intellectual impairment. These conditions may be associated with deafness; brain diseases; mental disorders; or environmental factors. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Language Therapy: Rehabilitation of persons with language disorders or training of children with language development disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by

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oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkages: 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] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to

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humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH]

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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] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

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

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mannosidosis: Inborn error of metabolism marked by a defect in alpha-mannosidase

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activity that results in lysosomal accumulation of mannose-rich substrates. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder. [NIH] Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastoiditis: Inflammation of the cavity and air cells in the mastoid part of the temporal bone. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [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]

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Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Meningococcal Infections: Infections with bacteria of the species neisseria meningitidis. [NIH]

Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] 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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]

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Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Middle Ear Ventilation: Ventilation of the middle ear in the treatment of secretory (serous) otitis media, usually by placement of tubes or grommets which pierce the tympanic membrane. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular 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] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes

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(monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]

Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mouth Breathing: Abnormal breathing through the mouth, usually associated with obstructive disorders of the nasal passages. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucociliary Clearance: Rate of ciliary and secretory activity of the respiratory submucosal glands. It is a non-specific host defense mechanism, measurable in vivo by mucus transfer, ciliary beat frequency, and clearance of radioactive tracers. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Mupirocin: A topically used antibiotic from a strain of Pseudomonas fluorescens. It has shown excellent activity against gram-positive staphylococci and streptococci. The antibiotic is used primarily for the treatment of primary and secondary skin disorders, nasal infections, and wound healing. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and

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smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [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] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Nasolacrimal: Pertaining to the nose and lacrimal apparatus. [EU] Nasopharyngitis: Inflammation of the nasopharynx. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH]

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NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neisseria: A genus of gram-negative, aerobic, coccoid bacteria whose organisms are part of the normal flora of the oropharynx, nasopharynx, and genitourinary tract. Some species are primary pathogens for humans. [NIH] Neisseria meningitidis: A species of gram-negative, aerobic bacteria found in cerebrospinal fluid as the causative agent of cerebrospinal meningitis (meningitis, meningococcal) as well as in venereal discharges and blood. [NIH] Neodymium: Neodymium. An element of the rare earth family of metals. It has the atomic symbol Nd, atomic number 60, and atomic weight 144.24, and is used in industrial applications. [NIH] Neon: Neon. A noble gas with the atomic symbol Ne, atomic number 10, and atomic weight 20.18. It is found in the earth's crust and atmosphere as an inert, odorless gas and is used in vacuum tubes and incandescent lamps. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] 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] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From

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Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrite Reductases: A group of enzymes that oxidize diverse nitrogenous substances to yield nitrite. (Enzyme Nomenclature, 1992) EC 1. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Noel: The highest dose level of a chemical that, in a given toxicity test, causes no observable adverse effect in the test animals. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] 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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH]

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Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Oculi: Globe or ball of the eye. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH]

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Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Orderly: A male hospital attendant. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossicle: A small bone. [EU] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otitis Media with Effusion: Inflammation of the middle ear with a clear pale yellowcolored transudate. [NIH] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [NIH] Otorhinolaryngology: That branch of medicine concerned with medical and surgical treatment of the head and neck, including the ears, nose and throat. [EU] Otorrhea: A discharge from the ear, especially a purulent one. [EU] Otosclerosis: The formation of spongy bone in the labyrinth capsule. The ossicles can become fixed and unable to transmit sound vibrations, thereby causing deafness. [NIH] Outer ear: The pinna and external meatus of the ear. [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] Oval Window: Fenestra of the vestibule; an oval opening in the medial wall of the middle ear leading into the vestibule. Normally it is covered by the base of the stapes. [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)

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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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palatal Muscles: The muscles of the palate are the glossopalatine, palatoglossus, levator palati(ni), musculus uvulae, palatopharyngeus, and tensor palati(ni). [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness,

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occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perceptual Masking: The interference of one perceptual stimulus with another causing a decrease or lessening in perceptual effectiveness. [NIH] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] 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]

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Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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]

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Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH]

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Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pneumococcal Infections: Infections with bacteria of the species Streptococcus pneumoniae. [NIH]

Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] 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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful

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substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Povidone: A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander. [NIH] Povidone-Iodine: An iodinated polyvinyl polymer used as topical antiseptic in surgery and for skin and mucous membrane infections, also as aerosol. The iodine may be radiolabeled for research purposes. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body,

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secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15-

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hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostatitis: Inflammation of the prostate. [EU] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease

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characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychoacoustic: That branch of psychophysics dealing with acoustic stimuli. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychophysics: The science dealing with the correlation of the physical characteristics of a stimulus, e.g., frequency or intensity, with the response to the stimulus, in order to assess the psychologic factors involved in the relationship. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring systems. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not

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sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in

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crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH]

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Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] 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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Respiratory Syncytial Virus Infections: Pneumovirus infections caused by the respiratory syncytial viruses. Humans and cattle are most affected but infections in goats and sheep have been reported. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH]

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Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Round Window: Fenestra of the cochlea; an opening in the medial wall of the middle ear leading into the cochlea. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Saccule: The smaller of the 2 sacs within the vestibule of the ear. [NIH] Saline: A solution of salt and water. [NIH]

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Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU]

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Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [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]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH]

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Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH]

Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or

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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] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Speech Perception: The process whereby an utterance is decoded into a representation in terms of linguistic units (sequences of phonetic segments which combine to form lexical and grammatical morphemes). [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] 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] Spiral Lamina: The bony plate which extends outwards from the modiolus. It is part of the structure which divides trhe cochlea into sections. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stapedius: The stapedius muscle arises from the wall of the middle ear and is inserted into the neck of the stapes. Its action is to pull the head of the stapes backward. [NIH] Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Sterile: Unable to produce children. [NIH] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU]

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Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [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] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submucous: Occurring beneath the mucosa or a mucous membrane. [NIH] 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.

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[NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sulfisoxazole: One of the antibacterial sulfonamides generally used for treatment of infections. It is bacteriostatic against a wide range of gram- negative and gram-positive organisms, but acquired resistance is common. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Surdity: Deafness. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] T cell: One type of white blood cell that attacks virus-infected cells, foreign cells, and cancer cells. T cells also produce a number of substances that regulate the immune response. [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]

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Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]

Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators

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of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonal: Based on special tests used for a topographic diagnosis of perceptive deafness (damage of the Corti organ, peripheral or central damage, i. e. the auditive cortex). [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonsil: A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the pharynx situated on each side of the fauces, between the anterior and posterior pillars of the soft palate. [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] 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

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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] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [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] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH]

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Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tympani: The part of the cochlea below the spiral lamina. [NIH] Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Tympanum: 1. Loosely, the tympanic membrane (membrana tympani). 2. The tympanic cavity (cavitas tympanica). [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

336 Otitis Media

Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] 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] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular

Dictionary 337

nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Vaccines: Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [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]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH]

338 Otitis Media

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] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

339

INDEX A Abdomen, 261, 270, 298, 301, 313, 330 Abdominal, 261, 299, 313, 335 Abdominal Pain, 261, 335 Aberrant, 49, 261 Abscess, 133, 174, 261 Acceptor, 261, 313, 334 Acetylcholine, 182, 261, 274, 310 Acetylcysteine, 141, 143, 261 Acoustic, 4, 28, 41, 47, 48, 74, 77, 114, 147, 168, 170, 171, 261, 267, 321 Acremonium, 261, 273 Acrylonitrile, 261, 325 Acuity, 261, 267 Acute renal, 261, 293 Adaptation, 59, 261 Adenine, 261, 321 Adenosine, 173, 261, 315 Adenovirus, 51, 60, 88, 117, 261 Adjustment, 261, 262 Adjuvant, 132, 154, 162, 213, 262 Adjuvant Therapy, 132, 154, 162, 262 Adolescence, 262, 273, 314 Adrenal Cortex, 262, 278, 319 Adrenergic, 262, 284, 315, 331 Adverse Effect, 15, 262, 310, 327 Aerobic, 262, 309, 313, 320 Aerosol, 189, 262, 318 Aetiology, 97, 117, 262 Afferent, 262, 287 Affinity, 184, 262, 303, 328 Agar, 97, 262, 276, 279, 295 Agenesis, 171, 262 Agonist, 262, 284, 315 Air Sacs, 262, 263 Airway, 59, 83, 95, 189, 191, 263 Algorithms, 263, 269 Alimentary, 263, 284 Alkaline, 263, 271 Alkaloid, 263, 316 Allergen, 179, 263 Allergic Rhinitis, 9, 61, 77, 141, 175, 177, 179, 190, 263 Alpha Particles, 263, 322 Alpha-Defensins, 263, 280 Alpha-helix, 263, 299 Alternative medicine, 32, 147, 156, 217, 263, 276

