ERYTHROMYCIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
ii
ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Erythromycin: 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: 0-597-84414-3 1. Erythromycin-Popular works. I. Title.
iii
Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.
iv
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on erythromycin. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
v
About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
vi
About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
vii
Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ERYTHROMYCIN........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Erythromycin ................................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 31 The National Library of Medicine: PubMed ................................................................................ 45 CHAPTER 2. NUTRITION AND ERYTHROMYCIN .............................................................................. 69 Overview...................................................................................................................................... 69 Finding Nutrition Studies on Erythromycin............................................................................... 69 Federal Resources on Nutrition ................................................................................................... 74 Additional Web Resources ........................................................................................................... 74 CHAPTER 3. ALTERNATIVE MEDICINE AND ERYTHROMYCIN ....................................................... 77 Overview...................................................................................................................................... 77 National Center for Complementary and Alternative Medicine.................................................. 77 Additional Web Resources ........................................................................................................... 81 General References ....................................................................................................................... 83 CHAPTER 4. DISSERTATIONS ON ERYTHROMYCIN ......................................................................... 85 Overview...................................................................................................................................... 85 Dissertations on Erythromycin.................................................................................................... 85 Keeping Current .......................................................................................................................... 86 CHAPTER 5. CLINICAL TRIALS AND ERYTHROMYCIN .................................................................... 87 Overview...................................................................................................................................... 87 Recent Trials on Erythromycin.................................................................................................... 87 Keeping Current on Clinical Trials ............................................................................................. 88 CHAPTER 6. PATENTS ON ERYTHROMYCIN .................................................................................... 91 Overview...................................................................................................................................... 91 Patents on Erythromycin............................................................................................................. 91 Patent Applications on Erythromycin ....................................................................................... 104 Keeping Current ........................................................................................................................ 122 CHAPTER 7. BOOKS ON ERYTHROMYCIN ...................................................................................... 125 Overview.................................................................................................................................... 125 Book Summaries: Online Booksellers......................................................................................... 125 Chapters on Erythromycin......................................................................................................... 126 CHAPTER 8. PERIODICALS AND NEWS ON ERYTHROMYCIN ........................................................ 133 Overview.................................................................................................................................... 133 News Services and Press Releases.............................................................................................. 133 Newsletter Articles .................................................................................................................... 135 Academic Periodicals covering Erythromycin ........................................................................... 136 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 137 Overview.................................................................................................................................... 137 U.S. Pharmacopeia..................................................................................................................... 137 Commercial Databases ............................................................................................................... 138 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 143 Overview.................................................................................................................................... 143 NIH Guidelines.......................................................................................................................... 143 NIH Databases........................................................................................................................... 145 Other Commercial Databases..................................................................................................... 147 APPENDIX B. PATIENT RESOURCES ............................................................................................... 149 Overview.................................................................................................................................... 149 Patient Guideline Sources.......................................................................................................... 149
viii Contents
Finding Associations.................................................................................................................. 152 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 155 Overview.................................................................................................................................... 155 Preparation................................................................................................................................. 155 Finding a Local Medical Library................................................................................................ 155 Medical Libraries in the U.S. and Canada ................................................................................. 155 ONLINE GLOSSARIES................................................................................................................ 161 Online Dictionary Directories ................................................................................................... 161 ERYTHROMYCIN DICTIONARY ............................................................................................. 163 INDEX .............................................................................................................................................. 229
1
FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with erythromycin 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 erythromycin, 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 erythromycin, 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 erythromycin. 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 erythromycin, 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 erythromycin. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON ERYTHROMYCIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on erythromycin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and erythromycin, 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 “erythromycin” (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: •
Erythromycin and Amoxicillin? Source: Journal of the Tennessee Dental Association. 81(1): 34-36. Winter 2001. Contact: Available from Journal of the Tennessee Dental Association. 2104 Sunset Place, Nashville, TN 37212. E-mail:
[email protected]. Summary: A large number of patients with odontogenic (arising in the teeth) infections are referred to the graduate and undergraduate oral surgery clinics at the University of Tennessee, College of Dentistry. These patients have often been placed on antibiotics by the referring dentist. Two of the more commonly prescribed antibiotics are erythromycin and amoxicillin. This article provides a brief review of the antibiotics most commonly used to treat odontogenic infections, and illustrates why erythromycin and amoxicillin may not be the best choice. Other drugs discussed include penicillin,
4
Erythromycin
cephalosporins, clindamycin, and metronidazole. The author concludes that two drugs that are effective alternatives in the penicillin allergic patient are cephalexin and clindamycin. They are bactericidal and effective against the oral streptococci and oral anaerobes that cause most odontogenic infections. 5 references. •
Octreotide Enhances the Accelerating Effect of Erythromycin on Gastric Emptying in Healthy Subjects Source: Alimentary Pharmacology and Therapeutics. 16(8): 1563-1570. August 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email:
[email protected]. Website: www.blackwell-science.com. Summary: Erythromycin exhibits gastrokinetic properties through cholinergic pathways. Reports regarding the action of octreotide on gastric emptying are conflicting. This article reports on a study undertaken to assess the hypothesis that serotonin receptors are involved in the accelerating effect of erythromycin on gastric (stomach) emptying; and any modification of the gastrokinetic action of erythromycin induced by octreotide. Gastric emptying of a standard meal was estimated in 20 healthy subjects by scintigraphy on three different occasions in 3 conditions: after placebo, after 200 milligrams of intravenous erythromycin, and after 200 milligrams of intravenous erythromycin following pretreatment with either 4 milligrams of intravenous ondansetron or 50 micrograms octreotide. Erythromycin significantly accelerated gastric emptying in all subjects by abolishing the lag phase. Pretreatment with ondansetron abolished the accelerating effect of erythromycin by restoring the emptying times to placebo levels. Octreotide significantly enhanced the accelerating effect of erythromycin by reducing both the lag and post-lag phases of gastric emptying. 7 figures. 1 table. 41 references.
Federally Funded Research on Erythromycin The U.S. Government supports a variety of research studies relating to erythromycin. 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 erythromycin. 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 erythromycin. The following is typical of the type of information found when searching the CRISP database for erythromycin:
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
•
Project Title: 13C ERYTHROMYCIN
13C
CORRELATION
SPECTROSCOPY
OF
U
5
13C
Principal Investigator & Institution: Rienstra, Chad M.; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002 Summary: In addition to the developments described below, we have recently demonstrated highly precise internuclear distance measurements with the CMR7 pulse sequence. Homonuclear couplings can be measured to a precision of better than 5 Hz with this approach, implying internuclear distance measurements of better than 0. 1-0.2 A precision out to 4-5 'A. We have developed a pulse sequence for efficient doublequantum dipolar recoupling in multiple spin systems under magic-angle-spinning NMR, based on the C7 sequence of Levitt and co-workers. For two-spin systems, the C7 sequence offers higher overall polarization transfer and double-quantum filtration (DQF) efficiency (-73%) than the MELODRAMA sequence (-52%), because the dependence of the recoupled interaction on rotor phase is eliminated. Experimentally, however, DQF efficiency with the C7 sequence depends significantly on the errors that arise from cross terms between chemical shifts and radiofrequency (rf) field inhomogeneity. Many applications require the excitation of DQ coherence in multi-spin systems, which display a wide range of isotropic and anisotropic chemical shifts. Also, the experimental reliability of the sequence is crucial for successful implementation under conditions of low sensitivity and temperature. To meet these requirements, we have constructed a pulse sequenc e that recouples dipolar interactions independent of chemical shifts, by combining Cn elements of various symmetries. The error terms inherent to the C7 sequence are removed by composite MLEV-type rotations; therefore, we refer to the new sequence as CMR7 (Combined MLEV-Refocusing with C7). We have demonstrated the utility of this approach with double-quantum filtration of U-"Clabeled amino acids and "C-"C chemical shift correlation spectroscopy of the U-"C-labeled antibiotic, erythromycin A. With 73% polarization transfer, the ratio of crosspeak to diagonal intensity is expected to be almost 3: 1, and in two-spin cases such as U- "C, "NGly, we have observed better than 2: 1 relative intensities in 2D spectra. However, the full theoretical DQF efficiency is usually not realized in multi-spin systems and similar behavior is observed in correlation spectra with respect to crosspeak intensities. Nevertheless, in many cases crosspeak intensities exceed the diagonal peaks, and in favorable instances the ratio of intensities is greater than 2: 1, even in the multi-spin limit. An illustrative example of these effects, and the improvement in resolution observed upon extending to a second 13C chemical shift dimension, is provided by the U-"C-labeled macrolide antibiotic erythromycin A (EA). EA inhibits protein synthesis by binding to a bacterial ribosome. Actual structural information on the erythromycinribosome complex has been inaccessible due to the paucity of available crystal s and poor resolution of the solution NMR spectra due to the slow reorientational motion of the ribosome. As a result, the erythromycin-ribosome complex exhibits a solid-state NMR spectrum even in solution. Therefore, in order to facilitate structural studies of EA in both its free and complexed forms, it is necessary to make unambiguous chemical shifts assignments in the solid state. We have accomplished the chemical shift assignments using the CMR7 method and are pursuing further structural studies based upon the CMR7 method. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
6
•
Erythromycin
Project Title: 13C ERYTHROMYCIN BREATH TEST TO DETERMINE DRUG DOSAGES Principal Investigator & Institution: Watkins, Paul B.; Professor of Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: A NEW LEWIS ACID CATALYZED CLAISEN REARRANGEMENT Principal Investigator & Institution: Macmillan, David W.; None; California Institute of Technology Mail Code 201-15 Pasadena, Ca 91125 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Principal Investigator's Abstract) The objective of this research proposal is to invent catalytic synthetic methods that allow enantioselective access to structural and stereochemical motifs, which although common among anti-viral, anti-cancer, antibacterial and anti-inflammatory medicinal agents, connot be readily accessed using conventional methods. In this endeavor, we target processes that are readily applied within the related discipline of enantioselective catalysis and therefore will have a direct and immediate impact on the production of single enantiomer drugs with established biological importance. Our intent is to develop synthetic methods of broad utility and function that will ultimately provide new chemical tools for the diverse range of biomedical researchers that utilize molecule construction. As a consequence, this core research will prove valuable to a number of wide-ranging therapeutical areas. One of the most powerful tools for carbon-carbon bond formation in organic synthesis is the Claisen (3,3)-sigmatropic rearrangement. Remarkably, however, an enantioselective catalytic variant of this reaction has yet to be developed. This proposal outlines a new Lewis acid catalyzed Claisen rearrangement that is amenable to enantioselective catalysis and therefore the construction and modification of a diverse range of biologically important molecules and targets. The strategy is predicated on a new Lewis acid catalyzed Claisen rearrangement recently developed in our laboratory. We have already successfully demonstrated that this catalytic methodology is applicable to the construction of an unusually diverse spectrum of structural motifs. A major goal of this research is to utilize this powerful carbon-carbon bond forming methodology to expedite the synthesis of complex targets with important biological activity. One such example is the proposed general strategy towards the total syntheses of the briaranes, a marine metabolite family with extensive medicinal potential that have yet to be accessed through synthetic construction. This proposal outlines a new Lewis acid catalyzed tandem acyl-Claisen rearrangement that is broadly useful for the rapid construction of molecular complexity from simple reagents. This work will develop an innovative strategy for the one-step synthesis of stereochemically complex acyclic frameworks based upon a new tandem-Claisen reaction sequence. Having demonstrated the feasibility of this transformation, we hope to determine the scope and limitations of this catalytic tandem reaction methodology for the production of a range of functional, stereochemical and structural motifs. This methodology will be used in conjunction with our acyl-Claisen reaction for the highly expeditious synthesis of erythronolide B; a member of the erythromycin antibiotic class. This new chemical tool should prove valuable for the rapid construction of erythronolide analogues; an important area of research for treatment of resistant bacterial strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
7
Project Title: ANTIBIOTIC HYPERSUSCEPTIBILITY MUTATIONS IN BACTERIA Principal Investigator & Institution: Neyfakh, Alex A.; Associate Professor; Medicinal Chem & Pharmacognosy; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): The escalating problem of bacterial resistance to antibiotics calls for radical changes in the existing antibacterial therapies. One of the most promising approaches is the use of antibiotic potentiators, compounds that make bacterial cells hypersusceptible to antibiotics. The goal of the project is to identify multiple novel molecular targets for potentiators. This will be accomplished by isolating antibiotic hypersusceptibility mutations of Gram-negative bacteria, Acinetobacter and/or Escherichia coli. These mutations will specify bacterial proteins whose inhibition is likely to potentiate antimicrobial action of antibiotics. Antibiotic hypersusceptibility is a very difficult phenotype to select, and only few such mutations are known. We have designed and tested a novel genetic strategy for selection of hypersusceptibility mutations, termed SDR. Application of this strategy will identify multiple mutations increasing bacterial susceptibility to beta-lactams (ampicillin, ceftazidime, imipenem), translational inhibitors (erythromycin, linezolid, tetracycline, and chloramphenicol) and fluoroquinolone antibiotics (ciprofloxacin). The molecular mechanisms underlying the effects of the most interesting of these mutations will be analyzed. In addition to identifying promising targets for potentiators, the project will help unravel new aspects of the mechanism of action of antibiotics and new features of bacterial physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: FORMATION
ANTIBIOTIC
INHIBITION
OF
BACTERIAL
RIBOSOME
Principal Investigator & Institution: Champney, William S.; Biochem and Molecular Biology; East Tennessee State University Box 70565 Johnson City, Tn 37601 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 28-FEB-2005 Summary: (provided by applicant): The current resurgence of antibiotic-resistant organisms underscores the importance of gaining a better understanding of antibiotic mechanisms, resistance modes and the structural features necessary for optimal effectiveness. The overall objective of this proposal is to learn how five structurally different antibiotics inhibit the process of bacterial cell growth. This investigation will explore the new observation that macrolide antibiotics as well as the ketolides, lincosamides, streptogramin B compounds and oxazolidinones can all inhibit the assembly of the large ribosomal subunit in bacterial cells. Ribosome formation will be analyzed in Staphylococcus aureus and Escherichia coli cells to define the inhibitory features of these compounds. The mechanism of subunit assembly inhibition will be tested by examining the components of the subunit precursor particles which accumulate in the presence of the antibiotic. Aspects of the breakdown of the inhibited assembly intermediate will also be studied. Ribosomal subunits will be reconstituted from component RNAs and proteins to define the molecules involved as targets for assembly inhibition. An investigation of this assembly-sensitive site and the mode of inhibition of assembly will reveal how certain antibiotics can have two inhibitory activities. The findings from this work will help in assessing the effectiveness of existing antibiotics and in developing new compounds as antimicrobial agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
8
•
Erythromycin
Project Title: ANTIBIOTIC ENGINEERING
REGULATORY
GENES
AND
METABOLIC