Aluminum, 166, 263, 338 Alveolar Process, 263, 324 Alveoli, 70, 263, 336 Amine, 222, 263, 293 Amino Acid Sequence, 84, 169, 192, 263, 265 Amino Acids, 192, 263, 285, 314, 317, 320, 325, 327, 331, 334, 335 Ammonia, 263, 331, 335 Amniotic Fluid, 264, 289 Ampicillin, 264 Anaerobic, 33, 264, 292, 308 Anaesthesia, 95, 264, 296 Anal, 27, 44, 111, 264, 284, 285, 287, 302, 307 Analgesics, 182, 264 Analog, 82, 173, 264, 275 Analogous, 81, 264, 334 Analysis of Variance, 46, 75, 264 Anaphylactic, 179, 264, 316 Anaphylatoxins, 264, 276 Anaphylaxis, 264 Anatomical, 7, 42, 49, 264, 267, 283, 295, 326 Androgens, 262, 264, 279 Anemia, 233, 264 Anesthesia, 167, 174, 206, 263, 264 Animal model, 46, 49, 53, 56, 59, 62, 69, 73, 78, 81, 264 Annealing, 264, 317 Antiallergic, 141, 265, 279 Antibacterial, 36, 130, 176, 178, 265, 274, 275, 311, 329, 331 Antibiotic Prophylaxis, 210, 265 Anticholinergic, 182, 265 Anticoagulant, 265, 320 Antifungal, 191, 265 Antigen, 62, 80, 82, 168, 262, 264, 265, 267, 276, 293, 294, 295, 296, 304 Antigen-Antibody Complex, 265, 276 Antihistamine, 24, 94, 122, 162, 175, 187, 196, 213, 244, 265 Anti-infective, 82, 265, 298 Anti-inflammatory, 35, 265, 279, 290, 313 Anti-Inflammatory Agents, 265, 279 Antineoplastic, 265, 279 Antiseptic, 179, 265, 318 Antiserum, 92, 265, 267

340 Otitis Media

Antiviral, 28, 261, 266, 297 Anus, 264, 266, 267, 270 Aphakia, 266, 324 Apolipoproteins, 266, 301 Apoptosis, 57, 266 Aqueous, 87, 190, 266, 268, 279, 283, 300 Arachidonate 12-Lipoxygenase, 266, 301 Arachidonate 15-Lipoxygenase, 266, 301 Arachidonate Lipoxygenases, 266, 301 Arachidonic Acid, 141, 144, 177, 191, 266, 283, 300, 319 Arginine, 40, 264, 266, 310 Arterial, 266, 274, 278, 290, 320 Arteries, 266, 270, 278, 302, 305, 332 Arterioles, 266, 270 Aseptic, 133, 266, 312 Aspiration, 70, 200, 206, 266 Assay, 67, 73, 80, 85, 93, 266, 269, 295 Astringents, 266, 305 Asymptomatic, 13, 24, 31, 33, 70, 266 Ataxia, 233, 267, 273, 332 Atelectasis, 27, 267 Atopic, 177, 267 Atresia, 169, 171, 267, 278 Atrium, 267, 278, 336 Atrophy, 27, 233, 267, 307 Attenuated, 267, 268, 337 Attenuation, 49, 81, 85, 267, 285 Atypical, 267, 296 Audiologist, 20, 267 Audiometry, 8, 40, 150, 267 Audition, 16, 267 Auditory nerve, 39, 267, 304 Auditory Perception, 196, 205, 267 Augmentin, 94, 267 Auricular, 166, 167, 267 Autonomic, 181, 182, 261, 267, 310, 315, 328, 331 Autonomic Nervous System, 182, 267, 315, 328, 331 Avidity, 70, 267 Azithromycin, 6, 12, 89, 90, 92, 107, 216, 217, 222, 267 B Bacteremia, 36, 50, 67, 70, 83, 153, 186, 267 Bacterial Adhesion, 82, 268 Bacterial Infections, 32, 82, 167, 176, 203, 268, 301 Bacterial Physiology, 261, 268 Bacterial Vaccines, 14, 133, 268 Bactericidal, 36, 60, 81, 88, 91, 168, 268 Bacteriophage, 268, 334

Bacteriostatic, 268, 285, 331 Bacterium, 33, 51, 85, 92, 145, 176, 268, 277, 293, 333 Barotrauma, 99, 202, 268 Basal Ganglia, 267, 268 Basal Ganglia Diseases, 267, 268 Base, 73, 123, 177, 183, 184, 261, 268, 279, 280, 299, 312, 327, 332 Basement Membrane, 268, 286, 299 Basophil, 268, 293 Benign, 172, 177, 268, 292, 309, 313, 322, 325 Beta-Defensins, 38, 268, 280 Beta-Thromboglobulin, 268, 298 Bilateral, 22, 34, 49, 86, 99, 126, 153, 162, 269, 314 Bile, 269, 288, 289, 293, 301, 329 Bile Acids, 269, 289, 329 Binaural, 45, 63, 120, 148, 205, 269 Binding Sites, 38, 56, 269 Bioassay, 269 Biochemical, 37, 38, 59, 70, 76, 269, 288, 291, 300 Biofilms, 56, 69, 78, 269 Biological Assay, 45, 269 Biological response modifier, 269, 297 Biological therapy, 269, 291 Biosynthesis, 51, 91, 116, 266, 269, 327 Biotechnology, 88, 93, 199, 217, 229, 232, 233, 234, 269 Biotype, 54, 269 Bladder, 269, 296, 320, 335, 336 Blepharospasm, 182, 269 Blood Coagulation, 269, 271, 287, 332 Blood Glucose, 270, 293 Blood pressure, 270, 290, 294, 306, 328 Blood vessel, 187, 270, 271, 278, 284, 293, 299, 302, 305, 314, 321, 327, 328, 330, 332, 336 Blood Volume, 270, 318 Blot, 73, 270 Body Fluids, 270, 271, 282, 328 Bone Conduction, 6, 267, 270 Bone Marrow, 270, 276, 291, 295, 302, 306 Bone Resorption, 39, 67, 270 Bottle Feeding, 211, 270 Bowel, 191, 264, 270, 281, 296, 298, 300, 335 Bowel Movement, 270, 281 Brachytherapy, 270, 298, 322, 337 Bradykinin, 270, 310 Brain Stem, 148, 270, 275

Index 341

Branch, 253, 270, 283, 289, 302, 304, 312, 314, 321, 328, 332 Breakdown, 89, 270, 281, 289 Breast Feeding, 20, 140, 270 Broadband, 85, 270 Broad-spectrum, 264, 270, 272, 273, 311 Bronchi, 270, 271 Bronchial, 179, 182, 193, 270, 293 Bronchioles, 263, 270, 271 Bronchiolitis, 77, 271 Bronchiseptica, 271, 315 Bronchitis, 56, 58, 181, 182, 187, 188, 193, 271, 274 Bronchoconstriction, 191, 271, 316 Bronchus, 271 Bullous, 203, 271 Bypass, 42, 271 C Calcium, 39, 177, 271, 276, 316, 327 Capsular, 64, 66, 67, 70, 83, 96, 124, 127, 271 Carbohydrate, 58, 82, 271, 279, 290, 291, 317 Carbon Dioxide, 271, 280, 288, 289, 324 Carcinogenic, 271, 297, 319, 329 Carcinogens, 271, 308, 311 Cardiac, 271, 278, 284, 308, 329 Cardiovascular, 271, 301, 328 Carotene, 271, 324 Case report, 14, 99, 101, 111, 113, 271, 275 Case series, 271, 275 Cataract, 266, 271, 324 Caudal, 272, 294, 317 Causal, 15, 26, 40, 64, 272, 285, 326, 332 Causality, 15, 40, 272 Cause of Death, 79, 181, 187, 188, 272 Cefaclor, 89, 108, 122, 272 Ceftriaxone, 8, 26, 90, 105, 215, 272 Cefuroxime, 8, 26, 91, 272 Cell Death, 266, 272, 309 Cell Differentiation, 272, 327 Cell Division, 70, 233, 268, 272, 291, 304, 306, 316, 319, 326 Cell Extracts, 71, 272 Cell membrane, 272, 280, 286, 315 Cell proliferation, 76, 272, 327 Cell Size, 272, 288 Cell Survival, 272, 291 Cellulitis, 155, 182, 272 Cellulose, 272, 288, 305, 316 Central Nervous System, 16, 261, 267, 273, 274, 284, 288, 290, 292, 301, 317

Cephalexin, 272, 273 Cephalosporins, 6, 12, 217, 222, 273 Cerebellar, 267, 273, 323, 335 Cerebellar Diseases, 267, 273, 335 Cerebral, 267, 268, 270, 273, 286, 287, 321, 328 Cerebral hemispheres, 268, 270, 273 Cerebral Palsy, 273, 328 Cerebrum, 273, 335 Cerumen, 4, 19, 273 Cervical, 273, 325, 333 Character, 85, 273, 280 Chemotactic Factors, 273, 276 Chemotherapy, 107, 116, 122, 210, 262, 273 Child Care, 17, 20, 22, 209, 273 Child Development, 15, 198, 200, 273 Child Language, 75, 273 Chiropractic, 147, 156, 238, 273 Chlorophyll, 273, 288 Cholera, 273, 327 Cholesteatoma, 5, 7, 27, 30, 38, 39, 67, 108, 169, 171, 174, 201, 239, 274 Cholesterol, 101, 211, 269, 274, 301, 302, 329 Cholesterol Esters, 274, 301 Choline, 70, 274 Cholinergic, 182, 274 Chromatin, 266, 274 Chromosomal, 18, 274, 316 Chromosome, 54, 274, 277, 292, 301, 326 Chronic Disease, 175, 274 Chronic Obstructive Pulmonary Disease, 62, 83, 84, 181, 187, 188, 191, 274 Chronic renal, 274, 317 Chylomicrons, 274, 301 Ciliary, 58, 106, 173, 180, 181, 187, 274, 307 Ciprofloxacin, 108, 274 Circumcision, 174, 274 CIS, 177, 274, 324 Clarithromycin, 12, 90, 99, 121, 222, 274 Clavulanic Acid, 95, 122, 274 Cleft Palate, 17, 48, 130, 150, 202, 210, 275 Clindamycin, 14, 275 Clinical Medicine, 97, 140, 275, 318 Clinical study, 85, 200, 275 Clonic, 269, 275 Cloning, 38, 73, 85, 269, 275 Cochlea, 275, 297, 325, 329, 335 Cochlear, 16, 41, 63, 101, 102, 275, 333, 336 Cochlear Implantation, 16, 275 Cochlear Nerve, 275, 336 Cod Liver Oil, 120, 142, 151, 275, 283

342 Otitis Media

Cofactor, 275, 310, 320, 332 Cognition, 15, 40, 72, 119, 196, 275, 300 Cohort Studies, 44, 275, 285 Colitis, 177, 182, 191, 275, 296, 335 Collagen, 268, 275, 286, 287, 316 Colloidal, 275, 283, 286 Colony-Stimulating Factors, 28, 275, 291 Communication Disorders, 52, 81, 161, 162, 164, 228, 239, 240, 241, 243, 245, 276 Complement, 36, 67, 70, 81, 264, 276, 289, 303 Complementary and alternative medicine, 32, 147, 156, 276 Complementary medicine, 147, 276 Computational Biology, 229, 232, 276 Computed tomography, 276, 277 Computer Simulation, 86, 277 Computer Systems, 53, 277 Computerized axial tomography, 276, 277 Computerized tomography, 132, 276, 277 Concomitant, 42, 277 Conduction, 6, 267, 270, 277 Cones, 277, 324 Congestion, 42, 174, 182, 186, 187, 193, 257, 277, 280, 285 Conjugated, 29, 89, 106, 167, 277 Conjugation, 78, 168, 277 Conjunctiva, 277, 297 Conjunctivitis, 179, 190, 277 Conjunctivitis, Allergic, 179, 277 Connective Tissue, 270, 272, 275, 277, 287, 288, 290, 302, 305, 325 Consciousness, 264, 277, 282 Consultation, 22, 277 Consumption, 176, 277, 281, 324 Contact dermatitis, 179, 277 Contamination, 69, 278 Continuum, 76, 278 Contraindications, ii, 278 Contralateral, 6, 75, 278, 323 Control group, 72, 278, 322 Conventional therapy, 154, 278 Conventional treatment, 278 Convulsion, 269, 278 Coordination, 84, 278 Cor, 278, 290 Coronary, 278, 305 Coronary Thrombosis, 278, 305 Coronavirus, 103, 278 Cortex, 179, 262, 267, 278, 286, 287, 319, 323, 333 Corticosteroid, 94, 122, 162, 175, 278, 330

Cranial, 267, 275, 279, 286, 287, 292, 313, 315, 329, 336 Crossing-over, 279, 323 Cross-Sectional Studies, 47, 279, 285 Cryptosporidiosis, 267, 279 Cues, 45, 77, 279 Culture Media, 262, 279 Curative, 58, 279, 332 Custom-made, 72, 279 Cutaneous, 277, 279, 299 Cyclic, 279, 291, 310, 319 Cyst, 174, 279 Cysteine, 178, 261, 279, 280, 331 Cystine, 279 Cytidine, 173, 181, 279 Cytidine Triphosphate, 173, 279 Cytokine, 61, 62, 64, 68, 90, 91, 279, 298 Cytoplasm, 266, 272, 279, 284, 291, 306, 325 Cytosine, 279, 280 Cytotoxic, 280, 322, 327 D Data Collection, 44, 73, 87, 280 Databases, Bibliographic, 229, 280 Day Care, 8, 13, 17, 19, 22, 25, 31, 173, 207, 280 Decarboxylation, 280, 293 Decision Making, 53, 104, 280 Decongestant, 24, 175, 184, 187, 196, 244, 280 Defense Mechanisms, 49, 280 Defensins, 38, 194, 263, 268, 280 Degenerative, 280, 293, 324 Deletion, 18, 266, 280 Delivery of Health Care, 280, 292 Denaturation, 280, 317 Dendrites, 280, 310 Density, 57, 114, 141, 280, 288, 301, 302, 311, 317, 328 Dental Caries, 31, 172, 176, 280, 328 Depolarization, 280, 327 Deprivation, 33, 281 Dermatitis, 179, 277, 281, 282 Developed Countries, 179, 281 Developing Countries, 35, 62, 67, 281 Dextrorotatory, 184, 281 Diabetes Mellitus, 281, 293, 297 Diagnostic procedure, 25, 165, 217, 281 Diarrhea, 62, 155, 182, 256, 279, 281 Diffusion, 281, 295, 296 Digestion, 263, 269, 270, 281, 298, 301, 313, 330

Index 343

Digestive system, 164, 281, 307 Dihydrotestosterone, 281, 323 Dilatation, 281, 318 Dilation, 42, 270, 281 Diphtheria, 17, 66, 281 Diploid, 281, 316 Direct, iii, 5, 36, 66, 79, 82, 179, 180, 184, 221, 275, 281, 313, 315, 323 Discrimination, 41, 48, 267, 281 Disease Progression, 42, 45, 49, 281 Dissociation, 262, 281 Distal, 85, 282, 289, 320 Diuretic, 282, 303, 328 Dizziness, 167, 174, 211, 256, 282, 336 Dorsal, 282, 317 Drug Interactions, 223, 282 Drug Resistance, 12, 29, 282 Drug Tolerance, 282, 333 Duct, 187, 282, 286, 326, 331 Duodenum, 269, 282, 313, 330 Dura mater, 282, 305, 313 Dyskinesia, 58, 181, 188, 282 Dysostosis, 282, 304 Dysphonia, 182, 282 Dysplasia, 233, 282 Dystrophy, 233, 282, 308 E Ear Diseases, 8, 173, 282 Earache, 211, 218, 242, 256, 282 Eardrum, 4, 5, 19, 24, 178, 201, 207, 211, 239, 282 Echinacea, 32, 282 Eczema, 177, 191, 282 Edema, 277, 282, 299, 308, 309 Effector, 261, 276, 282 Eicosanoids, 191, 283 Elasticity, 142, 149, 283 Elastin, 275, 283, 286 Electrolyte, 279, 283, 306, 328 Electrons, 268, 283, 298, 313, 322 Electrophoresis, 54, 59, 283, 295 Electrophysiological, 41, 77, 283 Embryo, 272, 283, 296 Emphysema, 182, 193, 274, 283 Empiric, 8, 20, 26, 283 Empirical, 20, 25, 283 Empyema, 174, 283 Emulsion, 283, 288 Enamel, 280, 283, 299 Encephalitis, 283, 284 Encephalomyelitis, 62, 283 Endocarditis, 56, 284