Principal Investigator & Institution: Reeves, Andrew R.; Fermalogic, Inc. Chicago Technology Park Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-AUG-2003 Summary: (provided by applicant): Strain improvement of commercial fermentations helps to reduce the cost of production of existing pharmaceuticals and helps industry to meet the growing demands for desperately needed new products, such as antibiotics, that can be produced in large enough quantities and at prices the public can afford. This project focuses on strain improvement in a bacterium that generates a widely used antibiotic, erythromycin. This bacterium, Saccharopolyspora erythraea, is a member of the Actinomycete family and is widely used in academic research and industry, making it an excellent model system for this work. The objective of this project is to identify and manipulate genes responsible for controlling erythromycin yield during fermentation. In Phase I a mutagenic plasmid insertion library was created in Sac. erythraea and four classes of morphological and pigmentation mutants were found using a simple visual screen. Three classes of mutants were found that showed significant increases in erythromycin production. An efficient plasmid rescue technique allowed recovery of the integrated plasmid and DNA sequence analysis of the plasmid insert. In Phase II the screening and mutant analysis will continue. The strain improvement genes found could have general application to strain improvement programs for other drugs. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTI-INFECTIVES WITH MULTI-DOMAIN RIBOSOMAL BINDING Principal Investigator & Institution: Katz, Leonard; Vice Present of Biological Sciences; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2003 Summary: Resistance to macrolide antibiotics has increased at alarming rates in recent years, driving the need to develop new and more effective antibiotics. The long term objective of this proposal is to develop a novel 16-membered macrolide antibiotic that is active against erythromycin-resistant Streptococcus pneumoniae and other Gram positive pathogens and which can be produced at reasonable cost. The proposed compound is designed to exhibit its potency through the novel mechanism of synergistic multi-domain ribosomal binding. Consequently, the compound should not induce macrolide resistance and evade all known efflux mechanisms that confer macrolide resistance. Phase I is a proof of principle project to produce a small series of derivatives of a 16- membered macrolide that is a readily available fermentation product, and determine whether the derivatives bind to domain II of the ribosomes and exhibit increased potency against macrolide-resistant strains. Phase II Specific Aims will be to optimize the derivatives to achieve oral bioavailability. Lead compounds will be examined in vitro and in animals for efficacy, toxicity and pharmacokinetics with the intent of advancing one or more to clinical development. PROPOSED COMMERCIAL APPLICATION: Clinical development candidates could be commericialized as antiinfective agents only after approval by the appropriate regulatory authorities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
9
Project Title: BIOSYNTHESIS OF MICROBIAL POLYKETIDES Principal Investigator & Institution: Cane, David E.; Vernon K. Krieble Professor of Chemistry; Chemistry; Brown University Providence, Ri 02912 Timing: Fiscal Year 2002; Project Start 01-AUG-1977; Project End 31-JUL-2005 Summary: Ongoing studies of the ensymology of complex polyketide natural product biosynthesis will be continued and extended, with focus on the macrolide antibiotics erythromycin (1), methymycin (2), and tylosin (3), as well as the antitumor metabolite epothilone (4). Each of these metabolites is assembled by exceptionably large, multifunctional, modular proteins known as polyketide synthases (PKSs) that are closely related to fatty acid synthases, both biochemically and genetically. In addition, epothilone synthase contains additional catalytic activities belonging to the class of nonribosomal peptide synthetases (NRPSs). A combination of chemical, enzymological, and molecular genetic techniques this being used to elucidate the molecular basis for the programming of the complex series of reactions responsible for polyketide chain elongation. The emphasis in this work is on the elucidation of the mechanisms of multistep, enzyme-catalyzed transformations leading to formation of biologically important metabolites. It is expected that the results of these studies will be broadly applicable not only to the understanding of polyketide and other natural product biosynthetic processes in general, but will provide fundamental insights into how catalysis and molecular recognition control both product specificity and molecular diversity in Nature. 1) Deoxyerythronolide B synthase (DEBS) is a modular PKS that catalyzes the formation of 6-deoxyerythronolide B (5), the parent aglycone of erythromycin A. Individual modules of the DEBS protein, responsible for catalysis of a single round of polyketide chain elongation and functional group modification, can be expressed in E. coli. These modules will be used to study the biochemical basis for the specificity and selectivity of individual catalytic domains, particularly the ketosynthase (KS) domains that mediate the key polyketide chain-building decarboxylative condensation reaction. 2) The methymycin and tylosin PKSs have intriguing similarities and differences to the well-studied DEBS system. Individual modules of the methymycin/picromycin and tylactone PKSs will be expressed in E. coli in order to investigate their biochemical function and substrate specificity. 3) The EpoA protein, the loading module for the epothilone hybrid PKS/NRPS, will be expressed in E. coli in order to study the EpoAcatalyzed conversion of malonyl-CoA to acetyl-S-EpoA, the substrate for the NRPS module EpoB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: COMPARE GASTRIC ENTERAL FEEDINGS W ERYTHROMYCIN VS TRANSPYLORIC IN CRITICALLY ILL Principal Investigator & Institution: Boivin, Michel; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: EFFECT OF CIRRHOSIS AND SHUNTS ON DRUG DISPOSITION Principal Investigator & Institution: Gorski, J. Christopher.; Associate Professor of Medicine; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167
10
Erythromycin
Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): It is well established that hepatic cirrhosis results in reduced clearance of drugs that are highly metabolized and an enhanced sensitivity to the pharmacological and adverse actions of drugs. Chronic alcohol consumption and hepatitis C are the two most common causes of cirrhosis in the United States with an incidence of 3.1 per 1000 people. The development of portal hypertension is the primary mechanism behind several major complications of cirrhosis such as bleeding from gastroesophageal varices, hepatic encephalopathy, and ascites. Transjugular intrahepatic portosystemic shunts (TIPS) and other surgical shunts are performed to manage these complications of portal hypertension. We have demonstrated that in addition to a reduction in hepatic clearance, cirrhotic patients with TIPS experience an increase in intestinal availability of midazolam, a selective cytochrome P450 3A (CYP3A) substrate. This increased bioavailability primarily reflects a functional lack of intestinal wall firstpass metabolism relative to cirrhotics without TIPS and healthy volunteers. The mechanism for this lack of intestinal wall metabolism is unknown. We propose to characterize the mechanism and consequences of this loss of intestinal wall CYP3A activity in cirrhotics with TIPS by directly examining the CYP3A protein and mRNA levels, intestinal permeability, and in vivo hepatic and intestinal CYP3A activity before, immediately after, and I month after TIPS placement. Cirrhotic patients with TIPS, and potentially other types of portosystemic shunts, are expected to be at risk for excessive pharmacological effects or suffer from an increased incidence of adverse reactions following CYP3A substrate administration. We will examine the susceptibility of these individuals to adverse drug reactions and drug-drug interaction by examining the ability of erythromycin to prolong the QT interval and clarithromycin to inhibit metabolism of buspirone, a CYP3A substrate. Finally, the expression of other enzymes such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs) and pglycoprotein may also be altered in cirrhosis. We will characterize the changes in these enzymes using the partial clearance of acetaminophen to glucuronide (UGT) and sulfate (SULT) conjugates and the disposition of fexofenadine in cirrhotics with and without TIPS and healthy volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENZYMATIC STEREOCHEMISTRY
DETERMINANTS
OF
ERYTHROMYCIN
Principal Investigator & Institution: Summers, Richard G.; Chemistry; University of the South Sewanee, Tn 37375 Timing: Fiscal Year 2000; Project Start 01-SEP-2001; Project End 30-APR-2004 Summary: (adapted from applicant's abstract): The proposed research focuses on the biosynthesis of the clinically important antibiotic erythromycin. It is the long-term goal of this project to produce novel erythromycin derivatives that cannot be prepared by traditional chemical syntheses. New antibiotic derivatives such as these are urgently needed, particularly in light of the increased threat posed by newly emergent antibiotic resistant bacteria. In specific, this work seeks to determine the enzymatic domains that dictate the stereochemistry of the erythromycin macrolactone ring and then use this knowledge to genetically engineer the antibiotic producing bacteria, Saccharopolyspora erythraea, to produce new erythromycin derivatives. Currently, the genes for the erythromycin synthase have been cloned, and much is known about the biosynthesis of this chemically complex antibiotic. Yet, the enzymatic domains responsible for the stereochemical configuration of ten distinct sites in the erythromycin macrolactone ring are unknown. Since it has already been shown that the erythromycin synthase can be
Studies
11
altered to produce new erythromycin derivatives through genetic engineering, knowledge of the determinants of erythromycin stereochemistry should enable the production of entirely new series of antibiotic derivatives, many of which may be biologically active. Indeed, just through alterations in stereochemistry, over a hundred new erythromycins are theoretically accessible. The approach to be taken here centers initially on the in vitro construction of genetic chimeras encoding altered erythromycin synthases using standard recombinant DNA techniques. These altered synthases will feature enzymatic domain interchanges focusing on those domains most likely involved in the determination of erythromycin stereochemistry (i.e. a domain thought to produce one stereochemical outcome will be replaced with an analogous domain thought to produce the opposite stereochemical outcome). Once the genetic chimeras have been constructed in vitro, the wild type genes of the natural erythromycin-producing organism will be replaced (via a two step gene replacement protocol) and the erythromycin derivatives produced by the mutant organisms will be isolated and characterized by NMR. Importantly, most of the work proposed here will be conducted by undergraduate chemistry and biology majors, consequently this research project will also provide an ideal training opportunity for students interested in medical biotechnology and genetic engineering. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF RICKETTSIA PROWAZEKII Principal Investigator & Institution: Wood, David O.; Professor; Microbiology and Immunology; University of South Alabama Mobile, Al 366880002 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): Members of the genus Rickettsia are the etiologic agents of rocky mountain and other spotted fevers and endemic, scrub and epidemic typhus, diseases that pose a pernicious health threat worldwide. Rickettsia prowazekii, the etiologic agent of epidemic typhus is an obligate intracellular parasitic bacterium that can grow only within the cytoplasm of a eucaryotic host cell. The ability of rickettsiae to exploit this intracellular niche in animals as diverse as arthropods and humans and to subsequently cause serious human disease provides the impetus for this study. This proposal focuses on the development and application of genetic techniques to address questions regarding the pathogenic bacterium R. prowazekii and its obligate intracytoplasmic existence. It exploits the availability of the R. prowazekii genome sequence and the development of rickettsial genetic technologies to test hypotheses related to rickettsial gene function, DNA replication, and pathogenic mechanisms. In Specific Aim 1 the PI's goal is to capitalize on a rickettsial transformation system and identification of a selectable antibiotic resistance gene that can be expressed in R. prowazekii to discriminate, via knockouts, essential function at the level of single genes. Specifically targeted genes include those that encode products with homology to known virulence genes of other bacteria, genes hypothesized to be expressed only in the arthropod vector, genes hypothesized to be non-functional and part of the process of rickettsial reductive evolution, and finally, genes with homologs within the R. prowazekii genome. In addition, a transposon-based approach will be used to generate random insertion mutants. In Specific Aim 2,the PI's goal is to isolate the functional origin of replication. One approach will attempt to generate a rickettsial mini-chromosome by linking putative origin fragments with the selectable erythromycin-resistant gene, ereB. An alternate method will identify the origin by binding of rickettsial DnaA. Specific Aim 3 will continue the PI's characterization of transcription termination and identification of rickettsial transcriptional changes that
12
Erythromycin
occur just prior to lysis of the host cell. Using ribonuclease protection studies, the PI will determine whether these changes reflect a general property of the rickettsiae by examining additional non-intrinsic termination sites and the effect of cell number on termination at these sites. Modulation of Rho and its correlation to these changes will be addressed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC AND OTHER DETERMINANTS OF IN VIVO CYP3A ACTIVITY Principal Investigator & Institution: Wilkinson, Grant R.; Professor of Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-1982; Project End 30-JUN-2007 Summary: (provided by applicant): CYP3A is the most abundant of the human cytochrome P450 enzymes in both the intestine and liver. As a result, it is involved in the metabolism of over 50 percent of drugs and is an important determinant of first-pass metabolism following oral drug administration. Despite being metabolized by CYP3A, however, different substrates appear to interact with the enzyme in different ways, so that the metabolic clearance of one does not correlate with that of another. One hypothesis to account for this lack of correlation is that it reflects, in part, the different relative contributions of intestinal and hepatic CYP3A, and, thus, the route of drug administration. Drugs with different metabolic characteristics and routes of administration (midazolam, triazolam and alprazolam) will be used to test this hypothesis. A second possibility that will be investigated is that the CYP3A substrateactive site interaction is substrate-dependent, accordingly, drugs may be characterized into different "groups." Correlation within "groups" will, therefore, be present to a far greater extent than between "groups." In addition to the noted benzodiazepines, this hypothesis will be tested with other CYP3A substrates, such as cyclosporine-A, erythromycin and nifedipine, which are postulated to belong to other "groups." An important characteristic of CYP3A is marked interindividual variability in activity (10to more than 40-fold), which significantly contributes to differences in drug responsiveness between subjects. A genetic determinant(s) is considered to be important in this regard but has never been formally defined and may, in fact, be different according to the tissue localization of CYP3A. Accordingly, the inheritability of CYP3A activity will be determined in monozygotic and dizygotic twins to test the hypothesis that a genetic factor is more important in regulating basal CYP3A-mediated metabolism in the liver than that in the intestine, and also in the enzyme?s inducibility at these two sites. Studies are also proposed which will establish the in vivo functional consequences of the allelic variants CYP3A4*1B and CYP3A5*3, and other known single nucleotide polymorphisms (SNPs). Finally, investigations in European-, African-American, and Japanese populations will be undertaken in order to identify SNPs associated with the interindividual variability in CYP3A activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: GENETIC APPROACHES TO VIRULENCE IN B. BURGDORFERI Principal Investigator & Institution: Cabello, Felipe C.; Professor; Microbiology and Immunology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (adapted from the applicant's abstract): Borrelia burgdorferi is an in vitro culturable bacterium that is the cause of Lyme disease. Its small genome contain
Studies
13
approxnnately 1,000 chromosomal genes and 400 plasmid genes. Despite knowledge of the complete DNA sequence of the B. burgdorferi genome, identification and characterization of unique in vivo expressed B. burgdorferi virulence determinants has been delayed by the lack of expeditious and efficacious genetic systems in Borrelia. We have developed a genetic system in B. burgdorfed that consists of the extrachromosomal cloning vector, pGKI2, enhanced green fluorescent protein as a potential reporter gene, and resistance to erythromycin, kanamycin, and other antibiotics as selective markers. We have also been able to show that the bmp gene cluster is highly conserved among B. burgdorferi sensu lato strains, and that the genes of this cluster undergo environmentally modulated differential expression suggesting a potential role in virulence for these genes. The experimental protocol we propose is based on our preliminary work and framed by two hypotheses: 1) efficient molecular genetic systems can be developed for B. burgdorferi, and 2) the role of the bmp gene cluster in B.burgdorferi biology and virulence can be ascertained using these systems. With the long-term aim of identifying B.burgdorferi virulence determinants and improving our understanding of their in vivo expression and regulation, we propose the following Specific Aims: 1) Continue development and improvement of an extrachromosomal cloning system for B. burgdorferi, 2) isolate and complement B. burgdorferi bmpD, bmpC and bmpA null mutants to determine the possible role of these genes in B. burgdorferi virulence in in vitro and in vivo model systems of infection; and 3) characterize promoters and regulatory DNA sequences of bmpC using transcriptional fusions with enhanced green fluorescent protein (EGFP) and fluorescence-activated cell sorting (FACS). We expect these experiments will permit the extension of the molecular Koch's postulates to the characterization of unique aud specific molecular virulence determinants of B. burgdorferi. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GROWTH HORMONE ON CYCLOSPORINE CLEARANCE IN TRANSPLANTED Principal Investigator & Institution: Younas, Asif; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: METABOLIC ENGINEERING OF POLYKETIDE PRODUCTION IN E.COLI Principal Investigator & Institution: Khosla, Chaitan S.; Professor; Chemical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 16-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Polyketide synthases (PKSs) are a family of multienzyme assemblies that catalyze the synthesis of numerous structurally complex and biologically important natural products. Modular PKSs, such as the 6deoxyerythronolide B synthase (DEBS), are a particularly interesting sub-class of PKSs that synthesize complex polyketides such as macrolides. Over the past decade, there has been considerable interest in studying these megasynthases, and in exploiting their modularity and broad substrate specificity for the engineered biosynthesis of "unnatural" natural products. Most products of modular PKSs are produced by relatively uncharacterized bacteria. As a result, every time a new natural product with
14
Erythromycin
promising biological properties is discovered, a considerable amount of time and expense must be incurred to obtain reliable quantities of the compound from natural sources, and an even greater investment is demanded before the biosynthetic pathway becomes amenable to rational engineering. An alternative is to develop robust and generally applicable technologies for the heterologous expression of polyketides in wellcharacterized microbial hosts. During the past proposal period, the metabolism of the model bacterium Escherichia coli was engineered to produce 6-deoxyerythronolide B (6dEB), the macrocyclic core of the antibiotic erythromycin. This engineered strain of E. coli harbors modifications in five endogenous genes; it also contains seven new genes from three different heterologous sources. The resulting cellular catalyst converts exogenous propionate into 6dEB in quantities approaching 200 mg/L over a 5-day process. During the next 3-year proposal period, we will focus on improving and extending the properties of E. coli as a host of choice for the biosynthesis of natural and unnatural polyketides. This will be accomplished through a combination of molecular biological tools, metabolic engineering strategies and fermentation technology development. The Specific Aims are: I] Engineering new pathways for precursor and product biosynthesis in E. coli; II] Improved fermentation protocols for enhancing polyketide productivity in E. coli; III] Further improvements in polyketide productivity of E. coli using functional genornic and metabolic engineering approaches; & IV] Heterologous production of two new complex natural products in E. coli. The implications of this research are 3-fold. First, given the availability of scalable protocols for fermenting E. coli to overproduce bioproducts, the ability to synthesize complex polyketides in this heterologous host will bode well for the practical production of these expensive bioactive natural products as well as their engineered derivatives. Second, the use of E. coli as a host for polyketide production opens the door for harnessing E. coli to engineer modular PKSs using directed and random approaches. Finally, the project is a good opportunity to train students at the interface of metabolic engineering & natural product biosynthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METABOLIC ENGINEERING OF YEAST FOR POLYKETIDE PRODUCTION Principal Investigator & Institution: Kealey, James T.; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 30-APR-2004 Summary: (provided by applicant): The polyketides are a diverse group of natural products with great clinical importance. A major barrier to the high level production of both natural and genetically engineered polyketides has been the lack of a generic heterologous system that (a) functionally expresses the polyketide synthase and accessory enzymes and (b) contains adequate levels of acyl-Coenzyme A substrates. The long term goal of this project is to construct strains of Saccharomyces cerevisiae optimized for polyketide overproduction. In Phase I, we showed that a fungal polyketide could be produced at extremely high levels in S. cerevisiae. We also demonstrated that the three genes for the polyketide precursor of erythromycin could be functionally expressed from separate plasmids in a heterologous Streptomyces host. In Phase II of the project we will: (a) Develop yeast host strains that (i) produce substrates and post-translational enzymes necessary to produce modular polyketides; (ii) have necessary nutritional deficiencies to allow positive selection of at least three compatible plasmids; and (iii) will permit radioactive labeling of -CoA pools and polyketide synthases. (b) Demonstrate that such a strain can express a modular