Endocardium, 284 Endocrine Glands, 284 Endothelial cell, 62, 284, 298, 332 Endothelium, 284, 310 Endothelium-derived, 284, 310 Endotoxin, 106, 115, 144, 153, 284, 335 End-stage renal, 274, 284, 317 Enhancer, 284, 324 Enteral Nutrition, 180, 284 Environmental Exposure, 284, 311 Environmental Health, 228, 230, 284 Environmental tobacco smoke, 7, 284 Enzymatic, 183, 271, 276, 280, 284, 293, 317, 324 Eosinophil, 191, 284, 291 Eosinophilic, 103, 284 Ephedrine, 182, 284 Epidemic, 62, 284, 329 Epidemiologic Factors, 27, 54, 285 Epidemiologic Studies, 203, 285 Epidemiological, 7, 35, 64, 143, 152, 285 Epidermal, 108, 285, 299, 304 Epidermal Growth Factor, 108, 285 Epidermis, 285, 299 Epithelial Cells, 28, 36, 56, 57, 59, 62, 64, 68, 70, 76, 83, 84, 85, 180, 268, 285, 297, 299 Epithelium, 38, 57, 59, 64, 68, 141, 180, 268, 274, 284, 285, 324, 329 Epitope, 53, 63, 186, 192, 285 Equalization, 189, 285 Erythema, 19, 256, 277, 285, 336 Erythrocytes, 264, 270, 285, 323 Erythromycin, 14, 200, 222, 267, 274, 285 Esophagus, 267, 281, 285, 289, 302, 315, 323, 329, 330 Esotropia, 285, 330 Essential Tremor, 233, 285 Ethmoid, 286, 313 Eukaryotic Cells, 55, 57, 286, 296, 312 Evoke, 286, 330 Excipient, 183, 184, 286 Excitation, 286, 288 Exocrine, 193, 286, 313 Exocytosis, 286, 293 Exogenous, 282, 286 Exotropia, 286, 330 Expander, 286, 318 Expiration, 69, 286, 324 Extensor, 286, 321 External-beam radiation, 286, 298, 322, 337

344 Otitis Media

Extracellular, 56, 58, 144, 269, 277, 286, 287, 328 Extracellular Matrix, 56, 277, 286, 287 Extracellular Matrix Proteins, 56, 286 Extracellular Space, 286 Extraction, 190, 266, 286, 324 Eye Infections, 261, 287 F Facial, 10, 17, 94, 109, 124, 126, 133, 166, 287, 290, 304, 328 Facial Nerve, 94, 124, 126, 166, 287, 290 Facial Paralysis, 10, 133, 287 Family Planning, 229, 287 Family Practice, 54, 95, 96, 104, 115, 125, 136, 137, 152, 287 Fat, 266, 270, 271, 278, 279, 287, 290, 301, 325, 328, 331 Fathers, 75, 287 Fatty acids, 167, 177, 189, 283, 287, 290, 301, 319, 333 Febrile, 186, 287 Fibroblasts, 38, 287, 298 Fibronectins, 286, 287 Fibrosis, 38, 69, 85, 181, 182, 187, 188, 193, 233, 287, 326 Fissure, 275, 287 Fistula, 119, 287 Fixation, 169, 171, 287 Flatus, 288, 289 Flow Cytometry, 49, 288 Fluorescence, 18, 45, 52, 288 Fluorescent Dyes, 288 Fold, 52, 57, 67, 195, 287, 288, 318 Fossa, 101, 288 Fovea, 288 Fructose, 185, 288, 290, 298 Fungi, 265, 277, 287, 288, 305, 338 Fungus, 191, 192, 273, 288 G Gallbladder, 261, 281, 288 Gamma Rays, 288, 322 Ganglia, 261, 267, 268, 288, 309, 315, 331 Gangrenous, 288, 327 Gas, 28, 34, 37, 40, 42, 46, 75, 99, 112, 166, 263, 271, 281, 288, 289, 294, 297, 308, 309, 310, 321, 324, 336 Gas exchange, 42, 112, 289, 324, 336 Gastric, 118, 264, 285, 289, 293 Gastric Acid, 264, 289 Gastroesophageal Reflux, 96, 289 Gastrointestinal, 87, 270, 274, 278, 284, 289, 301, 328, 330

Gastrointestinal tract, 289, 301 Gastrostomy, 284, 289 Gene Expression, 33, 68, 70, 76, 78, 83, 91, 103, 122, 234, 289 Gene Library, 289 General practitioner, 14, 289 Genetic Engineering, 269, 275, 289 Genetic testing, 289, 317 Genetics, 47, 51, 79, 81, 114, 216, 277, 289 Genital, 274, 289 Genomic Library, 103, 289 Genomics, 52, 289 Genotype, 54, 61, 269, 289, 315 Gestational, 22, 29, 289 Gestational Age, 22, 29, 289 Gland, 112, 262, 278, 289, 290, 302, 304, 313, 316, 320, 326, 330, 331, 333 Glomerular, 290, 298, 303 Glomerular Filtration Rate, 290, 303 Glomeruli, 290, 321 Glossopalatine, 290, 313 Glottis, 290, 315 Glucocorticoids, 83, 262, 279, 290 Gluconeogenesis, 290 Glucose, 233, 270, 272, 281, 290, 293, 297, 326, 328 Glutamate, 68, 290 Glycerol, 290, 315 Glycerophospholipids, 290, 315 Glycine, 290, 327 Glycogen, 290 Glycoprotein, 290, 291, 299, 303, 307, 332, 335 Glycosaminoglycans, 286, 290 Glycoside, 290, 294, 326 Glycosidic, 290, 309, 311 Glycosylation, 70, 291 Goats, 291, 324 Goblet Cells, 117, 291 Gonadal, 291, 329 Gonorrhea, 272, 291 Governing Board, 291, 318 Graft, 21, 291, 294 Grafting, 291, 295 Gram-negative, 51, 78, 176, 180, 271, 272, 273, 291, 292, 308, 309, 311, 320 Gram-positive, 50, 176, 272, 273, 291, 307, 311, 330, 331 Granule, 49, 291, 325 Granulocyte Colony-Stimulating Factor, 276, 291

Index 345

Granulocyte-Macrophage ColonyStimulating Factor, 276, 291 Granulocytes, 268, 276, 291, 300, 327, 337 Granuloma, 101, 112, 211, 291 Growth, 8, 16, 27, 31, 40, 55, 65, 69, 108, 173, 174, 176, 180, 185, 201, 233, 262, 264, 265, 266, 268, 272, 273, 279, 281, 285, 291, 297, 303, 309, 311, 312, 316, 317, 333 Growth factors, 40, 69, 291 Guanylate Cyclase, 291, 310 H Habitat, 292, 310 Habitual, 24, 273, 292 Half-Life, 13, 272, 292 Hammer, 166, 292 Haploid, 292, 316 Haplotypes, 63, 292 Haptens, 262, 292 Headache, 256, 292, 297 Health Care Costs, 8, 51, 64, 292 Health Education, 210, 292 Health Expenditures, 292 Health Services, iv, 32, 35, 231, 280, 292 Hearing aid, 23, 113, 292 Hearing Disorders, 238, 276, 292 Heart failure, 284, 292 Heme, 55, 93, 292 Hemin, 65, 292 Hemoglobin, 55, 65, 264, 285, 292, 293 Hemoglobin A, 55, 293 Hemoglobinuria, 233, 293 Hemolytic, 107, 293 Hemorrhage, 292, 293, 330 Hepatitis, 293, 296 Hepatobiliary, 293, 316 Hepatomegaly, 293, 296 Hereditary, 20, 293, 325 Heredity, 289, 293 Heritability, 7, 59, 61, 113, 293 Heterogeneity, 81, 262, 293 Heterotropia, 293, 330 Histamine, 61, 66, 122, 190, 264, 265, 293 Histamine Release, 61, 264, 293 Histidine, 293 Histology, 49, 293, 313 Homogeneous, 278, 293 Homologous, 55, 81, 103, 279, 293, 307, 326, 331 Hormonal, 267, 269, 279, 294 Hormone, 262, 269, 278, 283, 294, 297, 298, 304, 318, 325, 327, 332, 333

Hormone therapy, 262, 294 Hybrid, 294 Hybridization, 18, 39, 45, 54, 64, 73, 294, 296, 311 Hybridomas, 294, 298 Hydration, 181, 187, 294 Hydrogen, 261, 263, 268, 271, 280, 286, 294, 306, 310, 311, 312, 320 Hydrolases, 58, 294, 303, 314, 315 Hydrolysis, 294, 309, 314, 315, 317, 320 Hydrophobic, 290, 294, 301 Hyperaemia, 277, 294 Hyperplasia, 69, 294 Hypersensitivity, 28, 29, 62, 179, 263, 264, 277, 284, 294, 301, 325 Hypertrophy, 278, 294 Hypoplasia, 48, 294 Hypotension, 294, 316 Hypothalamus, 267, 294, 316 I Id, 145, 154, 239, 244, 245, 246, 252, 254, 294 Immaturity, 48, 295 Immune function, 57, 295 Immune Sera, 295 Immune system, 21, 60, 62, 187, 269, 295, 301, 302, 303, 336, 337 Immunity, 25, 36, 38, 51, 55, 62, 65, 67, 116, 169, 183, 186, 280, 295, 334 Immunization, 35, 44, 51, 55, 60, 62, 63, 66, 82, 88, 91, 92, 295, 318 Immunoassay, 73, 295 Immunocompromised, 124, 295 Immunodeficiency, 62, 233, 295 Immunodiffusion, 262, 295 Immunoelectrophoresis, 262, 295 Immunogen, 193, 295 Immunogenic, 35, 60, 167, 192, 295 Immunoglobulin, 28, 61, 70, 115, 265, 295, 306 Immunohistochemistry, 73, 295 Immunologic, 17, 21, 68, 116, 273, 289, 295, 322 Immunology, 21, 33, 50, 52, 73, 79, 175, 262, 288, 295 Implant radiation, 295, 298, 322, 337 Implantation, 16, 102, 275, 295 In situ, 38, 64, 73, 296 In Situ Hybridization, 38, 64, 73, 296 In vivo, 33, 36, 38, 40, 42, 45, 49, 53, 62, 67, 71, 76, 79, 84, 91, 185, 269, 296, 307, 332 Incision, 184, 296, 298