Studies
15
polyketide synthase and produce a complex polyketide at levels suitable for commercial development. PROPOSED COMMERCIAL APPLICATION: A generic overproducing yeast strain will enable production of commercially valuable polyketides with significant cost and time savings over existing native host organisms and production methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METABOLIC INTESTINAL DRUG INTERACTIONS Principal Investigator & Institution: Thummel, Kenneth E.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term goal of the research described in this grant proposal is to understand the mechanistic basis for inhibitory drug interactions involving human CYP3A4. This is important for the avoidance of adverse events with the numerous drugs in clinical use today that are either a substrate or inhibitor of the enzyme. It will also aid greatly in predicting the in vivo inhibitory potential for new molecular entities under develop. We hypothesize that effects of several clinically important inhibitory drugs on the first-pass clearance of CYP3A substrate occurs predominantly with the intestinal mucosa, and they can last well beyond the period of inhibitor absorption. This will be investigated with the following Specific Aims: I. To determine whether the inhibitory effect of azole anti-fungals on the first-pass metabolism of the CYP3A marker midazolam occurs predominantly within the intestinal mucosa rather than liver, and whether this preferential inhibition persists will beyond the period of inhibitor absorption due to sequestration of inhibitor in the mucosa. II. To determine whether inhibition of intestinal rather than hepatic first-pass is the predominant mechanism by which dialkylamine inhibitors elevate the systemic availability of orally administered midazolam, and to determine whether the time-course of inhibition parallels the formation of a slowly reversible MI-CYP3A complex. III. To determine if the in vivo effect during multiple dosing of a prototype macrolide inhibitor, erythromycin, an oral midazolam bioavailability, depends on the amount of CYP3A4 expressed in the intestinal mucosa and the accumulation over time of the di-desmethyl erythromycin metabolite in that tissue. We will employ three experimental paradigms; pharmacokinetic studies in healthy human volunteers; in vitro metabolic studies in human-derived Caco-2 cell culture monolayers; and in vivo intestinal extraction studies in a domestic pig model. This three-tiered approach should allow us to identify the contribution of readily predictable, reversible interactions between inhibitor and substrate, and current unpredictable, slowly reversible phenomena such as intracellular inhibitor sequestration and MI complex formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: METRONIDAZOLE PRETERM BIRTH IN WOMEN
PLUS
ERYTHROMYCIN
TO
PREVENT
Principal Investigator & Institution: Caritis, Steve N.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: Aims of the study are to 1)determine whether or not the administration of antimicrobial therapy in women with elevated cervical oncofetal fibronectin will reduce the risk of spontaneous preterm birth, reduce the risk of early neonatal sepsis, clinical chorioamnionitis, and early postpartum endometritis, and 2)determine the effect of
16
Erythromycin
antimicrobial therapy on fetal fibronectin positivity and its ability to prevent preterm delivery. Patients are screened at the time of a vaginal exam for the presence of cervical oncofetal fibronectin by obtaining two swabs. If the dipstick test for these swabs is positive, the specimen is sent to a central lab for an ELISA assay for the presence of fetal fibronectin. If the assay is positive, the patient is randomized into the double-blind, placebo-controlled trial of metronidazole 250mg vs. placebo/placebo. Patients take the study drug for 10 days and return for an exam similar to the screening exam. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF HUMAN MDR1 FUNCTION IN VIVO Principal Investigator & Institution: Wood, Alastair J J.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-1982; Project End 30-JUN-2007 Summary: (provided by applicant): Membrane transporters are increasingly recognized to be important in drug disposition. For example, the efflux transporter MDR1 (Pglycoprotein) impairs oral absorption, limits distribution into certain tissues pharmacologic sanctuary sites - and enhances excretion via the liver, kidney and intestinal tract. Accordingly, modulation of MDR1 function by either inhibition or induction can, in principle, significantly alter a drug?s disposition and its pharmacological effect. However, supportive evidence for such changes in humans and, more importantly, their application to beneficially alter drug responsiveness is currently limited. In the case of MDR1 inhibition, the limitation has been the lack of an appropriate potent and selective drug for this purpose. This Project proposes to use a drug with these necessary characteristics as a tool to investigate the consequences and therapeutic potential of MDR1 inhibition in humans. Specific Aim 1 proposes to test the hypothesis that inhibition of MDR1 function affects target tissue availability and drug responsiveness, especially at a pharmacologic sanctuary site such as the brain. This will be accomplished by the use of a probe, wherein MDR1 inhibition would be expected to change it from a centrally ineffective drug into one with efficacy. By contrast, Specific Aim 2 focuses on the effect of MDR1 inhibition on systemic drug availability. Studies are proposed with digoxin and fexofenadine - two drugs that are essentially excreted unchanged and whose disposition appears to be MDR1-dependent. Accordingly, they may serve as in vivo probes for the transporter if such a role is validated. Because of the overlap between MDR1 substrates/inhibitors and those of cytochrome P4503A (CYP3A), studies are also proposed to investigate the selectivity of inhibition of the transporter using midazolam and the erythromycin breath test as in vivo probes of CYP3A. Additional studies will also define the relative contribution of MDR1 and CYP3A in the disposition of drugs like cyclosporine-A and erythromycin, which are substrates of both proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MODULATION OF MULTIDRUG RESISTANCE MECHANISMS Principal Investigator & Institution: Sikic, Branimir I.; Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 15-APR-1990; Project End 31-MAY-2003 Summary: The purpose of this proposal is to conduct clinical trials of modulation of resistance to cytotoxic drugs. Studies of new modulators of MDR1/P-glycoprotein (Pgp) multidrug resistance (MDR) will continue. Additional areas of focus include: (1) modulation of other MDR mechanisms (the MDR-associated protein MRP, and the bcl-2
Studies
17
family of inhibitors of apoptosis); and (2) the use of P-gp inhibitors to enhance the oral bioavailability of taxanes and other P-gp substrate drugs. Aim 1: To conduct Phase I trials of modulation of multidrug resistance mechanisms. We will conduct 1-2 Phase I trials per year, defining toxicities, optimal doses and schedules, and drug disposition. Planned studies include: PSC 833 (PSC)/Doxil/paclitaxel; LY335979/mitoxantrone; LY335979/doxorubicin/paclitaxel; and other, new MDR1 modulators. Similar approaches will be applied to a new inhibitor of MRP, with doxorubicin and with etoposide; and antisense oligonucleotide drugs against bcl-2 and bcl-xl. We will choose these new agents based on animal toxicology, other preclinical data, and availability for clinical trials. An eventual goal is combined blockade of two mechanisms (e.g., MDR1 and MRP). Aim 2: To study pharmacokinetic interactions associated with modulation of drug resistance. An important issue with modulators of drug resistance is the effect of these drugs on normal tissue function and in particular on the disposition of cytotoxins. Pharmacokinetic studies will involve compartmental methods to further define drug interactions, and validation of optimal sampling strategies with Bayesian estimations. The effect of different modulators (PSC vs. LY335979) on the erythromycin breath test in patients will be used to dissect the role of cytochrome P450 3A4 in these interactions. Ancillary pharmacokinetic studies of mitoxantrone and etoposide for the ECOG and POG trials of MDR1 modulation in acute myeloid leukemias will also be supported. Aim 3: To enhance the oral bioavailability of MDR1-related drugs by co-administration with inhibitors of P-gp. Intestinal P-gp is a major barrier to the absorption of taxanes and other MDR1 related cytotoxins. We will co-administer modulators and cytotoxins in trials designed to enhance bioavailability, and potentially to increase the safety and convenience of chemotherapy. Patients will receive an initial course of the cytotoxin intravenously, followed by sequential courses of the cytotoxin orally together with increasing doses of the P-gp inhibitor. The first protocol in this aim will involve paclitaxel with PSC. Other cytotoxins of interest for this approach include taxotere, etoposide, and vinorelbine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNTHASES
MODULE-MODULE
LINKING
SCHEME
OF
POLYKETIDE
Principal Investigator & Institution: Moffet, David A.; Chemistry; Brown University Providence, Ri 02912 Timing: Fiscal Year 2003; Project Start 30-JUN-2003 Summary: (provided by applicant): Polyketide Synthases (PKSs) are large modular enzymes responsible for the production of numerous medically significant polyketides such as the antibiotic Erythromycin and the antitumor compound Epothilone. Each module of a PKS has its own self-contained catalytic machinery for elongating and chemically modifying a polyketide chain. Nature synthesizes elaborate polyketides by linking together individual PKS modules (each with its own catalytic function) in an assembly-line format. This proposal aims to take advantage of the modular arrangement of PKSs with the hope of synthesizing and discovering novel medically beneficial compounds. The goal of this proposal is to develop an in vitro system for the facile rearrangement and recombination of individual PKS modules. The ability to connect individual PKS modules, without disrupting their natural functions, presents the opportunity for the production and eventual screening of large combinatorial libraries of PKSs, each having the potential to produce novel polyketide compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
18
•
Erythromycin
Project Title: MULTICENTER MATERNAL-FETAL MEDICINE NETWORK Principal Investigator & Institution: Wapner, Ronald J.; Professor; Pediatrics; Mcp Hahnemann University Broad & Vine Sts Philadelphia, Pa 19102 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-MAR-2006 Summary: (provided by applicant): Jefferson Medical College is submitting a competing renewal to the "Cooperative Multicenter Maternal-Fetal Medicine Units Network. Jefferson has been an active and productive participant in the Maternal-Fetal Medicine Units (MFMU) Network over the last four years. The Jefferson Center (JC) has actively recruited for all MFMU protocols and has routinely been among the top centers in patient recruitment, data accuracy, and data reliability. The JC PI is chairman of both the steroid and the genetics subcommittees. JC faculty and staff has partipated on subcommittees, introduced concepts, participated in Steering Committee meetings, and performed secondary analysis of data. The JC provides the Network with over 8,700 deliveries per year of which over 35% are high-risk. All patients are available to participate in trials. The JC has a faculty of 20 Maternal-Fetal Medicine subspecialists with 6 designated physicians having primary responsibility for Network activity. These physicians have adequate protected time. Jefferson has an academic research environment demonstrated by its Network participation to date, participation in other multicenter trials, and existence of an extensive research infrastructure. There are intrapartum and antepartum facilities for research recruitment, hospital staffs experienced in research participation, and a large research staff (nurse coordinator, 3 masters nurses, 6 RNs, 2 research associates, a full-time data base manager and a data entry clerk). The JC has a large academic neonatal service with 1,874 neonates cared for per year by 23 full-time neonatologists. The neonatal unit is submitting an application for participation in the Neonatal Intensive Care Unit (NICU) Network. The JC offers the Network additional expertise in clinical and molecular genetics, ultrasound, and epidemiology. Administrative strength include a large organized perinatal network (>30,000 births per year) providing additional patients when required. The JC has proposed a concept on the timing of cervical cerclage removal following preterm premature rupture of membranes. The supporting documentation for this prospective randomized trial demonstrates the Center?s research acumen as well as the breath and strength of the data base. The JC is strongly committed and prepared to continue active participation in the MFMU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS Principal Investigator & Institution: Sciscione, Anthony; Pediatrics; Mcp Hahnemann University Broad & Vine Sts Philadelphia, Pa 19102 Timing: Fiscal Year 2003; Project Start 01-MAY-1996; Project End 31-MAR-2006 Summary: (provided by applicant): Jefferson Medical College is submitting a competing renewal to the "Cooperative Multicenter Maternal-Fetal Medicine Units Network. Jefferson has been an active and productive participant in the Maternal-Fetal Medicine Units (MFMU) Network over the last four years. The Jefferson Center (JC) has actively recruited for all MFMU protocols and has routinely been among the top centers in patient recruitment, data accuracy, and data reliability. The JC PI is chairman of both the steroid and the genetics subcommittees. JC faculty and staff has partipated on subcommittees, introduced concepts, participated in Steering Committee meetings, and performed secondary analysis of data. The JC provides the Network with over 8,700
Studies
19
deliveries per year of which over 35% are high-risk. All patients are available to participate in trials. The JC has a faculty of 20 Maternal-Fetal Medicine subspecialists with 6 designated physicians having primary responsibility for Network activity. These physicians have adequate protected time. Jefferson has an academic research environment demonstrated by its Network participation to date, participation in other multicenter trials, and existence of an extensive research infrastructure. There are intrapartum and antepartum facilities for research recruitment, hospital staffs experienced in research participation, and a large research staff (nurse coordinator, 3 masters nurses, 6 RNs, 2 research associates, a full-time data base manager and a data entry clerk). The JC has a large academic neonatal service with 1,874 neonates cared for per year by 23 full-time neonatologists. The neonatal unit is submitting an application for participation in the Neonatal Intensive Care Unit (NICU) Network. The JC offers the Network additional expertise in clinical and molecular genetics, ultrasound, and epidemiology. Administrative strength include a large organized perinatal network (>30,000 births per year) providing additional patients when required. The JC has proposed a concept on the timing of cervical cerclage removal following preterm premature rupture of membranes. The supporting documentation for this prospective randomized trial demonstrates the Center?s research acumen as well as the breath and strength of the data base. The JC is strongly committed and prepared to continue active participation in the MFMU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW HIGHLY EFFICIENT ROUTES TO POLYKETIDES Principal Investigator & Institution: Calter, Michael A.; Chemistry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 15-DEC-1997; Project End 30-NOV-2002 Summary: (Principal Investigator's) The goal of this project is to develop inexpensive methods for making large amounts of useful drugs. The particular class of compounds that are the focus of this project are the polyketides. These molecules are widely used in clinical practice, particularly as antibiotics. For example, erythromycin is a complex polyketide that has found wide use as an antibiotic, because of its ability to kill bacteria without affecting humans. Physicians use other polyketides as antiviral, antifungal, anticancer and immunosuppressive agents. Although methods do exist for the synthesis of polyketides, the methods described in this proposal are much more applicable to industrial use than existing ones. The most important way in which the proposed chemistry differs from current methods is in the use of a catalytic reaction to prepare the starting materials. Only very small amounts of the catalyst are required in the proposed methods, and it is likely that the catalyst will be reused time and time again. Another advantage of the proposed chemistry is that a number of steps can be run in the same reaction solvent and reactor. This property is very important for industrial syntheses, as each additional solvent and reactor increases the amount of waste and complexity of the process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: NEW KETOLIDE ANTIBACTERIAL DRUGS Principal Investigator & Institution: Hutchinson, Charles R.; Edward Leete Professor; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2003; Project Start 15-FEB-2002; Project End 31-MAY-2006
20
Erythromycin
Summary: (provided by applicant): The long-term goal of this Phase II proposal is the production of new ketolide antibiotics with potent antibacterial activity against macrolide-susceptible and macrolide-resistant bacterial pathogens of humans. In Phase I research, we successfully developed a biological process for production of 15-R-6deoxyerythronolide B, the biochemical precursor of 15-R-erythromycins (R=various chemical groups), that involves expression of the 6-deoxyerythronolide B (DEBS) polyketide synthase (PKS) genes in an Escherichia coli strain carrying the requisite PKS substrate supply genes. In Phase II this process will be optimized for large-scale production of the desired 15-R-6-deoxyerythronolide B (15-R-6dEB) by feeding the 5R-3hydroxy-2-methylpentanoic acid N-acetylcysteamine thioester ("diketide-SNAC") to an E. coli strain expressing the engineered DEBS1 module 2/DEBS2/DEBS3 genes. The resulting 15-R-6dEB will be used subsequently to produce a lead ketolide Kosan has discovered in partnership with another company. The specific aims for the Phase II research are: 1) to determine the relationship between the titer of polyketide produced and the level of DEBS PKS, substrate supply enzymes and substrates. These data will help us design and construct a recombinant E. coli strain that produces >100 mg/L of 15-R-6dEB in a diketide-fed, shake flask fermentation. 2) To isolate, by random mutagenesis of an E. coli strain bearing DEBS PKS and substrate supply genes, mutant strains with a >10-fold increase in 15-R-6dEB titer in a diketide-fed, shake flask fermentation. The improved genetic background of these mutants is expected to enhance the performance of the optimum arrangement of the DEBS PKS and substrate supply genes created in Specific Aim 1. 3) To introduce the optimal metabolically engineered DEBS PKS and substrate supply genes from Specific Aim 1 into the E. coli strain from Specific Aim 2 to create an E. coli recombinant strain that produces >250 mg/L of 15-R-6dEB in a diketide-fed, shake flask fermentation. 4) To optimize the physiological and process parameters for maximum production of 15-R-6dEB at >1 g/L by high cell density E. coli cultures in a 2 liter stirred fermentor. This will be done with a strain obtained through achievement of Specific Aim 3. Several of the ketolide series of analogs based on 15-R-erythromycin A have excellent in vitro and in vivo antibacterial activity, comparable to or better than the leading ketolides in current clinical trials or approved by the FDA for specific uses. We intend to move the best compound to preclinical testing in collaboration with our partner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL DYSMOTILITY
EVALUATION
AND
TREATMENT
OF
GASTRIC
Principal Investigator & Institution: Parkman, Henry P.; Associate Professor; Medicine; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: Gastric dysmotility may be due to delayed gastric emptying, antral hypomotility, and/or gastric dysrhythmias. Gastric motor dysfunction is an important component of several clinical disorders including gastroparesis, functional dyspepsia, and intestinal pseudoobstruction. Our overall hypothesis is that gastric motility can be measured conveniently with noninvasive tests which can have widespread availability and provide clinically relevant information. The studies described in this research protocol will address our long-term research objectives of evaluating and treating disorders of gastric motility using simpler, less expensive, and less invasive techniques. Each of these patient-oriented research protocols involves the close interaction between the principal investigator and beginning clinical investigators in order to encourage and develop their clinical research potential. The first specific aim is to demonstrate the
Studies
21
clinical validity of two novel noninvasive techniques to assess gastric motility. We will develop the 13C-octanoate breath test for gastric emptying into a practical, clinically useful test for the measurement of gastric emptying using an easily prepared standardized meal. We will also assess the clinical utility of a newly modified electrogastrographic instrument that records high frequency gastric myoelectric activity (up to 120 cycles per minute), in addition to the usual 3 cpm activity. The second specific aim is to use these two noninvasive tests (breath testing and electrogastrography) to assess gender-related aspects of gastric motility. We will demonstrate the effects of gender and the menstrual cycle on gastric motility and determine if the changes in gastric motility during the menstrual cycle correlate with estrogen. and progesterone levels. We will determine whether gastric motility is altered during pregnancy, and to investigate if nausea and vomiting that occurs in the first trimester of pregnancy are related to gastric dysmotility and/or alterations of estrogen, progesterone, and/or chorionic gonadotropin blood levels. The third specific aim is to explore novel treatment strategies for abnormal gastric emptying. We will determine whether accelerating or delaying gastric emptying affects postprandial glucose tolerance in diabetic patients. We will determine whether botulinum toxin injection into the pyloric sphincter improves gastric emptying and symptoms in gastroparesis. The fourth specific aim is to enable the principal investigator to continue and even expand his mentoring activities for beginning clinical investigators in patient- oriented research to include mentoring of specialized motility fellows, gastroenterology fellows, medical residents, medical students, and college students. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL INTERMEDIATES