346 Otitis Media

Incompetence, 289, 296 Incontinence, 284, 296 Incubation, 296, 315 Incubation period, 296, 315 Incus, 296, 329 Indicative, 197, 296, 314, 336 Induction, 45, 52, 70, 81, 85, 117, 181, 187, 264, 296 Infancy, 9, 15, 22, 24, 63, 73, 136, 296 Infarction, 268, 278, 296, 305 Infectious Mononucleosis, 100, 140, 296, 307 Infiltration, 71, 296 Inflammatory bowel disease, 191, 296 Influenza, 28, 30, 60, 61, 64, 78, 82, 89, 106, 107, 118, 214, 255, 297 Ingestion, 297, 317 Inhalation, 262, 297, 317 Initiation, 163, 297, 319, 334 Initiator, 37, 269, 297 Inlay, 297, 324 Inner ear, 38, 58, 67, 74, 85, 166, 173, 186, 210, 270, 272, 297, 299 Innervation, 287, 297 Inorganic, 297, 307, 328 Insight, 33, 51, 56, 65, 68, 82, 86, 297 Insufflation, 20, 297 Insulin, 269, 297 Interferon, 61, 297 Interferon-alpha, 297 Interleukin-1, 38, 108, 132, 297 Interleukin-2, 297 Interleukin-3, 276, 297 Interleukin-6, 68, 297 Interleukin-8, 68, 298 Intermittent, 42, 126, 298 Internal radiation, 298, 322, 337 Interstitial, 270, 286, 298, 337 Intestinal, 263, 271, 279, 298, 303 Intestine, 270, 282, 294, 298, 300, 308, 323, 330 Intracellular, 69, 71, 80, 85, 296, 298, 303, 304, 310, 319, 327 Intracellular Membranes, 298, 304 Intramuscular, 8, 26, 51, 105, 298 Intramuscular injection, 51, 298 Intrinsic, 4, 22, 25, 262, 268, 298 Introns, 289, 298 Inulin, 282, 290, 298 Invasive, 33, 34, 35, 50, 53, 55, 64, 66, 70, 84, 186, 191, 192, 295, 298, 303

Involuntary, 268, 278, 284, 285, 298, 308, 323, 327, 328, 333 Iodine, 108, 298, 318 Ions, 268, 281, 283, 294, 298 Ipsilateral, 75, 298, 323 Irradiation, 110, 298, 337 Irritants, 57, 186, 299 Ischemia, 267, 299 J Jejunostomy, 284, 299 Joint, 75, 95, 256, 274, 299, 331 K Kb, 228, 299 Keratin, 174, 299 Keratinocytes, 298, 299 Keratolytic, 280, 299 Kidney Disease, 164, 228, 233, 299 Kidney Failure, 284, 299, 303 L Labile, 276, 299 Labyrinth, 275, 297, 299, 312, 326, 336 Labyrinthitis, 10, 119, 299 Laceration, 299, 332 Lacrimal, 287, 290, 299, 308, 312 Lacrimal Apparatus, 299, 308 Lactoperoxidase, 172, 299 Laminin, 268, 286, 299 Language Development, 3, 19, 41, 48, 75, 196, 202, 218, 242, 243, 300 Language Development Disorders, 300 Language Disorders, 25, 243, 276, 300 Language Therapy, 210, 300 Large Intestine, 281, 298, 300, 323 Laryngeal, 96, 300 Larynx, 109, 121, 126, 141, 142, 145, 290, 300 Latency, 48, 300 Latent, 178, 300, 318 Laxative, 262, 300, 305, 328 Least-Squares Analysis, 300, 323 Lectin, 119, 300, 304 Lens, 266, 271, 300, 324, 337 Lesion, 67, 131, 201, 291, 300, 301, 327, 335 Lethal, 268, 300, 308 Leucocyte, 284, 300 Leukemia, 233, 300 Leukocytes, 64, 270, 273, 291, 297, 300, 306, 335 Leukotrienes, 142, 144, 191, 266, 283, 300 Levofloxacin, 162, 163, 301 Library Services, 252, 301 Ligament, 301, 320

Index 347

Ligands, 36, 55, 301 Likelihood Functions, 301, 323 Lincomycin, 275, 301 Linear Models, 301, 323 Linkages, 72, 290, 293, 301, 309, 332 Lip, 48, 130, 210, 301 Lipid, 38, 76, 168, 189, 266, 274, 290, 297, 301 Lipopolysaccharide, 53, 115, 291, 301 Lipoprotein, 62, 92, 186, 291, 301, 302 Lipoxygenase, 191, 266, 301 Liver, 120, 142, 151, 261, 266, 269, 275, 281, 283, 288, 290, 291, 293, 301, 335 Localization, 55, 295, 301 Localized, 56, 167, 280, 281, 287, 296, 299, 301, 316, 332, 335, 336 Locomotion, 301, 316 Logistic Models, 302, 323 Longitudinal Studies, 47, 72, 279, 302 Longitudinal study, 75, 113, 302 Loop, 60, 302 Low-density lipoprotein, 301, 302 Lower Esophageal Sphincter, 289, 302 Luciferase, 85, 302 Lumen, 189, 302 Lymph, 273, 284, 296, 302, 325, 330 Lymph node, 273, 302, 325 Lymphadenopathy, 296, 302 Lymphatic, 284, 296, 302, 305, 325, 333 Lymphatic system, 302, 325, 333 Lymphocyte, 121, 265, 302, 303, 304 Lymphoid, 100, 265, 300, 303, 333 Lymphoma, 233, 303 Lysosomal Storage Diseases, 58, 303 M Macrolides, 12, 303 Macrophage, 56, 93, 276, 291, 297, 303 Macrophage Colony-Stimulating Factor, 276, 291, 303 Magnetic Resonance Imaging, 49, 303 Major Histocompatibility Complex, 292, 303 Malabsorption, 233, 303 Malformation, 58, 303 Malignancy, 96, 303 Malignant, 233, 265, 303, 309, 322 Malnutrition, 267, 303, 307 Mandible, 263, 303, 324 Manifest, 175, 178, 303, 330 Mannans, 288, 303 Mannitol, 176, 303 Mannosidosis, 113, 303

Mass Screening, 171, 304 Mastitis, 304, 327 Mastoiditis, 5, 10, 18, 99, 112, 123, 174, 203, 204, 211, 304 Maxillary, 304, 313 Measles Virus, 62, 304 Meatus, 282, 304, 312, 335 Mechanical ventilation, 8, 304 Medial, 286, 304, 312, 325, 329 Mediate, 28, 47, 55, 64, 68, 70, 82, 275, 304 Mediator, 66, 188, 297, 304, 316 Medical Records, 20, 304, 325 Medicament, 184, 304 MEDLINE, 21, 229, 232, 233, 304 Meiosis, 304, 307, 331 Melanocytes, 304 Melanoma, 233, 304 Membrane Proteins, 50, 60, 81, 85, 168, 193, 304 Memory, 48, 158, 202, 304 Meninges, 272, 273, 274, 282, 305 Meningitis, 6, 18, 36, 50, 53, 56, 64, 70, 82, 83, 93, 99, 112, 133, 143, 155, 174, 180, 186, 305, 309 Meningococcal Infections, 81, 305 Mental Disorders, 164, 300, 305, 318, 321 Mental Health, iv, 32, 164, 228, 231, 305, 318, 321 Mental Retardation, 234, 276, 305 Mentors, 38, 305 Mercury, 179, 288, 305 Mesenchymal, 285, 291, 303, 305 Meta-Analysis, 3, 21, 135, 305 Metaplasia, 76, 117, 305 Methylcellulose, 144, 305 MI, 258, 305 Microbe, 56, 305, 334 Microbiological, 142, 143, 150, 152, 305 Microorganism, 275, 305, 314, 337 Micro-organism, 185, 280, 305, 326 Microscopy, 73, 82, 268, 306 Middle Ear Ventilation, 205, 306 Migration, 16, 93, 191, 306 Mineralocorticoids, 262, 279, 306 Mitochondrial Swelling, 306, 309 Mitosis, 266, 306 Mobility, 4, 5, 85, 306 Modeling, 38, 47, 73, 114, 306 Modification, 39, 53, 285, 289, 306, 321 Molecular mass, 65, 306 Monitor, 79, 306, 310

348 Otitis Media

Monoclonal, 67, 91, 172, 294, 298, 306, 322, 337 Monoclonal antibodies, 67, 306 Monocytes, 62, 297, 298, 300, 306, 307, 316 Mononuclear, 291, 296, 303, 306, 335 Mononucleosis, 100, 140, 296, 306 Morbillivirus, 304, 307 Morphological, 283, 288, 304, 307 Morphology, 49, 68, 205, 271, 307 Motion Sickness, 307, 308 Motor nerve, 182, 307 Mouth Breathing, 22, 307 Mucins, 76, 181, 187, 291, 307, 326 Mucociliary, 28, 57, 58, 173, 181, 187, 307, 327 Mucociliary Clearance, 28, 57, 58, 181, 187, 307 Mucolytic, 261, 307 Mucosa, 53, 56, 57, 69, 76, 100, 135, 141, 144, 175, 297, 307, 308, 324, 330 Mucositis, 128, 191, 192, 193, 307 Mucus, 76, 85, 181, 183, 184, 187, 188, 191, 193, 307, 325, 335 Multivalent, 186, 267, 307 Multivariate Analysis, 75, 110, 307 Mupirocin, 176, 307 Muscle Fibers, 307 Muscular Atrophy, 233, 307 Muscular Diseases, 287, 307 Muscular Dystrophies, 282, 308 Musculature, 43, 308 Mustard Gas, 299, 308 Mutagenesis, 45, 52, 59, 85, 308 Mutagens, 308 Myalgia, 297, 308 Mycoplasma, 36, 308 Mydriatic, 281, 308 Myocarditis, 281, 308 Myocardium, 305, 308 Myopia, 308, 323, 324 Myotonic Dystrophy, 233, 308 N Narcolepsy, 284, 308 Nasal Cavity, 182, 192, 308, 313 Nasal Mucosa, 180, 297, 308 Nasal Septum, 308 Nasogastric, 284, 308 Nasolacrimal, 187, 308 Nasopharyngitis, 180, 308 Nasopharynx, 28, 33, 81, 84, 97, 176, 177, 180, 182, 186, 190, 308, 309 Nausea, 182, 257, 308

NCI, 1, 163, 227, 274, 309 Necrosis, 64, 66, 68, 91, 108, 117, 132, 266, 296, 305, 309, 335 Neisseria, 51, 180, 291, 305, 309 Neisseria meningitidis, 305, 309 Neodymium, 166, 309 Neon, 166, 309 Neonatal, 63, 111, 186, 190, 309 Neonatal period, 63, 309 Neoplasia, 233, 309 Neoplasm, 309, 313 Neoplastic, 274, 294, 303, 309 Nephropathy, 299, 309 Nephrosis, 309 Nephrotic, 177, 309 Nephrotic Syndrome, 177, 309 Networks, 69, 309 Neural, 28, 48, 262, 309, 324 Neuraminidase, 82, 90, 141, 307, 309 Neurologic, 21, 196, 244, 310 Neuromuscular, 48, 182, 261, 287, 310 Neuromuscular Junction, 182, 261, 310 Neuronal, 68, 310 Neurons, 40, 68, 275, 280, 288, 310, 331, 337 Neutrons, 263, 298, 310, 322 Neutropenia, 310, 316 Neutrophil, 49, 131, 310 Niche, 55, 310 Nickel, 179, 310 Nitric Oxide, 38, 40, 68, 310 Nitrite Reductases, 33, 310 Nitrogen, 263, 264, 286, 288, 306, 310, 313 Noel, 76, 310 Nonverbal Communication, 276, 310 Norepinephrine, 262, 284, 310, 315 Nuclear, 83, 128, 268, 277, 283, 286, 288, 309, 310 Nuclei, 263, 275, 277, 283, 287, 289, 298, 303, 306, 310, 311, 320, 325, 337 Nucleic acid, 280, 294, 296, 308, 310, 311, 321 Nucleic Acid Hybridization, 294, 311 Nucleotidases, 294, 311 Nucleus, 266, 267, 268, 274, 275, 279, 286, 288, 290, 304, 306, 310, 311, 319, 320, 323, 328, 330, 332, 337 Nurse Practitioners, 12, 157, 311 O Oculi, 269, 311 Odds Ratio, 21, 311

Index 349

Office Visits, 12, 13, 17, 51, 169, 173, 192, 195, 311 Ofloxacin, 144, 311 Ointments, 311, 313 Oligosaccharides, 17, 183, 309, 311 Oliguria, 299, 303, 311 Oncogene, 233, 311 Opacity, 89, 271, 280, 311 Operon, 49, 311, 319, 323 Ophthalmology, 288, 311, 324 Opsin, 311, 324 Orbicularis, 269, 312 Orderly, 74, 312 Organ Culture, 39, 312 Organelles, 279, 304, 306, 312 Osmolarity, 303, 312 Osmosis, 312 Osmotic, 76, 306, 312 Ossicle, 58, 312 Osteoclasts, 38, 40, 68, 312 Otolaryngologist, 9, 10, 20, 27, 167, 201, 202, 203, 312 Otorrhea, 34, 78, 86, 174, 201, 257, 312 Otosclerosis, 169, 171, 312 Outer ear, 167, 312 Outpatient, 12, 16, 77, 162, 312 Oval Window, 166, 312 Oxidation, 191, 261, 266, 279, 312 Oxidative metabolism, 301, 313 P Pachymeningitis, 305, 313 Paediatric, 95, 130, 313 Palatal Muscles, 48, 313 Palate, 18, 48, 130, 150, 202, 210, 275, 308, 313, 328, 333, 336 Palliative, 313, 332 Palsy, 109, 124, 126, 273, 313, 328 Pancreas, 261, 281, 297, 313 Pancreatic, 193, 233, 289, 313 Pancreatic cancer, 233, 313 Pancreatic Insufficiency, 193, 313 Pancreatic Juice, 289, 313 Papilloma, 171, 313 Paraffin, 177, 313 Paralysis, 10, 94, 109, 133, 257, 285, 287, 313, 314, 328 Paranasal Sinuses, 175, 181, 192, 313, 327 Parasite, 313 Parasitic, 60, 239, 279, 313 Parasitic Diseases, 60, 239, 313 Paresis, 287, 313 Paroxysmal, 233, 314, 315, 337

Particle, 314, 328, 334 Pathogen, 6, 19, 36, 38, 51, 52, 57, 60, 70, 78, 81, 84, 85, 89, 188, 193, 296, 314 Pathologic, 171, 203, 266, 278, 294, 314, 321, 324 Pathologic Processes, 266, 314 Pathologies, 168, 170, 171, 314 Pathophysiology, 14, 25, 68, 201, 314 Patient Education, 218, 240, 243, 250, 252, 258, 314 Patient Selection, 204, 314 Pelvic, 314, 320 Penicillin, 6, 14, 64, 90, 91, 92, 93, 99, 112, 123, 126, 264, 314 Penicillin Resistance, 91, 314 Peptide, 36, 192, 274, 294, 299, 314, 317, 320 Peptide Chain Elongation, 274, 314 Peptide Hydrolases, 294, 314 Perception, 4, 74, 77, 153, 158, 196, 204, 205, 267, 292, 314, 329 Perceptual Masking, 131, 314 Perennial, 190, 282, 314, 335 Perforation, 5, 9, 27, 169, 171, 174, 201, 239, 314 Perfusion, 25, 314 Peripheral blood, 63, 297, 315 Peripheral Nervous System, 313, 315, 330 Pertussis, 17, 99, 315, 337 Petroleum, 313, 315 Phagocytosis, 56, 67, 315 Phallic, 287, 315 Pharmacodynamic, 93, 315 Pharmacologic, 68, 189, 206, 264, 292, 315, 334 Pharyngitis, 133, 315 Pharynx, 289, 297, 308, 315, 333 Phenotype, 36, 40, 47, 61, 68, 89, 315 Phenylpropanolamine, 183, 184, 315 Phospholipases, 315, 327 Phospholipids, 189, 287, 301, 315 Phosphoric Monoester Hydrolases, 294, 315 Phosphorus, 271, 315 Phosphorylated, 185, 316 Phosphorylcholine, 36, 53, 316 Physical Examination, 19, 289, 316 Physiologic, 17, 20, 25, 41, 63, 262, 269, 292, 298, 316, 319, 322, 324, 335 Physiology, 206, 243, 261, 268, 283, 316, 324, 336 Pigment, 304, 311, 316, 324