MACROLIDE
AND
KETOLIDE
ANTIBIOTIC
Principal Investigator & Institution: Weber, J Mark.; President; Fermalogic, Inc. Chicago Technology Park Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): The objective of the proposed study is to generate novel macrolide and ketolide structures that may be useful as antibiotics themselves, or as chemical intermediates in the generation of new semi-synthetic antibiotics. Macrolides are effective in the treatment of respirtory infections. The new ketolide derivatives are particularly effective against an emerging public health threat, MLSB resistance (virginiamycin-, tylosin-, streptogramins-, and erythromycin-resistant) Streptococcus. pneumoniae. The new structures will be generated by molecular biotailoring, which is an environmentally low-impact fermentation process, as opposed to chemical synthesis. The project will involve eight biotailoring enzymes, and five macrolide- or ketolide-producing bactieral host strains, in novel combinatorial arrays to create structures that have never before been produced or tested for antibiotic activity. The biotailoring enzymes have been chosen based on analogous structure-activity relationships that show them to impart biological activity to the parent molecule. In addition, a new macrolide biosynthetic gene cluster will be cloned and its gene sequenced obtained in part, to identify new biotailoring enzymes for future work in Phase II. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
22
•
Erythromycin
Project Title: NUCLEIC ACID PROBES OF RIBOSOMAL STRUCTURE AND FUNCTION Principal Investigator & Institution: Cooperman, Barry S.; Professor; Chemistry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-MAR-2004 Summary: The ribosome is the unique site of protein biosynthesis in all cells, and as such a detailed understanding of its structure and function is of fundamental importance to the more general understanding of cellular function at the molecular level. Aside from its intrinsic importance to the basic comprehension of life processes, better understanding of ribosomal function could have important therapeutic consequences. Many antibiotics in current clinical use, such as tetracycline, erythromycin and other macrolides, neomycin and other aminoglycosides, and chloramphenicol target ribosomes as their sites of action. Interest in these ribosomal antibiotics has been growing as bacterial resistance to beta-lactams and quinolines has become more widespread. Several drug companies are now devoting considerable resources toward synthesizing analogues and derivatives of ribosomal antibiotics that overcome bacterial resistance. Better understanding of ribosomal structure and function will be especially important for antibiotics, such as macrolides, where resistance is based on changes in ribosome structure. Our studies will be carried out on the E. coli ribosome, which is by far the best characterized by the studies of many groups, including our own. However, given the considerable conservation of ribosome structure throughout evolution the results we obtain should also be useful for understanding ribosomes from other organisms. The overall goal of this proposal is to describe conformational changes that the ribosome undergoes during specific steps of its functional cycle and how mutations and antibiotic binding affect these changes. We propose to do this by forming defined photocrosslinks from rRNA sites within the ribosome that have been targeted on the basis of their importance for ribosome structure and function, taking advantage of the intrinsic ability of the photocrosslinking process to sample all conformations in solution. Such crosslinks will be formed in different functional states, in wild-type and mutant ribosomes, and in the presence and absence of antibiotics. The structural constraints represented by such crosslinks, along with constraints generated by other approaches, will be used to model structures of the ribosome in specific functional states, using crystal structures of 70S ribosomes and 30S and SOS subunits as initial structures. As our major approach we will continue and refine the use of radioactive, photolabile derivatives of oligonucleotides having sequences complementary to rRNA sequences (PHONTs). Such probes bind to their targeted sequences in intact ribosomal subunits, and, on photolysis, incorporate into neighboring ribosomal components that can subsequently be identified. We also will develop a second approach based on site-specific introduction of photolability into intact rRNA (IPHOR - intact photolabile RNA) to obtain similar information for rRNA sites that are either inaccessible to PHONTs or where the use of PHONTs induces major conformational change. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: OVERPRODUCTION OF POLYKETIDE ANTIMICROBIALS Principal Investigator & Institution: Mcdaniel, Robert N.; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2003; Project Start 15-APR-2000; Project End 31-DEC-2004
Studies
23
Summary: (provided by applicant): Polyketides are a diverse class of natural products with an established history of clinical utility (e.g. erythromycin, FK506, Iovastatin). Conventional strain improvement processes are necessary to make therapeutically important polyketides commercially attractive but are time consuming and tedious. The long term goals of this work are to develop generic approaches to polyketide overproduction and then apply these approaches to the generation of novel polyketide antimicrobials. In this proposal, we are targeting the production of novel erythromycin analogs for lead generation and preclinical development of ketolide and motilide therapeutics. Ketolides are a new class of potent antibiotics with activity against erythromycin sensitive organisms. Motilides are motilin receptor agonists being developed for treatment of gastric pariesis, gastric reflux disease and other uses. The specific aims of this proposal are: i.) to use an erythromycin overproducing system developed in Phase I to express several genetically modified erythromycin PKS genes and produce fully mature erythromycin analogs needed for early and late stage testing, and ii.) to adapt the system to one that will efficiently incorporate synthetic diketideSNAC precursors into the polyketide product and produce erythromycin analogs by precursor-directed biosynthesis. As specific aim iii), we plan to initiate development of a second generation generic overproduction host in the widely used actinomycete host Streptomyces coelicolor. These aims will facilitate the advancement of ketolide and motilide compounds that are in late stage preclinical development, potentially generate new leads for development, and expand the diversity of structures that can be achieved through the genetic manipulation of polyketide synthases in microbiological systems. Furthermore, the establishment of well-defined overproduction hosts will facilitate analyzing the molecular and physiological basis of overproduction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: P450 PHENOTYPE AND CHEMOTHERAPY TOXICITY IN THE ELDERLY Principal Investigator & Institution: Dees, Elizabethh C.; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Interpatient variability in toxic and therapeutic response to chemotherapy remains a major problem in cancer treatment. The long-term goal of this work is to better understand the pharmacologic and pharmacogenetic determinants of this interpatient variability so as to individualize chemotherapy to maximize benefit and minimize toxicity. This is particularly important in older cancer patients, a group that has routinely been excluded from treatment or empirically dosereduced. The central hypothesis of this research plan is that an individual's activity, or phenotype, of relevant drug metabolizing enzymes, which can be determined at the bedside using carefully selected metabolic "probes," can predict that patient's pharmacokinetics (PK) for certain chemotherapy. Further, the results of these probebased tests can be incorporated into models to better tailor dosing. The enzymes targeted in this proposal are the cytochromes P450 (CYPs), particularly the enzyme families CYP2 and CYP3, which represent the major pathways for oxidative metabolism of drugs in the liver. There is large interpatient variation in CYP activity. There are known genetic polymorphisms in many CYPs, but CYP genotype and phenotype may not correlate well in patients with cancer. In addition, age-related decline in CYP expression may be a key factor in increased toxicity in this age group. Probe-based tests that assay CYP phenotype have been developed for some of these enzymes but not for others This proposal examines the value of probe tests of CYP activity in predicting
24
Erythromycin
pharmacokinetics and toxicity of paclitaxel and vinorelbine. Paclitaxel is principally metabolized by CYP2C8 and CYP3A4, and vinorelbine by CYP3A4. The first trial is a dose escalation study of weekly paclitaxel administered on a novel schedule, which is targeted toward older patients with lung or breast cancer. Detailed pharmacokinetic parameters will be correlated with toxicity. In the second phase of the trial, CYP3A4 activity will be measured using the erythromycin breath test (ERMBT), and a novel probe-based assay for CYP2C8 (rosiglitazone) will be pilot tested. Drug metabolism phenotype will be correlated with paclitaxel clearance and toxicity, and a predictive model will be designed and prospectively validated in future studies. CYP2C8 and CYP3A4 genotype-phenotype correlations will also be explored. In the second clinical trial, age-related decline in CYP3A4 activity and its impact on clearance and neutropenia in patients treated with vinorelbine will be evaluated. Again, predictive models will be designed and genotype-phenotype correlations explored. The research projects described form the core of a five-year career development plan for Dr. Elizabeth Dees, an Assistant Professor in the Division of Hematology/Oncology. Her mentor, Dr. Paul Watkins, is a leader in the field of pharmacogenetics and drug metabolism and is the Director of the GCRC. Co-mentor, Dr. Beverly Mitchell, is the applicant's Division Director and is the Associate Director of Lineberger Comprehensive Cancer Center (LCCC). They propose a combined didactic and clinical research experience utilizing the resources of the LCCC to foster Dr. Dees's development into an independent clinician investigator with expertise in pharmacokinetics and phenotyping drug metabolizing enzymes. They have assembled a carefully selected group of collaborators and advisors to assist in the research projects and Dr. Dees's career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEPTIDE MAINTENANCE
PHEROMONES
IN
ENTEROCOCCAL
PLASMID
Principal Investigator & Institution: Buttaro, Bettina A.; Microbiology and Immunology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-APR-2007 Summary: (provided by applicant): Enterococcus faecalis plays a major role in the current antibiotic resistance crisis. It is one of the leading causes of antibiotic-resistant nosocomial infections and, as part of the normal flora of the intestinal tract, also serves as a reservoir of antibiotic resistance genes. Peptide pheromone-induced conjugative plasmid transfer contributes to the spread of these antibiotic resistance genes and of other enterococcal virulence factors. The focus of this research is on the role of peptide signaling in plasmid maintenance, specifically of the tetracycline-resistance plasmid pCF10 in Enterococcus faecalis. The original observations of pheromone signaling in conjugative plasmid biology found that the peptide signal cCF10 produced by plasmidfree recipient cells is used for the induction of conjugative pCF10 transfer. cCF10 is produced at the cell surface and internalized by pCF10-containing donor cells by interaction of the cCF10 receptor with the oligopeptide permease. Once inside the cell cCF10 interacts with intracellular effector molecules to induce conjugation. Recently, we have found a second role, for donor-cell produced cCF10, in maintaining pCF10 in the Enterococcus faecalis cell population. In a donor cell population, cCF10 is also produced and its internalization is required to maintain pCF10 in the apparent absence of conjugation. The maintenance functions occur with a minimum pCF10 replicon construct that is unable to be conjugatively transferred, suggesting the role of cCF10 in pCF10 maintenance is distinct from its role in conjugative transfer. The main goal of the research proposed in this application is to gain a basic understanding of how cCF10 is
Studies
25
affecting pCF10 maintenance. (1) Does cCF10 act as a pheromone in maintenance of pCF10? (2) Are the oligopeptide permease and the cCF10 receptor PrgZ required for efficient transport of cCF10 (produced extracellularly)? (3) What are the basic features of the pCF1 0 replicon? (4) What are the intracellular effector molecules responsible for cCF10-dependent pCF10 maintenance? This will lay the groundwork for future experiments to determine how the same peptide can be used for plasmid maintenance without inducing detectable levels of conjugation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHYSIOLOGICAL IMPORTANCE OF GROWTH HORMONE PULSATILITY Principal Investigator & Institution: Jaffe, Craig A.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): The role of GH pulse pattern has been carefully studied in animals. Extensive data from rodents demonstrate that pulsatile and continuous GH profiles have very different endocrine and metabolic effects. In contrast, the present clinical use of GH in humans is empiric and does not reproduce the normal pulsatile pattern of GH release. Suboptimal responses to GH replacement in children and adults might relate to non-physiological GH profiles obtained by daily subcutaneous GH injections. We have previously shown that GH secretion in humans is gender-specific, with woman having more continuous exposure to GH throughout the day. Moreover, we have demonstrated that woman have higher hepatic CYP3A4 activity than do men and that CYP3A4 activity can be increased or decreased by female (continuous) or male (pulsatile) GH administration. We hypothesize that pulsatile and continuous GH patterns have differential effects on the liver and other peripheral tissues in humans. We predict that continuous GH will increase the activity of CYP3A4 and the expression of hepatic IGF-I whereas the pulsatile GH will more effectively increase muscle IGF-I, muscle protein synthesis, fatty acid oxidation and bone turnover. We will test this hypothesis by administering GH intravenously (iv.) in two different patterns to 15 men and 15 women with GH deficiency. Subjects will be admitted to the GCRC three times for 7 days of control or GH treatment. During the first (control) admission, they will receive an iv. infusion of D5W (control). The order of the second and third admissions will be randomized to receive either iv. GH as a continuous infusion or as 6 boluses given over 20 min every 6 h. Whole body fatty acid and amino acid disposition will be measured using iv infusions of [13C]-palmitate and [2H3]-Ieucine. Percutaneous needle muscle biopsies will be performed and ]GF-I mRNA and protein and [2H3]Ieucine incorporation measured. The effect of each treatment on the liver will determined using measurements of serum IGF-I, erythromycin breath test (CYP3A4) and lipoproteins. The effects on bone will be assessed using markers of bone formation and resorption. A role for STAT as a mediator of pulse-dependent effects of GH will be investigated by quantifying muscle phosphorylated STAT5. Insulin sensitivity will be assessed. The results of this study will add to our understanding of the physiology and pathophysiology of GH action and will help in designing more effective means of GH replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
26
•
Erythromycin
Project Title: PROBING THE SUBSTRATE SPECIFICITY OF POLYKETIDE SYNTHASE Principal Investigator & Institution: Wang, Clay C.; Chemical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 04-FEB-2002 Summary: (provided by applicant) Polyketides are a large family of structurally diverse and complex natural products with a wide range of biological functions. In nature, polyketides are biosynthesized by large polyketide synthase enzymes (PKS) through the successive condensations of simple monomers. The long-term goal of the proposed research is to understand the PKSs in order to generate novel polyketides through bioengineering techniques. For modular PKS, each individual module contains all the necessary active sites to carry on one round of synthesis. The proposed research will express and purify the individual modules of 6 deoxyerythronolide B synthase (DEBS). DEBS is a modular PKS responsible for the biosynthesis of the antibiotic erythromycin. Substrates are designed to specifically probe the underlying rules for binding and processing of different substrates by the individual modules. Native and hybrid bimodular constructs will also be prepared and subjected to the novel substrates to understand the incorporation of the substrates by the first module and transfer to the second module for further chemical transformations. Understanding the substrate specificities of the PKS is an important step towards combinatorial biosynthesis of diverse polyketides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DISORDERS
PSYCHOBIOLOGY
OF
EATING
BEHAVIOR
IN
EATING
Principal Investigator & Institution: Walsh, B T.; Professor; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2004; Project Start 01-JAN-1997; Project End 31-DEC-2008 Summary: (provided by investigator): Bulimia Nervosa (BN) is a serious eating disorder characterized by frequent uncontrolled eating binges. Binge Eating Disorder (BED) is a more recently described disorder which occurs primarily in obese individuals and which is associated with significant morbidity. While much is known about the characteristics and treatment of these disorders, particularly BN, there is as yet a limited understanding of their pathophysiology. The aim of this ongoing research program is to describe objectively the eating behavior of individuals with disorders of binge eating and, using this information, to generate and test hypotheses concerning their pathophysiology. Work to date has focused on the inhibitory controls of eating, i.e., the development of satiety during a meal, and considerable evidence has been obtained suggesting that binge eating in BN and BED reflects a disturbance in these controls. Studies of gastrointestinal function in BN demonstrated abnormalities in gastric emptying, postprandial gastric relaxation, and cholecystokinin (CCK) release, and suggested a physiological model of altered satiety in BN. Other findings suggested a disturbance in the excitatory controls of eating in BN and BED. The proposed project will critically test, both in the laboratory and the clinic, the hypothesis that disturbances in the inhibitory and excitatory controls of eating contribute to behavioral symptoms in BN and BED. Experiments in patients with BN will determine whether the administration of CCK reduces binge eating in a laboratory setting, and whether treatment with erythromycin, an agent that accelerates gastric emptying, enhances CCK release and reduces the frequency of binge eating. Other experiments focusing on BN
Studies
27
will determine whether an increased rate of eating is necessary to produce the increased caloric intake characteristic of binge eating. Experiments focusing on BED will determine whether individuals with this disorder have disturbances in the release of CCK and in gastric emptying similar to those of individuals with BN. Additional experiments will examine whether excitatory controls of eating, as reflected by sham feeding (i.e., consumption of non-caloric food) and by cue reactivity, are increased in patients with BN and BED. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RNA-SPECIFIC LIGANDS: AN APPROACH TO NEW ANTIVIRALS Principal Investigator & Institution: Beal, Peter A.; Associate Professor; Chemistry; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2003 Summary: Ribonucleic acid (RNA) function is central to all life, including that of viruses and bacteria. Antibacterial agents such as neomycin and erythromycin are examples of existing drugs that target sites in bacterial ribosomal RNAs. Unfortunately, bacteria are becoming increasingly resistant to these compounds via adaptation that allows for the modification of the RNA target or modification of the antibiotic. Human immunodeficiency virus (HIV), adenovirus (AV) and Epstein-Barr virus (EBV) are examples of human pathogens that all have unique RNA structures that appear necessary for replication. Each of these RNAs are potential targets for drug intervention. Unfortunately, our lack of understanding of the recognition of RNA by small molecules limits our ability to design high affinity ligands. The goal of this project is to identify low molecular weight ligands (<-l000 Da) that bind selectively to predefined RNA structures and inhibit the formation of protein-RNA complexes. This will be accomplished via the generation of structurally diverse libraries of molecules and the selection of library members with the requisite affinity and selectivity properties. The libraries are designed to contain intercalating ligands with appended functional groups capable of making specific contacts in the grooves of an RNA double helix. These experiments will ultimately lead to the ability to design and synthesize molecules that bind selectively to specific sequences of duplex RNA. In addition, these new compounds would have the potential to be developed into therapeutics for viral and bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SOLID STATE NMR STUDIES OF PEPTIDES AND PROTEINS Principal Investigator & Institution: Griffin, Robert G.; Director; Center for Cancer Research; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-MAY-1977; Project End 31-AUG-2004 Summary: (Adapted from abstract): This proposal focuses on the development of solid state NMR methods for the characterization of 3D structures of proteins and peptides and the accomplishment of those structures. Peptide and protein structure will be demonstrated first with the short peptide MLF and then with protein G. The primary approach will be to use torsional constraints in crystalline samples for the local structure and distances for the long-range constraints. The research will employ innovative isotopic labeling schemes. Complex structures will be characterized with erythromycin/ribosome complex, the ribonucleotide reductase inhibitor complex and characterization of the potential low barrier hydrogen bond in lytic protease. The project with bound EA will dramatically push the limits of solid state NMR sensitivity.
28
Erythromycin
Negative labeling with 2H and 12C as well as the potential of using DNP (dynamic nuclear polarization) are presented. Protein dynamics will be characterized focusing on MLF and protein G, a complete characterization of dynamics in these systems is sought with 15N and 2H lineshapes and 2H relaxation. Method development will occur throughout this project to achieve the necessary goals of sensitivity, selectivity, assignments, and structural constraints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRATEGIES FOR THE SYNTHESIS OF BIOACTIVE TARGETS Principal Investigator & Institution: Martin, Stephen F.; Professor; Chemistry and Biochemistry; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-DEC-1990; Project End 30-JUN-2003 Summary: (Applicant's Abstract) The research program outlined herein is directed toward the design and development of general strategies for the syntheses of natural and unnatural products that exhibit significant biological activity. During the course of these investigations, the scope and limitations of selected reactions and processes will be explored in the context of the total synthesis of complex molecules, and new methods for carbon-carbon bond formation and functional group manipulation will be discovered and developed. The specific objectives include completing the total syntheses of several biologically important natural products including the macrolide antibiotic erythromycin B, the antifungal antibiotic ambruticin, the anticancer agent FR900482, and the squalene synthase inhibitor and antifungal agent zaragozic acid A. The basic strategies for the syntheses of these compounds are unique and involve the stereoselective elaboration of furans and hydropyrans derived therefrom, asymmetric cyclopropanations, ring closing metatheses, and vinylogous aldol reactions. The approach to erythromycin B features a non-biogenetic macrolactonization of a fully glycosylated seco-acid derivative. New biologically active targets have been selected that will serve as the forum for the invention of novel chemistry. For example, a general strategy for the synthesis of C-aryl glycoside antibiotics will be developed that features (4+2) cycloadditions of substituted furans with benzynes followed by the opening of the oxabicycloheptene adducts thus produced with glycosyl anions. The utility of the approach will then be demonstrated by its application to the synthesis of the anticancer agent rubiflavin A as well as other representative C-aryl glycosides such as galtamycinone. Quantities of the natural products and selected congeners will be prepared for submission to C. P. Starks, Inc., Eli Lilly Company, Merck, Abbott Laboratories, Pfizer, and GlaxoWellcome for biological evaluation as potential antibiotics and as antifungal, hypocholesterolemic and anticancer agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SYNTHESIS POLYPROPIONATES
OF
THE
TEDANOLIDES,
CYTOTOXIC
Principal Investigator & Institution: Jung, Michael E.; Professor; Chemistry and Biochemistry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 16-DEC-1996; Project End 30-NOV-2003 Summary: (Applicant's Abstract) The purpose of this proposed research program is to develop new general methods for the construction of several biologically active polypropionate natural products. The key step in the syntheses of these compounds involves a concerted Lewis acid-promoted rearrangement of an optically active epoxy
Studies
29
alcohol to generate a 2-methyl-3-trialkylsilyloxyalkanal, namely an aldol product by a non-aldol route. We have shown that all four possible enantiomers can be easily prepared in high optical purity and good yields by this approach. We plan to extend this research to prepare polypropionate chains with various absolute stereochemistries. In particular, in order to illustrate the efficiency of this process, we will finish the synthesis of two extremely strongly cytotoxic agents, 13-deoxytedanolide 1 and tedanolide 2, and their close structural analogues, by an application of this new approach to polypropionates. 13-Deoxytedanolide is extremely cytotoxic (IC50 94 pg/ml (P388)) and has high antitumor activity (T/C 189 percent (P388) at 125 microg/kg) while tedanolide is also extremely tumor inhibitory (ED50's 250 pg/ml (KB) and 16 pg/ml (PS)) and causes accumulation of cells in the S phase at very low concentrations (10 ng/ml). Thus they are very promising leads as new agents for cancer treatment. The development of good general routes for their synthesis would not only provide a potentially useful preparation of them (both were isolated from marine sponges and are present in very small quantities) but also would allow one to prepare several structural analogues unavailable from natural sources which may show enhanced chemotherapeutic properties. We will also carry out total syntheses of the important antibacterial agents, erythromycin A 3 and oleandomycin 4. All of the advanced synthetic materials in the tedanolide series will be tested for antitumor activity. In this way, we hope to figure out just what parts of these complex molecules are required for the potent activity and hopefully to prepare some simpler structures which still show reasonable activity. Likewise the synthetic analogues of erythromycin and oleandomycin will be tested for antibiotic activity. The successful accomplishment of the research described in this proposal-namely, the development of a really useful synthetic route to polypropionates and the synthesis of the tedanolides, erythromycin A and oleandomycin and their analogues-would be of great significance to medicinal chemistry. Because of the medicinal importance of the targets, the efficiency of bond construction in the syntheses, and the high intrinsic value of the new methods themselves, the likelihood of an important contribution to health-related science is quite high. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UAB/AKU GLOBAL NETWORK RESEARCH UNIT Principal Investigator & Institution: Goldenberg, Robert L.; Professor; Obstetrics and Gynecology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 03-SEP-2001; Project End 30-APR-2006 Summary: We will develop a University of Alabama at Birmingham-Aga Khan University multidisciplinary research team with its major goal the reduction of infection-related perinatal mortality in Pakistan. To accomplish this goal, we will continue to build the UAB-AKU research relationship around a series of studies on perinatal infection and pregnancy outcome. The first study will characterize two populations of Pakistani pregnant women. A cohort study consisting of 1500 urban and later 1500 rural women will be performed in which data will be collected near midpregnancy on infections such as bacterial vaginosis, gonorrhea and chlamydia, and on various pregnancy-associated cervicovaginal and serum markers of infections. These data will be correlated with pregnancy outcome. We will also collect psychosocial, nutritional, medical and dental data and correlate these results with bacterial infection of the vagina, the infection markers and with pregnancy outcome. The goal of this study is 1) to determine the current pregnancy outcomes in two Pakistani populations, 2) to determine the prevalence of vaginal infections and markers of infection in these two populations, and 3) to determine the prevalence of various psychosocial, nutritional,
30
Erythromycin
medical and dental factors associated with vaginal infection, markers of infection and adverse pregnancy outcomes. Upon completion of the urban cohort study, women identified as high risk for perinatal death because of a previous perinatal death will be invited to participate in a randomized trial of prenatal and perinatal antibiotics to reduce infection-related perinatal mortality. In this study, women who have had a previous stillbirth or a neonatal death will be randomized to one week of treatment with metronidazole and erythromycin or placebos in the late second trimester, with a repeat course of antibiotics or placebo in labor. The primary endpoint will be perinatal mortality. Our second attempt to decrease infection-related mortality will be in a randomized trial of an intrapartum and infant chlorhexidine wash versus placebo washes with saline. With the completion of these projects, not only will we have answered some very important questions related to infections and pregnancy outcome, but AKU, in partnership with UAB, will have developed superb rural and urban pregnancy-related research infrastructures tightly linked to their developing maternity health care systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE OF ERYTHROMYCIN BREATH TEST TO EVALUATE HEPATIC CY3A4 ACTIVITY Principal Investigator & Institution: Pollk, Ron E.; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: VARIABILITY IN ESTROGEN METABOLISM POSTMENOPAUSE Principal Investigator & Institution: Goldner, Deborah N.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: X-RAY STUDIES OF SUGAR-MODIFYING ENZYMES Principal Investigator & Institution: Holden, Hazel M.; Professor; Institute for Enzyme Research; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUN-1994; Project End 31-MAY-2006 Summary: Nucleotide-linked sugars are found in all organisms where they fulfill a variety of important biological roles. In galactose metabolism, which has been one of the main focuses of this laboratory for twelve years, the sugar is attached to UDP. Interestingly, many of the deoxysugars, which display wide ranges of biological activities from mediating cell-cell interactions to serving as components in various antibiotics, are synthesized via biochemical pathways starting with the attachment of alpha-D-glucose-1 phosphate to either CDP or TDP. The overall goal of this grant renewal is to understand by x-ray crystallographic and site-directed mutagenesis techniques, the structures of enzymes that specific modify nucleotide-linked sugars. The systems that will be investigated include human UDP-galactose 4-epimerase, CDP-Dtyvelose 2-epimerase from Y. pseudotuberculosis IVA, 2,3-d4ehydratase from S. fradiae, and seven enzymes isolated from S. venezuelae that are involved in the biosynthesis of
Studies
31
desosamine. UDP-galactose 4-epimerase functions in galactose metabolism by catalyzing the interconversion of UDP-galactose and UDP-glucose. CDP-tyvelose. Tyvelose occurs in the O-antigens of some types of gram-negative bacteria. These 2,3dehydratase to be studied catalyzes the first step in mycarose biosynthesis. Both mycarose and desosamine are deoxysugars found in some macrolide antibiotics such as erythromycin. The research on UDP-galactose 4-epimerase is in its final stage. The proposed studies on enzymes involved deoxysugars biosynthesis are completely new. Ultimately new structural analysis will yield detailed three-dimensional descriptions of protein: ligand interactions and may eventually provide a molecular foundation upon which to base the design of new antimicrobial agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “erythromycin” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for erythromycin in the PubMed Central database: •
A New Ketolide, HMR 3004, Active against Streptococci Inducibly Resistant to Erythromycin. by Rosato A, Vicarini H, Bonnefoy A, Chantot JF, Leclercq R.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105610
•
A Novel Efflux System in Inducibly Erythromycin-Resistant Strains of Streptococcus pyogenes. by Giovanetti E, Brenciani A, Burioni R, Varaldo PE.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132784
•
A Novel Erythromycin Resistance Methylase Gene (ermTR) in Streptococcus pyogenes. by Seppala H, Skurnik M, Soini H, Roberts MC, Huovinen P.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105397
•
A Point Mutation Associated with Bacterial Macrolide Resistance Is Present in Both 23S rRNA Genes of an Erythromycin-Resistant Treponema pallidum Clinical Isolate. by Stamm LV, Bergen HL.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89774
•
A Serotype V Clone Is Predominant among Erythromycin-Resistant Streptococcus agalactiae Isolates in a Southwestern Region of Germany. by von Both U, Ruess M, Mueller U, Fluegge K, Sander A, Berner R.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154707
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
32
Erythromycin
•
A Simplified Method for Testing Bordetella pertussis for Resistance to Erythromycin and Other Antimicrobial Agents. by Hill BC, Baker CN, Tenover FC.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86361
•
Activities of a New Fluoroketolide, HMR 3787, and Its (Des)-Fluor Derivative RU 64399 Compared to Those of Telithromycin, Erythromycin A, Azithromycin, Clarithromycin, and Clindamycin against Macrolide-Susceptible or -Resistant Streptococcus pneumoniae and S. pyogenes. by Nagai K, Davies TA, Ednie LM, Bryskier A, Palavecino E, Jacobs MR, Appelbaum PC.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90817
•
Activities of HMR 3004 (RU 64004) and HMR 3647 (RU 66647) Compared to Those of Erythromycin, Azithromycin, Clarithromycin, Roxithromycin, and Eight Other Antimicrobial Agents against Unusual Aerobic and Anaerobic Human and Animal Bite Pathogens Isolated from Skin and Soft Tissue Infections in Humans. by Goldstein EJ, Citron DM, Gerardo SH, Hudspeth M, Merriam CV.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105757
•
Activities of Telithromycin (HMR 3647, RU 66647) Compared to Those of Erythromycin, Azithromycin, Clarithromycin, Roxithromycin, and Other Antimicrobial Agents against Unusual Anaerobes. by Goldstein EJ, Citron DM, Merriam CV, Warren Y, Tyrrell K.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89565
•
Activity of A-56268 compared with that of erythromycin and other oral agents against aerobic and anaerobic bacteria. by Chin NX, Neu NM, Labthavikul P, Saha G, Neu HC.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174754
•
Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives. by Ruan X, Pereda A, Stassi DL, Zeidner D, Summers RG, Jackson M, Shivakumar A, Kakavas S, Staver MJ, Donadio S, Katz L.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179558
•
An Erythromycin Analog Produced by Reprogramming of Polyketide Synthesis. by Donadio S, McAlpine JB, Sheldon PJ, Jackson M, Katz L.; 1993 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47087
•
Analysis of an 8.1-kb DNA Fragment Contiguous with the Erythromycin Gene Cluster of Saccharopolyspora erythraea in the eryCI-Flanking Region. by Reeves AR, Weber G, Cernota WH, Weber JM.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132777
•
Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II. by Arthur M, Autissier D, Courvalin P.; 1986 Jun 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311505
•
Antibacterial activities of erythromycins A, B, C, and D and some of their derivatives. by Kibwage IO, Hoogmartens J, Roets E, Vanderhaeghe H, Verbist L, Dubost M, Pascal C, Petitjean P, Levol G.; 1985 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176346
Studies
33
•
Antibacterial Effects of Levofloxacin, Erythromycin, and Rifampin in a Human Monocyte System against Legionella pneumophila. by Baltch AL, Smith RP, Franke MA, Michelsen PB.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106015
•
Antibiotic Susceptibility and Mechanisms of Erythromycin Resistance in Clinical Isolates of Streptococcus agalactiae: French Multicenter Study. by De Mouy D, Cavallo JD, Leclercq R, Fabre R.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90666
•
Autobacteriographic studies of clarithromycin and erythromycin in mice. by Kohno Y, Ohta K, Suwa T, Suga T.; 1990 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171644
•
Bacteriostatic and Bactericidal In Vitro Activities of Clarithromycin and Erythromycin against Periodontopathic Actinobacillus actinomycetemcomitans. by Piccolomini R, Catamo G, Di Bonaventura G.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105980
•
Bordetella pertussis Isolates with a Heterogeneous Phenotype for Erythromycin Resistance. by Wilson KE, Cassiday PK, Popovic T, Sanden GN.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120648
•
Can Etest Be Used To Determine Vibrio cholerae Susceptibility to Erythromycin? by Ng LK, Sawatzky P.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152522
•
Characterization of erythromycin resistance in Campylobacter jejuni and Campylobacter coli. by Yan W, Taylor DE.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245313
•
Characterization of Erythromycin-Resistant Isolates of Staphylococcus aureus Recovered in the United States from 1958 through 1969. by Nicola FG, McDougal LK, Biddle JW, Tenover FC.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105988
•
Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions of Pseudomonas aeruginosa pigments with human neutrophils in vitro. by Ras GJ, Anderson R, Taylor GW, Savage JE, van Niekerk E, Joone G, Koornhof HJ, Saunders J, Wilson R, Cole PJ.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190324
•
Comparative activities of clarithromycin, erythromycin, and azithromycin against penicillin-susceptible and penicillin-resistant pneumococci. by Ednie LM, Visalli MA, Jacobs MR, Appelbaum PC.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163449
•
Comparative in vitro activities of clarithromycin, azithromycin, and erythromycin against Borrelia burgdorferi. by Dever LL, Jorgensen JH, Barbour AG.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188047
•
Comparative In Vitro Activities of Linezolid, Quinupristin-Dalfopristin, Moxifloxacin, and Trovafloxacin against Erythromycin-Susceptible and -Resistant
34
Erythromycin