350 Otitis Media

Pilot study, 81, 87, 316 Piperidines, 190, 191, 316 Pituitary Gland, 278, 316 Plants, 190, 263, 271, 274, 280, 290, 298, 300, 307, 310, 316, 320, 326, 334, 335 Plasma, 62, 265, 268, 270, 272, 274, 276, 286, 287, 290, 293, 299, 306, 308, 316, 323, 326 Plasma cells, 265, 316 Plasmid, 51, 188, 316, 336 Platelet Activating Factor, 36, 142, 316 Platelet Activation, 316, 327 Platelet Aggregation, 264, 310, 316, 332 Platelet Factor 4, 298, 316 Platelets, 266, 268, 310, 316, 332, 333 Platinum, 179, 302, 317 Pleated, 299, 317 Pneumococcal Infections, 11, 64, 70, 317 Poisoning, 190, 199, 305, 308, 317, 326 Polycystic, 233, 317 Polyethylene, 177, 179, 317 Polymerase, 13, 64, 103, 117, 123, 317, 319, 323, 325 Polymerase Chain Reaction, 13, 64, 103, 117, 123, 317, 325 Polymers, 82, 269, 317, 320, 330 Polymorphism, 112, 317 Polyp, 114, 317 Polypeptide, 263, 275, 285, 294, 317, 320, 338 Polysaccharide, 35, 50, 64, 66, 67, 70, 106, 127, 265, 272, 317, 320 Pons, 270, 287, 317 Posterior, 201, 264, 267, 282, 290, 312, 313, 317, 329, 333, 336 Postoperative, 30, 34, 244, 317 Postsynaptic, 317, 327 Potentiate, 184, 317 Potentiating, 269, 318 Potentiation, 318, 327 Povidone, 108, 318 Povidone-Iodine, 108, 318 Practicability, 318, 335 Practice Guidelines, 23, 34, 53, 196, 231, 244, 318 Precipitating Factors, 272, 318 Preclinical, 15, 318 Precursor, 56, 266, 274, 282, 284, 291, 310, 318, 335 Predisposition, 8, 318 Pregnancy Tests, 289, 318 Prepuce, 274, 318

Primary Prevention, 17, 318 Private Sector, 21, 318 Probe, 23, 45, 52, 74, 167, 170, 318 Progeny, 277, 318 Progesterone, 318, 329 Prognostic factor, 26, 319 Progression, 6, 14, 38, 42, 45, 49, 58, 264, 281, 319 Progressive, 38, 58, 67, 167, 181, 272, 274, 282, 291, 308, 309, 316, 319 Projection, 280, 310, 319, 323 Promoter, 37, 45, 52, 61, 85, 319 Promotor, 319, 324 Prone, 8, 13, 17, 64, 180, 319 Prophase, 307, 319, 331 Prophylaxis, 12, 27, 64, 126, 137, 210, 265, 319, 336 Prospective Studies, 3, 15, 72, 319 Prospective study, 15, 22, 61, 302, 319 Prostaglandin, 141, 319, 332 Prostaglandins A, 319 Prostate, 233, 320 Prostatitis, 70, 320 Prosthesis, 166, 320 Protease, 56, 70, 320 Protein C, 56, 67, 127, 200, 263, 266, 268, 289, 299, 301, 320, 335 Protein Conformation, 263, 299, 320 Protein S, 60, 70, 176, 199, 233, 234, 269, 274, 285, 320, 325 Proteinuria, 309, 320 Proteoglycans, 268, 286, 320 Proteolytic, 276, 320 Protocol, 5, 11, 51, 74, 320 Protons, 263, 294, 320, 322 Protozoa, 277, 305, 320 Proximal, 282, 308, 320 Pruritic, 282, 320 Pruritus, 191, 320 Pseudomonas, 85, 108, 149, 153, 307, 320 Psoriasis, 190, 191, 308, 320 Psychiatric, 276, 305, 321 Psychiatry, 80, 287, 321, 336 Psychoacoustic, 20, 25, 41, 63, 205, 321 Psychomotor, 304, 321 Psychophysics, 321 Public Health, 14, 17, 21, 26, 28, 50, 66, 69, 87, 118, 183, 231, 241, 321 Public Policy, 229, 321 Publishing, 6, 31, 88, 196, 204, 205, 206, 321 Pulmonary Ventilation, 321, 324

Index 351

Pulse, 70, 166, 306, 321 Pupil, 281, 308, 321 Purifying, 85, 321 Purines, 321, 327 Purulent, 20, 112, 169, 171, 172, 261, 312, 321 Pyelonephritis, 82, 321 Q Quality of Life, 4, 129, 321 Quinolones, 28, 321 R Race, 25, 184, 306, 321 Radiation, 193, 262, 284, 286, 288, 295, 298, 322, 337 Radiation therapy, 193, 262, 286, 298, 322, 337 Radioactive, 292, 294, 295, 298, 306, 307, 310, 322, 337 Radiography, 289, 322 Radiolabeled, 298, 318, 322, 337 Radiotherapy, 270, 299, 322, 337 Random Allocation, 322 Randomization, 40, 86, 322 Randomized, 15, 21, 23, 31, 32, 34, 35, 40, 66, 75, 77, 87, 94, 95, 106, 115, 127, 129, 150, 161, 283, 322 Randomized Controlled Trials, 21, 77, 129, 322 Reagent, 73, 302, 322 Receptor, 36, 57, 65, 68, 82, 83, 142, 181, 187, 191, 261, 265, 303, 322, 327 Recombinant, 55, 180, 186, 322, 336 Recombinant Proteins, 55, 322 Recombination, 114, 277, 322 Reconstitution, 65, 82, 323 Rectum, 266, 270, 281, 288, 289, 296, 300, 320, 323 Recur, 35, 323 Recurrence, 11, 13, 23, 33, 34, 35, 112, 136, 141, 323 Red blood cells, 285, 293, 323, 326 Red Nucleus, 267, 323 Reductase, 33, 323 Refer, 1, 9, 10, 276, 282, 287, 288, 301, 307, 310, 323, 336 Reflex, 5, 74, 323 Reflux, 96, 118, 289, 323 Refraction, 308, 323, 329 Refractory, 4, 34, 37, 323 Regeneration, 323 Regimen, 10, 283, 323 Regression Analysis, 75, 323

Regurgitation, 289, 323 Relapse, 11, 323 Remission, 323 Repressor, 55, 311, 323 Resolving, 97, 324 Resorption, 40, 68, 270, 312, 324 Respiration, 271, 306, 313, 324 Respirator, 304, 324, 336 Respiratory Mucosa, 56, 57, 70, 324 Respiratory Physiology, 324, 336 Respiratory syncytial virus, 28, 30, 44, 103, 117, 324 Respiratory Syncytial Virus Infections, 28, 324 Respiratory System, 188, 262, 307, 324 Response Elements, 85, 324 Response rate, 23, 324 Restoration, 34, 196, 205, 244, 323, 324, 337 Retina, 277, 300, 308, 324, 325, 337 Retinal, 187, 311, 324 Retinal Detachment, 187, 324 Retinoblastoma, 233, 325 Retinol, 324, 325 Retrospective, 3, 6, 325 Retrospective study, 6, 325 Reverse Transcriptase Polymerase Chain Reaction, 103, 325 Rheumatism, 325 Rheumatoid, 191, 325 Rheumatoid arthritis, 191, 325 Rhinitis, 9, 58, 61, 77, 141, 175, 177, 179, 191, 199, 263, 271, 284, 325, 327 Rhinorrhea, 182, 325 Rhinovirus, 60, 61, 103, 325 Ribose, 261, 279, 325 Ribosome, 325, 334 Rigidity, 316, 325 Rod, 268, 292, 320, 325 Round Window, 88, 89, 325 Rubber, 179, 261, 325 Rubella, 17, 325 S Saccule, 325, 336 Saline, 186, 211, 325 Saliva, 172, 326 Salivary, 127, 172, 281, 287, 313, 326, 330 Salivary glands, 172, 281, 287, 326 Salivation, 182, 326 Saponins, 326, 329 Scleroproteins, 299, 326 Sclerosis, 233, 326, 335

352 Otitis Media

Screening, 25, 50, 59, 63, 74, 92, 93, 130, 153, 168, 169, 171, 199, 207, 245, 275, 304, 326 Sebaceous, 299, 326 Sebaceous gland, 299, 326 Secretion, 68, 71, 80, 182, 183, 184, 191, 244, 279, 285, 290, 293, 306, 307, 313, 326 Segmental, 77, 326 Segmentation, 326 Segregation, 322, 326 Seizures, 314, 326 Semen, 320, 326 Semicircular canal, 297, 326 Semisynthetic, 264, 272, 273, 274, 275, 326 Sepsis, 67, 186, 326 Septic, 266, 326 Septicaemia, 326, 327 Septicemia, 50, 56, 64, 326 Sequela, 38, 67, 171, 327 Sequencing, 38, 50, 196, 317, 327 Serine, 56, 327 Serologic, 295, 327 Serotypes, 64, 123, 141, 182, 327 Serous, 85, 103, 113, 150, 158, 171, 184, 200, 207, 211, 212, 243, 284, 306, 327 Serum, 19, 55, 60, 61, 84, 103, 140, 200, 264, 265, 276, 295, 302, 306, 323, 327, 335 Sessile, 69, 327 Sex Determination, 233, 327 Side effect, 6, 32, 87, 221, 262, 269, 327, 333 Signal Transduction, 37, 57, 68, 76, 327 Signs and Symptoms, 30, 31, 171, 242, 323, 327 Skeleton, 299, 319, 327 Skull, 16, 270, 274, 327, 332 Smooth muscle, 264, 293, 308, 327, 328, 330 Sneezing, 315, 327 Snoring, 22, 328 Social Behavior, 73, 328 Social Environment, 321, 328 Sodium, 172, 193, 223, 306, 328, 331 Sodium Fluoride, 172, 328 Soft tissue, 49, 270, 327, 328 Solitary Nucleus, 267, 328 Solvent, 290, 312, 328 Sorbitol, 87, 172, 176, 303, 328 Sound wave, 277, 328 Spasm, 269, 328 Spasmodic, 182, 315, 328 Spastic, 182, 328 Spasticity, 328

Spatial disorientation, 282, 328 Specialist, 23, 167, 247, 279, 281, 328 Specificity, 59, 84, 262, 266, 329 Spectrum, 40, 264, 270, 272, 273, 311, 329 Speech Disorders, 47, 329 Speech Perception, 4, 74, 204, 205, 329 Sperm, 264, 274, 329 Sphenoid, 313, 329 Spinal cord, 270, 273, 274, 282, 283, 305, 309, 313, 315, 323, 329, 331 Spiral Lamina, 329, 335 Splenomegaly, 296, 329 Sporadic, 325, 329 Sputum, 181, 182, 187, 193, 329 Squamous, 274, 329 Squamous Epithelium, 274, 329 Standard therapy, 46, 329 Stapedius, 101, 329 Stapes, 31, 169, 171, 296, 312, 329 Statistically significant, 6, 329 Sterile, 13, 26, 69, 266, 329 Sterilization, 174, 329 Steroid, 35, 96, 131, 143, 196, 204, 214, 244, 326, 329, 330 Steroid therapy, 196, 204, 244, 330 Stimulant, 293, 330 Stimulus, 47, 286, 297, 298, 300, 314, 321, 323, 330, 332 Stomach, 182, 261, 268, 269, 281, 285, 289, 294, 302, 308, 315, 323, 330 Strabismus, 182, 330 Strand, 317, 330 Streptococcal, 50, 112, 301, 330 Streptococci, 89, 97, 107, 119, 307, 330 Stress, 10, 19, 25, 26, 28, 205, 267, 308, 318, 325, 330, 336 Stroke, 164, 228, 330 Styrene, 325, 330 Subacute, 178, 296, 327, 330 Subclinical, 131, 296, 326, 330 Subcutaneous, 272, 282, 288, 330 Sublingual, 182, 330 Submaxillary, 285, 330 Submucous, 17, 330 Subspecies, 328, 330 Substance P, 285, 323, 326, 330 Substrate, 33, 58, 294, 309, 331 Sulfisoxazole, 14, 331 Sulfur, 286, 331 Suppression, 62, 279, 331 Surdity, 178, 331 Surfactant, 189, 331

Index 353

Sweat, 193, 273, 331 Sweat Glands, 273, 331 Sympathetic Nervous System, 267, 331 Sympathomimetic, 182, 310, 315, 331 Symphysis, 320, 331 Symptomatic, 13, 18, 169, 171, 331 Synaptic, 327, 331 Synergistic, 65, 331, 333 Systemic disease, 56, 326, 331 T T cell, 62, 80, 192, 297, 331 Tachycardia, 268, 331 Tachypnea, 268, 331 Tear Gases, 299, 332 Teichoic Acids, 291, 332 Telangiectasia, 233, 332 Telecommunications, 277, 332 Temporal, 11, 16, 46, 63, 73, 201, 203, 292, 304, 332 Testosterone, 323, 332 Tetani, 332 Tetanic, 332 Tetanus, 17, 332 Thalamic, 267, 332 Thalamic Diseases, 267, 332 Therapeutics, 25, 45, 111, 121, 147, 148, 223, 332 Thermal, 281, 310, 317, 332 Threonine, 327, 332 Threshold, 6, 8, 15, 74, 332 Thrombin, 316, 320, 332 Thrombocytopenia, 316, 332 Thrombomodulin, 320, 332 Thrombophlebitis, 182, 332 Thrombosis, 99, 120, 174, 268, 278, 305, 320, 330, 332 Thromboxanes, 266, 283, 332 Thrombus, 278, 296, 316, 332, 333 Thymus, 295, 302, 333 Thyroid, 298, 333, 335 Tic, 27, 44, 214, 285, 302, 307, 333 Tin, 317, 333 Tinnitus, 257, 312, 333 Tolerance, 70, 282, 333 Tomography, 132, 276, 277, 333 Tonal, 8, 333 Tonic, 269, 333 Tonsil, 135, 333 Tonsillitis, 17, 333 Tooth Preparation, 261, 333 Topical, 25, 108, 125, 132, 133, 143, 144, 173, 177, 182, 214, 266, 313, 318, 333

Torticollis, 182, 333 Toxic, iv, 168, 277, 281, 284, 295, 330, 333, 334 Toxicity, 282, 305, 310, 333 Toxicology, 230, 334 Toxins, 265, 283, 296, 306, 326, 334 Toxoid, 66, 334 Toxoplasmosis, 267, 334 Trace element, 310, 333, 334 Transcriptase, 13, 64, 103, 325, 334 Transcription Factors, 84, 85, 324, 334 Transcutaneous, 51, 334 Transduction, 37, 57, 68, 75, 327, 334 Transfection, 269, 334 Transfer Factor, 295, 334 Transferases, 291, 334 Translation, 77, 285, 334 Translational, 40, 334 Translocation, 274, 285, 334 Transmitter, 261, 304, 310, 334 Transplantation, 274, 295, 303, 334 Trauma, 268, 292, 309, 332, 333, 334 Treatment Failure, 6, 8, 12, 21, 26, 34, 162, 334 Treatment Outcome, 21, 33, 335 Trees, 325, 335 Tremor, 233, 285, 335 Trimethoprim-sulfamethoxazole, 26, 98, 335 Tuberculosis, 277, 335 Tuberous Sclerosis, 233, 335 Tumor Necrosis Factor, 64, 66, 68, 91, 108, 117, 335 Tympani, 114, 335 Tympanum, 200, 335 Tyrosine, 299, 335 U Ulcer, 272, 335 Ulcerative colitis, 177, 296, 335 Ultrasonography, 289, 335 Unconscious, 280, 294, 335 Uracil, 335, 336 Urea, 331, 335 Urethra, 320, 335, 336 Uridine Triphosphate, 173, 336 Urinary, 272, 274, 284, 296, 311, 335, 336 Urinary tract, 272, 336 Urine, 269, 276, 282, 285, 293, 296, 311, 320, 335, 336 Urticaria, 190, 264, 336 Uvula, 328, 336

354 Otitis Media

V Vaccination, 17, 44, 51, 61, 64, 86, 129, 134, 210, 336 Vascular, 28, 264, 284, 296, 310, 333, 336 Vasodilator, 270, 293, 336 Vector, 170, 193, 313, 334, 336 Vein, 310, 332, 336 Venous, 268, 320, 336 Ventilator, 304, 324, 336 Ventricle, 278, 294, 321, 336 Venules, 270, 336 Vertigo, 257, 312, 336 Vestibular, 58, 59, 67, 201, 336 Vestibule, 166, 275, 297, 312, 325, 326, 336 Vestibulocochlear Nerve, 267, 275, 333, 336 Veterinary Medicine, 229, 337 Viral Vaccines, 6, 337 Virulence, 45, 49, 50, 51, 53, 54, 57, 67, 70, 81, 82, 83, 84, 88, 90, 91, 115, 116, 267, 269, 333, 337

Visceral, 267, 337 Visceral Afferents, 267, 337 Viscosity, 142, 149, 193, 261, 337 Vitreous Humor, 324, 337 W Watchful waiting, 135, 203, 337 White blood cell, 265, 268, 296, 300, 302, 303, 307, 310, 316, 331, 337 Whooping Cough, 315, 337 Wound Healing, 307, 337 X Xenograft, 264, 337 X-ray, 257, 276, 277, 288, 298, 310, 322, 337 X-ray therapy, 299, 337 Y Yeasts, 288, 315, 338 Yttrium, 166, 338 Z Zygote, 277, 338 Zymogen, 320, 338

Index 355

356 Otitis Media

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