Streptococci. by Betriu C, Redondo M, Palau ML, Sanchez A, Gomez M, Culebras E, Boloix A, Picazo JJ.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89970 •
Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats. by Kohno Y, Yoshida H, Suwa T, Suga T.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172527
•
Comparison of Pharmacodynamics of Azithromycin and Erythromycin In Vitro and In Vivo. by den Hollander JG, Knudsen JD, Mouton JW, Fuursted K, Frimodt-Moller N, Verbrugh HA, Espersen F.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105417
•
Comparison of the effects of the new azalide antibiotic, azithromycin, and erythromycin estolate on rat liver cytochrome P-450. by Amacher DE, Schomaker SJ, Retsema JA.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284308
•
Comparison of the intracellular activities of clarithromycin and erythromycin against Mycobacterium avium complex strains in J774 cells and in alveolar macrophages from human immunodeficiency virus type 1-infected individuals. by Yajko DM, Nassos PS, Sanders CA, Gonzalez PC, Hadley WK.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188858
•
Concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms in plasma and tonsillar tissue after repeated dosage of erythromycin stearate and erythromycin acistrate. by Gordin A, Mannisto PT, Antikainen R, Savolainen S, Ylikoski J, Kokkonen P, Rauramaa V.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172336
•
Contribution of two different mechanisms to erythromycin resistance in Escherichia coli. by Arthur M, Courvalin P.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176516
•
Detection of Tn917-Like Sequences within a Tn916-like Conjugative Transposon (Tn3872) in Erythromycin-Resistant Isolates of Streptococcus pneumoniae. by McDougal LK, Tenover FC, Lee LN, Rasheed JK, Patterson JE, Jorgensen JH, LeBlanc DJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105825
•
Different Erythromycin Resistance Mechanisms in Group C and Group G Streptococci. by Kataja J, Seppala H, Skurnik M, Sarkkinen H, Huovinen P.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105628
•
Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin. by Bailly S, Pocidalo JJ, Fay M, Gougerot-Pocidalo MA.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245317
Studies
35
•
Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci. by Montanari MP, Mingoia M, Giovanetti E, Varaldo PE.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87930
•
Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin. by Tateda K, Ishii Y, Matsumoto T, Furuya N, Nagashima M, Matsunaga T, Ohno A, Miyazaki S, Yamaguchi K.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163517
•
Dissemination of Clonally Unrelated Erythromycin- and Glycopeptide-Resistant Enterococcus faecium Isolates in a Tertiary Greek Hospital. by Maniatis AN, Pournaras S, Kanellopoulou M, Kontos F, Dimitroulia E, Papafrangas E, Tsakris A.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88591
•
Dissemination of High-Level Penicillin-, Extended-Spectrum Cephalosporin-, and Erythromycin-Resistant Streptococcus pneumoniae Clones in Taiwan. by Hsueh PR, Teng LJ, Lee LN, Yang PC, Ho SW, Luh KT.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84215
•
Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains. by Dagan R, Bar-David Y.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188356
•
Effect of CO2 on susceptibilities of anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin. by Spangler SK, Jacobs MR, Appelbaum PC.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284428
•
Effects of erythromycin and ciprofloxacin on chronic fecal excretion of Campylobacter species in marmosets. by Goodman LJ, Kaplan RL, Petrak RM, Fliegelman RM, Taff D, Walton F, Penner JL, Trenholme GM.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176374
•
Effects of roxithromycin and erythromycin on interleukin 8-induced neutrophil recruitment and goblet cell secretion in guinea pig tracheas. by Tamaoki J, Nakata J, Tagaya E, Konno K.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163405
•
Effects of topical erythromycin on ecology of aerobic cutaneous bacterial flora. by Vowels BR, Feingold DS, Sloughfy C, Foglia AN, Konnikov N, Ordoukhanian E, Starkey P, Leyden JJ.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163583
•
Effects of two oral erythromycin ethylsuccinate formulations on the motility of the small intestine in human beings. by Caron F, Bouaniche M, Delatour F, Ducrotte P, Torlotin JC, Denis P, Humbert G, Rouveix B.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163419
36
Erythromycin
•
Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice. by Hirakata Y, Kaku M, Tomono K, Tateda K, Furuya N, Matsumoto T, Araki R, Yamaguchi K.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190317
•
Emergence of Erythromycin-Resistant, Clindamycin-Susceptible Streptococcus pyogenes Isolates in Madrid, Spain. by Garcia-Bermejo I, Cacho J.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105590
•
emm Gene Distribution among Erythromycin-Resistant and -Susceptible Italian Isolates of Streptococcus pyogenes. by Zampaloni C, Cappelletti P, Prenna M, Vitali LA, Ripa S.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150311
•
Erythromycin and azithromycin transport into Haemophilus influenzae ATCC 19418 under conditions of depressed proton motive force (delta mu H). by Capobianco JO, Goldman RC.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171926
•
Erythromycin and Clindamycin Resistance and Telithromycin Susceptibility in Streptococcus agalactiae. by Betriu C, Culebras E, Gomez M, Rodriguez-Avial I, Sanchez BA, Agreda MC, Picazo JJ.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149330
•
Erythromycin bioactivity is stable in ophthalmic ointment used for prophylaxis of neonatal gonococcal conjunctivitis. by Bialer MG, Baron EJ, Harper RG.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284221
•
Erythromycin Inhibits Transcriptional Activation of NF-[kappa]B, but not NFAT, through Calcineurin-Independent Signaling in T Cells. by Aoki Y, Kao PN.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89542
•
Erythromycin Inhibits Tumor Necrosis Factor Alpha and Interleukin 6 Production Induced by Heat-Killed Streptococcus pneumoniae in Whole Blood. by Schultz MJ, Speelman P, Zaat S, van Deventer SJ, van der Poll T.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105654
•
Erythromycin Modulates Eosinophil Chemotactic Cytokine Production by Human Lung Fibroblasts in Vitro. by Sato E, Nelson DK, Koyama S, Hoyt JC, Robbins RA.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90304
•
Erythromycin Resistance Genes in Group A Streptococci in Finland. by Kataja J, Huovinen P, Skurnik M, Seppala H.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89019
•
Erythromycin Resistance in Borrelia burgdorferi. by Terekhova D, Sartakova ML, Wormser GP, Schwartz I, Cabello FC.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128697
•
Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance. by Fass RJ.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192232
Studies
37
•
Erythromycin-Resistant Group A Streptococcal Isolates Recovered in Sofia, Bulgaria, from 1995 to 2001. by Detcheva A, Facklam RR, Beall B.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130905
•
Erythromycin-Resistant Neisseria gonorrhoeae and Oral Commensal Neisseria spp. Carry Known rRNA Methylase Genes. by Roberts MC, Chung WO, Roe D, Xia M, Marquez C, Borthagaray G, Whittington WL, Holmes KK.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89280
•
Erythromycin-Resistant Pharyngeal Isolates of Streptococcus pyogenes Recovered in Italy. by Dicuonzo G, Fiscarelli E, Gherardi G, Lorino G, Battistoni F, Landi S, De Cesaris M, Petitti T, Beall B.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132735
•
Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering. by Stassi DL, Kakavas SJ, Reynolds KA, Gunawardana G, Swanson S, Zeidner D, Jackson M, Liu H, Buko A, Katz L.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22598
•
Evaluation of in vitro spectra of activity of azithromycin, clarithromycin, and erythromycin tested against strains of Neisseria gonorrhoeae by reference agar dilution, disk diffusion, and Etest methods. by Mehaffey PC, Putnam SD, Barrett MS, Jones RN.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228828
•
Evaluation of three 4"-deoxy-4"-sulfonamido-oleandomycin derivatives with erythromycin-like antibacterial potency. by English AR, Retsema JA, Girard AE, Schelkly W, Lynch JE.; 1984 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185447
•
Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants. by Baier RJ, Loggins J, Kruger TE.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=212466
•
Flow Cytometric Assessment of Susceptibilities of Streptococcus pyogenes to Erythromycin and Rokitamycin. by Braga PC, Bovio C, Culici M, Dal Sasso M.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148962
•
Fluorescent Assay for Estimating the Binding of Erythromycin Derivatives to Ribosomes. by Brandt-Rauf P, Vince R, LeMahieu R, Pestka S.; 1978 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352409
•
Genotypic Identification of Erythromycin-Resistant Campylobacter Isolates as Helicobacter Species and Analysis of Resistance Mechanism. by Kuijper EJ, Stevens S, Imamura T, de Wever B, Claas EC.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179794
•
High Incidence of Erythromycin Resistance among Clinical Isolates of Streptococcus agalactiae in Taiwan. by Hsueh PR, Teng LJ, Lee LN, Ho SW, Yang PC, Luh KT.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90806
38
Erythromycin
•
High Prevalence of Inducible Erythromycin Resistance among Streptococcus bovis Isolates in Taiwan. by Teng LJ, Hsueh PR, Ho SW, Luh KT.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90838
•
High rate of erythromycin and clarithromycin resistance among Streptococcus pneumoniae isolates from blood cultures from Providence, R.I. by Lonks JR, Medeiros AA.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188063
•
Identification of a Mutation Associated with Erythromycin Resistance in Bordetella pertussis: Implications for Surveillance of Antimicrobial Resistance. by Bartkus JM, Juni BA, Ehresmann K, Miller CA, Sanden GN, Cassiday PK, Saubolle M, Lee B, Long J, Harrison, Jr. AR, Besser JM.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150313
•
Identification of an erm(A) Erythromycin Resistance Methylase Gene in Streptococcus pneumoniae Isolated in Greece. by Syrogiannopoulos GA, Grivea IN, Tait-Kamradt A, Katopodis GD, Beratis NG, Sutcliffe J, Appelbaum PC, Davies TA.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90289
•
Importance of Local Variations in Antibiotic Consumption and Geographical Differences of Erythromycin and Penicillin Resistance in Streptococcus pneumoniae. by Garcia-Rey C, Aguilar L, Baquero F, Casal J, Dal-Re R.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120130
•
In vitro activities of azithromycin (CP 62,993), clarithromycin (A-56268; TE-031), erythromycin, roxithromycin, and clindamycin. by Barry AL, Jones RN, Thornsberry C.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172265
•
In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae. by Welsh L, Gaydos C, Quinn TC.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163084
•
In Vitro Activities of the Novel Ketolide Telithromycin (HMR 3647) against Erythromycin-Resistant Streptococcus Species. by Jalava J, Kataja J, Seppala H, Huovinen P.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90375
•
In vitro activity and in vivo efficacy of a new series of 9-deoxo-12-deoxy-9,12epoxyerythromycin A derivatives. by Hardy DJ, Swanson RN, Shipkowitz NL, Freiberg LA, Lartey PA, Clement JJ.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245130
•
In vitro activity of a new macrolide, A-56268, compared with that of roxithromycin, erythromycin, and clindamycin. by Barry AL, Thornsberry C, Jones RN.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174723
Studies
39
•
In vitro activity of A-56268 (TE-031), a new macrolide antibiotic, compared with that of erythromycin and other antimicrobial agents. by Floyd-Reising S, Hindler JA, Young LS.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174797
•
In vitro activity of A-56268 (TE-031), a new macrolide, compared with that of erythromycin and clindamycin against selected gram-positive and gram-negative organisms. by Benson CA, Segreti J, Beaudette FE, Hines DW, Goodman LJ, Kaplan RL, Trenholme GM.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174717
•
In vitro activity of azithromycin compared with that of erythromycin against Actinobacillus actinomycetemcomitans. by Pajukanta R, Asikainen S, Saarela M, Alaluusua S, Jousimies-Somer H.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190325
•
In vitro evaluation of activities of azithromycin, erythromycin, and tetracycline against Chlamydia trachomatis and Chlamydia pneumoniae. by Welsh LE, Gaydos CA, Quinn TC.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188358
•
In vitro evaluation of CP-62,993, erythromycin, clindamycin, and tetracycline against Chlamydia trachomatis. by Walsh M, Kappus EW, Quinn TC.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174839
•
In Vitro Induction of Resistance to Erythromycin by Its Metabolite. by Majer J.; 1981 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181491
•
In Vitro Susceptibilities of Bordetella pertussis and Bordetella parapertussis to Two Ketolides (HMR 3004 and HMR 3647), Four Macrolides (Azithromycin, Clarithromycin, Erythromycin A, and Roxithromycin), and Two Ansamycins (Rifampin and Rifapentine). by Hoppe JE, Bryskier A.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105582
•
In vitro susceptibilities of Campylobacter jejuni and Campylobacter coli to azithromycin and erythromycin. by Taylor DE, Chang N.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245292
•
In vitro susceptibilities of Entamoeba histolytica to azithromycin, CP-63,956, erythromycin, and metronidazole. by Ravdin JI, Skilogiannis J.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284263
•
In vivo efficacy of azithromycin in treatment of systemic infection and septic arthritis induced by type IV group B Streptococcus strains in mice: comparative study with erythromycin and penicillin G. by Tissi L, von Hunolstein C, Mosci P, Campanelli C, Bistoni F, Orefici G.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162860
40
Erythromycin
•
Inactivation of the macrolide antibiotics erythromycin, midecamycin, and rokitamycin by pathogenic Nocardia species. by Yazawa K, Mikami Y, Sakamoto T, Ueno Y, Morisaki N, Iwasaki S, Furihata K.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284711
•
Influence of etoposide and cyclophosphamide on the efficacy of cloxacillin and erythromycin in an experimental staphylococcal infection. by Calame W, van der Waals R, Mattie H, van Furth R.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284270
•
Influence of food on absorption of erythromycin ethyl succinate. by Thompson PJ, Burgess KR, Marlin GE.; 1980 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284098
•
Influence of study design in assessing food effects on absorption of erythromycin base and erythromycin stearate. by DiSanto AR, Chodos DJ.; 1981 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181662
•
Inhibitory Effect of Erythromycin on Superoxide Anion Production by Human Neutrophils Primed with Granulocyte-Colony Stimulating Factor. by Kadota JI, Iwashita T, Matsubara Y, Ishimatsu Y, Yoshinaga M, Abe K, Kohno S.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105700
•
Interactions of Ofloxacin and Erythromycin with the Multidrug Resistance Protein (MRP) in MRP-Overexpressing Human Leukemia Cells. by Terashi K, Oka M, Soda H, Fukuda M, Kawabata S, Nakatomi K, Shiozawa K, Nakamura T, Tsukamoto K, Noguchi Y, Suenaga M, Tei C, Kohno S.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89936
•
Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin. by Conte JE Jr, Golden JA, Duncan S, McKenna E, Zurlinden E.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162537
•
Lack of Synergy of Erythromycin Combined with Penicillin or Cefotaxime against Streptococcus pneumoniae In Vitro. by Lin E, Stanek RJ, Mufson MA.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149295
•
mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae. by Tait-Kamradt A, Clancy J, Cronan M, Dib-Hajj F, Wondrack L, Yuan W, Sutcliffe J.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164101
•
MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin-susceptible and -resistant pneumococci. by Pankuch GA, Jacobs MR, Appelbaum PC.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163475
Studies
41
•
Microbial glycosylation of erythromycin A. by Kuo MS, Chirby DG, Argoudelis AD, Cialdella JI, Coats JH, Marshall VP.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172826
•
Molecular Epidemiology of Erythromycin Resistance in Streptococcus pneumoniae Isolates from Blood and Noninvasive Sites. by Amezaga MR, Carter PE, Cash P, McKenzie H.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130757
•
Molecular Investigation of the Postantibiotic Effects of Clarithromycin and Erythromycin on Staphylococcus aureus Cells. by Champney WS, Tober CL.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89272
•
Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products. by McDaniel R, Thamchaipenet A, Gustafsson C, Fu H, Betlach M, Betlach M, Ashley G.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26699
•
Mutation and cloning of eryG, the structural gene for erythromycin Omethyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli. by Paulus TJ, Tuan JS, Luebke VE, Maine GT, DeWitt JP, Katz L.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208895
•
Mutations in 23S rRNA in Helicobacter pylori Conferring Resistance to Erythromycin Do Not Always Confer Resistance to Clarithromycin. by Garcia-Arata MI, Baquero F, de Rafael L, de Argila CM, Gisbert JP, Bermejo F, Boixeda D, Canton R.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89082
•
Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis. by Lampson BC, von David W, Parisi JT.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176508
•
Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea. by Weber JM, Leung JO, Maine GT, Potenz RH, Paulus TJ, DeWitt JP.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208872
•
Pharmacoepidemiological Analysis of Provincial Differences between Consumption of Macrolides and Rates of Erythromycin Resistance among Streptococcus pyogenes Isolates in Spain. by Garcia-Rey C, Aguilar L, Baquero F, Casal J, Martin JE.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120652
•
Pharmacokinetic advantages of erythromycin estolate over ethylsuccinate as determined by high-pressure liquid chromatography. by Croteau D, Bergeron MG, LeBel M.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172220
•
Pharmacokinetics of erythromycin ethylsuccinate and estolate in infants under 4 months of age. by Patamasucon P, Kaojarern S, Kusmiesz H, Nelson JD.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181514
42
Erythromycin
•
Pharmacokinetics of single-dose erythromycin in normal and alcoholic liver disease subjects. by Kroboth PD, Brown A, Lyon JA, Kroboth FJ, Juhl RP.; 1982 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181841
•
Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy. by Montanari MP, Mingoia M, Cochetti I, Varaldo PE.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149635
•
Phenotypes and Genotypes of Erythromycin-Resistant Streptococcus pyogenes Strains in Italy and Heterogeneity of Inducibly Resistant Strains. by Giovanetti E, Montanari MP, Mingoia M, Varaldo PE.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89394
•
Phenotypic and Molecular Characterization of Tetracycline- and ErythromycinResistant Strains of Streptococcus pneumoniae. by Montanari MP, Cochetti I, Mingoia M, Varaldo PE.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161878
•
Plasma bactericidal activity after administration of erythromycin estolate and erythromycin ethylsuccinate to healthy volunteers. by Berube D, Kirouac D, Croteau D, Bergeron MG, Lebel M.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172382
•
Postantibiotic Effect and Postantibiotic Sub-MIC Effect of Levofloxacin Compared to Those of Ofloxacin, Ciprofloxacin, Erythromycin, Azithromycin, and Clarithromycin against 20 Pneumococci. by Spangler SK, Lin G, Jacobs MR, Appelbaum PC.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105793
•
Postantibiotic Suppression of Growth of Erythromycin A-Susceptible and -Resistant Gram-Positive Bacteria by the Ketolides Telithromycin (HMR 3647) and HMR 3004. by Munckhof WJ, Borlace G, Turnidge JD.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89952
•
Presence of the tet(O) Gene in Erythromycin- and Tetracycline-Resistant Strains of Streptococcus pyogenes and Linkage with either the mef(A) or the erm(A) Gene. by Giovanetti E, Brenciani A, Lupidi R, Roberts MC, Varaldo PE.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182639
•
Prevalence of Polyclonal mefA-Containing Isolates among Erythromycin-Resistant Group A Streptococci in Southern Taiwan. by Yan JJ, Wu HM, Huang AH, Fu HM, Lee CT, Wu JJ.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86946
•
Prospective open randomized study comparing efficacies and safeties of a 3-day course of azithromycin and a 10-day course of erythromycin in children with community-acquired acute lower respiratory tract infections. by Roord JJ, Wolf BH, Gossens MM, Kimpen JL.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163618
•
Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo. by Goldfarb J, Crenshaw D, O'Horo J, Lemon E, Blumer JL.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176017
Studies
43
•
Reaction of roxithromycin and clarithromycin with macrolide-inactivating enzymes from highly erythromycin-resistant Escherichia coli. by O'Hara K, Yamamoto K.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163256
•
Ribosomal protein gene sequence changes in erythromycin-resistant mutants of Escherichia coli. by Chittum HS, Champney WS.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=196958
•
Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. by Oishi K, Sonoda F, Kobayashi S, Iwagaki A, Nagatake T, Matsushima K, Matsumoto K.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303089
•
Serotype 19F Multiresistant Pneumococcal Clone Harboring Two Erythromycin Resistance Determinants [erm(B) and mef(A)] in South Africa. by McGee L, Klugman KP, Wasas A, Capper T, Brink A.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90516
•
Spontaneous Erythromycin Resistance Mutation in a 23S rRNA Gene, rrlA, of the Extreme Thermophile Thermus thermophilus IB-21. by Gregory ST, Cate JH, Dahlberg AE.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95329
•
Survey of emm Gene Sequences from Pharyngeal Streptococcus pyogenes Isolates Collected in Spain and Their Relationship with Erythromycin Susceptibility. by Alberti S, Garcia-Rey C, Dominguez MA, Aguilar L, Cercenado E, Gobernado M, Garcia-Perea A.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156550
•
Susceptibilities of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin by oxyrase agar dilution and E test methodologies. by Spangler SK, Jacobs MR, Appelbaum PC.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228167
•
Susceptibilities of Campylobacter jejuni Isolates from Germany to Ciprofloxacin, Moxifloxacin, Erythromycin, Clindamycin, and Tetracycline. by Wagner J, Jabbusch M, Eisenblatter M, Hahn H, Wendt C, Ignatius R.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161846
•
Susceptibilities of Penicillin- and Erythromycin-Susceptible and -Resistant Pneumococci to HMR 3647 (RU 66647), a New Ketolide, Compared with Susceptibilities to 17 Other Agents. by Pankuch GA, Visalli MA, Jacobs MR, Appelbaum PC.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105509
•
Susceptibilities to clarithromycin and erythromycin of isolates of Chlamydia pneumoniae from children with pneumonia. by Roblin PM, Montalban G, Hammerschlag MR.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284597
44
Erythromycin
•
Susceptibility of bite wound bacteria to seven oral antimicrobial agents, including RU-985, a new erythromycin: considerations in choosing empiric therapy. by Goldstein EJ, Citron DM, Vagvolgyi AE, Finegold SM.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180440
•
Susceptibility of penicillin-susceptible and -resistant pneumococci to dirithromycin compared with susceptibilities to erythromycin, azithromycin, clarithromycin, roxithromycin, and clindamycin. by Visalli MA, Jacobs MR, Appelbaum PC.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164026
•
Synthesis and antimicrobial evaluation of dirithromycin (AS-E 136; LY237216), a new macrolide antibiotic derived from erythromycin. by Counter FT, Ensminger PW, Preston DA, Wu CY, Greene JM, Felty-Duckworth AM, Paschal JW, Kirst HA.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284297
•
The Macrolide Efflux Genetic Assembly of Streptococcus pneumoniae Is Present in Erythromycin-Resistant Streptococcus salivarius. by Stadler C, Teuber M.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128751
•
Tight binding of clarithromycin, its 14-(R)-hydroxy metabolite, and erythromycin to Helicobacter pylori ribosomes. by Goldman RC, Zakula D, Flamm R, Beyer J, Capobianco J.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284582
•
Toxicity, uptake, and subcellular distribution in rat hepatocytes of roxithromycin, a new semisynthetic macrolide, and erythromycin base. by Villa P, Sassella D, Corada M, Bartosek I.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175915
•
Transcriptional Organization of the Erythromycin Biosynthetic Gene Cluster of Saccharopolyspora erythraea. by Reeves AR, English RS, Lampel JS, Post DA, Vanden Boom TJ.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94186
•
Transfer of Erythromycin Resistance from Poultry to Human Clinical Strains of Staphylococcus aureus. by Khan SA, Nawaz MS, Khan AA, Cerniglia CE.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86602
•
Transformation of Rickettsia prowazekii to Erythromycin Resistance Encoded by the Escherichia coli ereB Gene. by Rachek LI, Hines A, Tucker AM, Winkler HH, Wood DO.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94521
•
Transition mutations in the 23S rRNA of erythromycin-resistant isolates of Mycoplasma pneumoniae. by Lucier TS, Heitzman K, Liu SK, Hu PC.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163027
•
Uptake, accumulation, and egress of erythromycin by tissue culture cells of human origin. by Martin JR, Johnson P, Miller MF.; 1985 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176268
Studies
45
•
Vancomycin Tolerance Induced by Erythromycin but Not by Loss of vncRS, vex3, or pep27 Function in Streptococcus pneumoniae. by Robertson GT, Zhao J, Desai BV, Coleman WH, Nicas TI, Gilmour R, Grinius L, Morrison DA, Winkler ME.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135460
•
Variability of clarithromycin and erythromycin susceptibility tests with Haemophilus influenzae in four different broth media and correlation with the standard disk diffusion test. by Barry AL, Fernandes PB, Jorgensen JH, Thornsberry C, Hardy DJ, Jones RN.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266903
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with erythromycin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “erythromycin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for erythromycin (hyperlinks lead to article summaries): •
23S rRNA point mutation associated with erythromycin resistance in Treponema denticola. Author(s): Lee SY, Ning Y, Fenno JC. Source: Fems Microbiology Letters. 2002 January 22; 207(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886748&dopt=Abstract
•
A common clone of erythromycin-resistant Streptococcus pneumoniae in Greece and the UK. Author(s): Fotopoulou N, Tassios PT, Beste DV, Ioannidou S, Efstratiou A, Lawrence ER, Papaparaskevas J, George RC, Legakis NJ. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 924-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14616680&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
46
Erythromycin
•
A randomized, double-blind, multicenter, parallel group study to compare relative efficacies of the topical gels 3% erythromycin/5% benzoyl peroxide and 0.025% tretinoin/erythromycin 4% in the treatment of moderate acne vulgaris of the face. Author(s): Gupta AK, Lynde CW, Kunynetz RA, Amin S, Choi K, Goldstein E. Source: Journal of Cutaneous Medicine and Surgery. 2003 January-February; 7(1): 31-7. Epub 2002 October 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362264&dopt=Abstract
•
A randomized, parallel, vehicle-controlled comparison of two erythromycin/benzoyl peroxide preparations for acne vulgaris. Author(s): Thiboutot D, Jarratt M, Rich P, Rist T, Rodriguez D, Levy S. Source: Clinical Therapeutics. 2002 May; 24(5): 773-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075945&dopt=Abstract
•
A serotype V clone is predominant among erythromycin-resistant Streptococcus agalactiae isolates in a southwestern region of Germany. Author(s): von Both U, Ruess M, Mueller U, Fluegge K, Sander A, Berner R. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2166-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734270&dopt=Abstract
•
Activity of ketolide ABT-773 (cethromycin) against erythromycin-resistant Streptococcus pneumoniae: correlation with extended MLSK phenotypes. Author(s): Hamilton-Miller JM, Shah S. Source: The Journal of Antimicrobial Chemotherapy. 2002 December; 50(6): 907-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461012&dopt=Abstract
•
Addition of a 2-month low-dose course of levofloxacin to long-term erythromycin therapy in sinobronchial syndrome. Author(s): Fujimura M, Mizuguchi M, Nakatsumi Y, Mizuhashi K, Sasaki S, Yasui M; Kanazawa Asthma Research Group. Source: Respirology (Carlton, Vic.). 2002 December; 7(4): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421239&dopt=Abstract
•
An integron cassette encoding erythromycin esterase, ere(A), from Providencia stuartii. Author(s): Plante I, Centron D, Roy PH. Source: The Journal of Antimicrobial Chemotherapy. 2003 April; 51(4): 787-90. Epub 2003 March 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654734&dopt=Abstract
Studies
47
•
Analysis of erythromycin and oleandomycin residues in food by high-performance liquid chromatography with fluorometric detection. Author(s): Edder P, Coppex L, Cominoli A, Corvi C. Source: Food Additives and Contaminants. 2002 March; 19(3): 232-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834075&dopt=Abstract
•
Anti-inflammatory effects of erythromycin and tetracycline on Propionibacterium acnes induced production of chemotactic factors and reactive oxygen species by human neutrophils. Author(s): Jain A, Sangal L, Basal E, Kaushal GP, Agarwal SK. Source: Dermatology Online Journal [electronic Resource]. 2002 October; 8(2): 2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546757&dopt=Abstract
•
Bacterial resistance and therapeutic outcome following three months of topical acne therapy with 2% erythromycin gel versus its vehicle. Author(s): Mills O Jr, Thornsberry C, Cardin CW, Smiles KA, Leyden JJ. Source: Acta Dermato-Venereologica. 2002; 82(4): 260-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361129&dopt=Abstract
•
Beware of combining erythromycin with a statin. Author(s): Cenedella RJ. Source: J Am Osteopath Assoc. 2003 March; 103(3): 117. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665215&dopt=Abstract
•
Bioavailability and stability of erythromycin delayed release tablets. Author(s): Ogwal S, Xide TU. Source: Afr Health Sci. 2001 December; 1(2): 90-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789122&dopt=Abstract
•
Bordetella pertussis isolates with a heterogeneous phenotype for erythromycin resistance. Author(s): Wilson KE, Cassiday PK, Popovic T, Sanden GN. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2942-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149356&dopt=Abstract
•
Clinical and molecular epidemiology of erythromycin-resistant beta-hemolytic lancefield group G streptococci causing bacteremia. Author(s): Woo PC, To AP, Tse H, Lau SK, Yuen KY. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5188-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14605159&dopt=Abstract
48
Erythromycin
•
Clinical use of erythromycin in children with gastrointestinal dysmotility. Author(s): Aanpreung P, Vajaradul C. Source: J Med Assoc Thai. 2001 July; 84(7): 1021-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759961&dopt=Abstract
•
Clonal diversity among erythromycin-resistant beta-haemolytic Streptococcus isolates in La Rioja, Spain. Author(s): Portillo A, Gastanares MJ, Ruiz-Larrea F, Torres C. Source: The Journal of Antimicrobial Chemotherapy. 2003 September; 52(3): 485-8. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888595&dopt=Abstract
•
Clonal relationships among isolates of erythromycin-resistant Streptococcus pyogenes of different geographical origin. Author(s): Kataja J, Huovinen P, Efstratiou A, Perez-Trallero E, Seppala H; Macrolide resistance study group. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 August; 21(8): 589-95. Epub 2002 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226689&dopt=Abstract
•
Cluster of erythromycin- and ciprofloxacin-resistant Campylobacter jejuni subsp. jejuni from 1999 to 2001 in men who have sex with men, Quebec, Canada. Author(s): Gaudreau C, Michaud S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 131-6. Epub 2003 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830417&dopt=Abstract
•
Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children. Author(s): Kogan R, Martinez MA, Rubilar L, Paya E, Quevedo I, Puppo H, Girardi G, Castro-Rodriguez JA. Source: Pediatric Pulmonology. 2003 February; 35(2): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526069&dopt=Abstract
•
Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial. Author(s): Khan WA, Saha D, Rahman A, Salam MA, Bogaerts J, Bennish ML. Source: Lancet. 2002 November 30; 360(9347): 1722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480424&dopt=Abstract
Studies
49
•
Compound cardiac toxicity of oral erythromycin and verapamil. Author(s): Goldschmidt N, Azaz-Livshits T, Gotsman, Nir-Paz R, Ben-Yehuda A, Muszkat M. Source: The Annals of Pharmacotherapy. 2001 November; 35(11): 1396-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724091&dopt=Abstract
•
Conjugative transfer of the erm(A) gene from erythromycin-resistant Streptococcus pyogenes to macrolide-susceptible S. pyogenes, Enterococcus faecalis and Listeria innocua. Author(s): Giovanetti E, Magi G, Brenciani A, Spinaci C, Lupidi R, Facinelli B, Varaldo PE. Source: The Journal of Antimicrobial Chemotherapy. 2002 August; 50(2): 249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161406&dopt=Abstract
•
Correlation between erythromycin and azithromycin resistance in Streptococcus pneumoniae. Author(s): Wasas AD, Huebner RE, Hockman M, Klugman KP. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 April; 93(4): 283. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806721&dopt=Abstract
•
Cost-effectiveness of IV-to-oral switch therapy: azithromycin vs cefuroxime with or without erythromycin for the treatment of community-acquired pneumonia. Author(s): Paladino JA, Gudgel LD, Forrest A, Niederman MS. Source: Chest. 2002 October; 122(4): 1271-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377852&dopt=Abstract
•
Cytochrome P450 3A4 and P-glycoprotein mediate the interaction between an oral erythromycin breath test and rifampin. Author(s): Paine MF, Wagner DA, Hoffmaster KA, Watkins PB. Source: Clinical Pharmacology and Therapeutics. 2002 November; 72(5): 524-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426516&dopt=Abstract
•
Differences in the susceptibility of Streptococcus pyogenes to rokitamycin and erythromycin A revealed by morphostructural atomic force microscopy. Author(s): Braga PC, Ricci D. Source: The Journal of Antimicrobial Chemotherapy. 2002 October; 50(4): 457-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356788&dopt=Abstract
•
Direct inhibitory effect of erythromycin on human alimentary tract smooth muscle. Author(s): Nissan A, Freund HR, Hanani M. Source: American Journal of Surgery. 2002 April; 183(4): 413-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975929&dopt=Abstract
50
Erythromycin
•
Dissemination of clonally unrelated erythromycin- and glycopeptide-resistant Enterococcus faecium isolates in a tertiary Greek hospital. Author(s): Maniatis AN, Pournaras S, Kanellopoulou M, Kontos F, Dimitroulia E, Papafrangas E, Tsakris A. Source: Journal of Clinical Microbiology. 2001 December; 39(12): 4571-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724887&dopt=Abstract
•
Drug interaction between mosapride and erythromycin without electrocardiographic changes. Author(s): Katoh T, Saitoh H, Ohno N, Tateno M, Nakamura T, Dendo I, Kobayashi S, Nagasawa K. Source: Japanese Heart Journal. 2003 March; 44(2): 225-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718484&dopt=Abstract
•
Duodenogastric reflux after biliary surgery: scintigraphic quantification and improvement with erythromycin. Author(s): Fountos A, Chrysos E, Tsiaoussis J, Karkavitsas N, Zoras OJ, Katsamouris A, Xynos E. Source: Anz Journal of Surgery. 2003 June; 73(6): 400-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801337&dopt=Abstract
•
Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients. Author(s): Schmidt LE, Olsen AK, Stentoft K, Rasmussen A, Kirkegaard P, Dalhoff K. Source: Clinical Pharmacology and Therapeutics. 2001 November; 70(5): 446-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719731&dopt=Abstract
•
Effect of erythromycin and cisapride on emptying of the vagally denervated intrathoracic stomach. Author(s): Narasimhan R, Mittal BR, Gupta NM. Source: Trop Gastroenterol. 2002 July-September; 23(3): 122-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693153&dopt=Abstract
•
Effect of erythromycin on gastroduodenal contractile activity in developing neonates. Author(s): Steffen RM. Source: Clinical Pediatrics. 2002 July-August; 41(6): 448-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180432&dopt=Abstract
•
Effect of erythromycin on gastroduodenal contractile activity in developing neonates. Author(s): Jadcherla SR, Berseth CL. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 January; 34(1): 16-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753158&dopt=Abstract
Studies
51
•
Effect of low-dose oral erythromycin on gastric aspirates in ventilated neonates less than 32 weeks of gestation. Preliminary results. Author(s): Dellagrammaticas HD, Iacovidou N, Megaloyanni E, Papadimitriou M, Kapetanakis J. Source: Biology of the Neonate. 2002; 81(3): 213-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937729&dopt=Abstract
•
Effect of preoperative neomycin-erythromycin intestinal preparation on the incidence of infectious complications following colon surgery. 1973. Author(s): Nichols RL, Broido P, Condon RE, Gorbach SL, Nyhus LM. Source: Surgical Infections. 2000 Summer; 1(2): 133-41; Discussion 143, 145-6, 147-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594901&dopt=Abstract
•
Effect of preoperative oral use of erythromycin and nizatidine on gastric pH and volume. Author(s): Memis D, Turan A, Karamanlioglu B, Guler T, Yurdakoc A, Pamukcu Z, Turan N. Source: Anaesthesia and Intensive Care. 2002 August; 30(4): 428-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180579&dopt=Abstract
•
Effect of the CYP3A4 inhibitor erythromycin on the pharmacokinetics of lignocaine and its pharmacologically active metabolites in subjects with normal and impaired liver function. Author(s): Orlando R, Piccoli P, De Martin S, Padrini R, Palatini P. Source: British Journal of Clinical Pharmacology. 2003 January; 55(1): 86-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534644&dopt=Abstract
•
Effects of erythromycin on Pseudomonas aeruginosa adherence to collagen and morphology in vitro. Author(s): Tsang KW, Ng P, Ho PL, Chan S, Tipoe G, Leung R, Sun J, Ho JC, Ip MS, Lam WK. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 March; 21(3): 401-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661992&dopt=Abstract
•
Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: a prospective, randomized, single blind trial. Author(s): Lebel MH, Mehra S. Source: The Pediatric Infectious Disease Journal. 2001 December; 20(12): 1149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740322&dopt=Abstract
52
Erythromycin
•
emm Gene distribution among erythromycin-resistant and -susceptible Italian isolates of Streptococcus pyogenes. Author(s): Zampaloni C, Cappelletti P, Prenna M, Vitali LA, Ripa S. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1307-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624074&dopt=Abstract
•
Endothelial cell compatibility of azithromycin and erythromycin. Author(s): Vorbach H, Armbruster C, Robibaro B, Griesmacher A, El-Menyawi I, Daxecker H, Raab M, Muller MM. Source: The Journal of Antimicrobial Chemotherapy. 2002 February; 49(2): 407-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815590&dopt=Abstract
•
Enhanced anti-Shigella activity of erythromycin supplemented with sulfadiazine. Author(s): Honma Y, Sasakawa C, Tsuji T, Iwanaga M. Source: Fems Immunology and Medical Microbiology. 2001 December; 32(1): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750221&dopt=Abstract
•
Erythromycin accelerates gastric emptying in a dose-response manner in healthy subjects. Author(s): Boivin MA, Carey MC, Levy H. Source: Pharmacotherapy. 2003 January; 23(1): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523456&dopt=Abstract
•
Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro. Author(s): Sasaki M, Ito T, Kashima M, Fukui S, Izumiyama N, Watanabe A, Sano M, Fujiwara Y, Miura M. Source: Mediators of Inflammation. 2001 October; 10(5): 259-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759110&dopt=Abstract
•
Erythromycin and clindamycin resistance and telithromycin susceptibility in Streptococcus agalactiae. Author(s): Betriu C, Culebras E, Gomez M, Rodriguez-Avial I, Sanchez BA, Agreda MC, Picazo JJ. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 1112-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604549&dopt=Abstract
•
Erythromycin and early enteral nutrition in mechanically ventilated patients. Author(s): Reignier J, Bensaid S, Perrin-Gachadoat D, Burdin M, Boiteau R, Tenaillon A. Source: Critical Care Medicine. 2002 June; 30(6): 1237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072674&dopt=Abstract
Studies
53
•
Erythromycin and gastroduodenal contractile activity. Author(s): Orenstein SR. Source: Current Gastroenterology Reports. 2002 June; 4(3): 227-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010623&dopt=Abstract
•
Erythromycin as a gastrointestinal prokinetic agent. Author(s): Bradley C. Source: Intensive & Critical Care Nursing : the Official Journal of the British Association of Critical Care Nurses. 2001 April; 17(2): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817442&dopt=Abstract
•
Erythromycin as a prokinetic agent in preterm infants. Author(s): Costalos C, Gounaris A, Varhalama E, Kokori F, Alexiou N, Kolovou E. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 January; 34(1): 23-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753159&dopt=Abstract
•
Erythromycin as a prokinetic agent. Author(s): Kaul A. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 January; 34(1): 13-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753157&dopt=Abstract
•
Erythromycin fails to improve feeding outcome in feeding-intolerant preterm infants. Author(s): ElHennawy AA, Sparks JW, Armentrout D, Huseby V, Berseth CL. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 September; 37(3): 2816. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960650&dopt=Abstract
•
Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study. Author(s): Coffin B, Pocard M, Panis Y, Riche F, Laine MJ, Bitoun A, Lemann M, Bouhnik Y, Valleur P; Groupe des endoscopistes de garde a l'AP-HP. Source: Gastrointestinal Endoscopy. 2002 August; 56(2): 174-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145593&dopt=Abstract
•
Erythromycin in ELBW infants. Author(s): Shiima Y, Tsukahara H, Kobata R, Hayakawa K, Hiraoka M, Mayumi M. Source: The Journal of Pediatrics. 2002 August; 141(2): 297-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183739&dopt=Abstract
54
Erythromycin
•
Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells. Author(s): Suzuki T, Yamaya M, Sekizawa K, Hosoda M, Yamada N, Ishizuka S, Yoshino A, Yasuda H, Takahashi H, Nishimura H, Sasaki H. Source: American Journal of Respiratory and Critical Care Medicine. 2002 April 15; 165(8): 1113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956054&dopt=Abstract
•
Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Author(s): Frossard JL, Spahr L, Queneau PE, Giostra E, Burckhardt B, Ory G, De Saussure P, Armenian B, De Peyer R, Hadengue A. Source: Gastroenterology. 2002 July; 123(1): 17-23. Erratum In: Gastroenterology 2002 December; 123(6): 2162. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105828&dopt=Abstract
•
Erythromycin ototoxicity. Author(s): McGhan LJ, Merchant SN. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 July; 24(4): 701-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851569&dopt=Abstract
•
Erythromycin reduces delayed gastric emptying in critically ill trauma patients: a randomized, controlled trial. Author(s): Berne JD, Norwood SH, McAuley CE, Vallina VL, Villareal D, Weston J, McClarty J. Source: The Journal of Trauma. 2002 September; 53(3): 422-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352474&dopt=Abstract
•
Erythromycin resistance in Borrelia burgdorferi. Author(s): Terekhova D, Sartakova ML, Wormser GP, Schwartz I, Cabello FC. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3637-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384380&dopt=Abstract
•
Erythromycin resistance in italian isolates of Streptococcus pyogenes and correlations with pulsed-field gel electrophoresis analysis. Author(s): Zampaloni C, Vitali LA, Prenna M, Toscano MA, Tempera G, Ripa S. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Spring; 8(1): 39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002648&dopt=Abstract
Studies
55
•
Erythromycin susceptibility of viridans streptococci from the normal throat flora of patients treated with azithromycin or clarithromycin. Author(s): King A, Bathgate T, Phillips I. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 February; 8(2): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952721&dopt=Abstract
•
Erythromycin use during pregnancy in relation to pyloric stenosis. Author(s): Hussain N, Herson VC. Source: American Journal of Obstetrics and Gynecology. 2002 September; 187(3): 821-2; Author Reply 822. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237674&dopt=Abstract
•
Erythromycin use during pregnancy in relation to pyloric stenosis. Author(s): Louik C, Werler MM, Mitchell AA. Source: American Journal of Obstetrics and Gynecology. 2002 February; 186(2): 288-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854652&dopt=Abstract
•
Erythromycin-resistance of cutaneous bacterial flora in acne. Author(s): Dreno B, Reynaud A, Moyse D, Habert H, Richet H. Source: European Journal of Dermatology : Ejd. 2001 November-December; 11(6): 54953. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11701406&dopt=Abstract
•
Erythromycin-resistant group A streptococcal isolates recovered in Sofia, Bulgaria, from 1995 to 2001. Author(s): Detcheva A, Facklam RR, Beall B. Source: Journal of Clinical Microbiology. 2002 October; 40(10): 3831-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354892&dopt=Abstract
•
Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh. Author(s): Martin JM, Green M, Barbadora KA, Wald ER. Source: The New England Journal of Medicine. 2002 April 18; 346(16): 1200-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961148&dopt=Abstract
•
Erythromycin-resistant group A streptococci. Author(s): Shulman ST, Tanz R, Kabat W. Source: The New England Journal of Medicine. 2002 August 22; 347(8): 614-5; Author Reply 614-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195586&dopt=Abstract
56
Erythromycin
•
Erythromycin-resistant group A streptococci. Author(s): Linder JA, Stafford RS. Source: The New England Journal of Medicine. 2002 August 22; 347(8): 614-5; Author Reply 614-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192025&dopt=Abstract
•
Erythromycin-resistant pharyngeal isolates of Streptococcus pyogenes recovered in Italy. Author(s): Dicuonzo G, Fiscarelli E, Gherardi G, Lorino G, Battistoni F, Landi S, De Cesaris M, Petitti T, Beall B. Source: Antimicrobial Agents and Chemotherapy. 2002 December; 46(12): 3987-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435707&dopt=Abstract
•
Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. Author(s): Ng SC, Gomez JM, Rajadurai VS, Saw SM, Quak SH. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 5548. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581796&dopt=Abstract
•
Evaluation of the antibacterial potential of tetracycline or erythromycin mixed with calcium hydroxide as intracanal dressing against Enterococcus faecalis in vivo. Author(s): Molander A, Dahlen G. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 December; 96(6): 744-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676767&dopt=Abstract
•
Evolution of penicillin and erythromycin co-resistance in Streptococcus pneumoniae in Spain. Author(s): Garcia-Rey C, Bouza E, Aguilar L, Garcia-de-Lomas J, Baquero F; Spanish Surveillance Group for Respiratory Pathogens. Source: International Journal of Antimicrobial Agents. 2003 November; 22(5): 541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602376&dopt=Abstract
•
Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants. Author(s): Baier RJ, Loggins J, Kruger TE. Source: Bmc Pediatrics [electronic Resource]. 2003 September 04; 3(1): 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956892&dopt=Abstract
Studies
57
•
Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Author(s): Lonks JR, Garau J, Gomez L, Xercavins M, Ochoa de Echaguen A, Gareen IF, Reiss PT, Medeiros AA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 September 1; 35(5): 556-64. Epub 2002 August 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173129&dopt=Abstract
•
Gastropyloric motor activity and the effects of erythromycin given orally after esophagectomy. Author(s): Nakabayashi T, Mochiki E, Garcia M, Haga N, Kato H, Suzuki T, Asao T, Kuwano H. Source: American Journal of Surgery. 2002 March; 183(3): 317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943134&dopt=Abstract
•
Genotypic identification of erythromycin-resistant campylobacter isolates as helicobacter species and analysis of resistance mechanism. Author(s): Kuijper EJ, Stevens S, Imamura T, De Wever B, Claas EC. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3732-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904383&dopt=Abstract
•
Hazards of widespread use of erythromycin for preterm prelabour rupture of membranes. Author(s): Tan S, Holliman R, Russell AR. Source: Lancet. 2003 February 1; 361(9355): 437. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573418&dopt=Abstract
•
High frequency of erythromycin A resistance and distribution of mefE and ermB genes in clinical isolates of Streptococcus pneumoniae in Japan. Author(s): Okamoto H, Tateda K, Ishii Y, Matsumoto T, Kobayashi T, Miyazaki S, Yamaguchi K. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 March; 8(1): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957116&dopt=Abstract
•
High prevalence of erythromycin resistance of Streptococcus pyogenes in Greek children. Author(s): Syrogiannopoulos GA, Grivea IN, Fitoussi F, Doit C, Katopodis GD, Bingen E, Beratis NG. Source: The Pediatric Infectious Disease Journal. 2001 September; 20(9): 863-8. Erratum In: Pediatr Infect Dis J 2001 December; 20(12): 1131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734765&dopt=Abstract
58
Erythromycin
•
Hyperglycemia attenuates erythromycin-induced acceleration of liquid-phase gastric emptying of hypertonic liquids in healthy subjects. Author(s): Petrakis IE, Kogerakis N, Prokopakis G, Zacharioudakis G, Antonakakis S, Vrachassotakis N, Chalkiadakis G. Source: Digestive Diseases and Sciences. 2002 January; 47(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837735&dopt=Abstract
•
Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects. Author(s): Petrakis IE, Kogerakis N, Vrachassotakis N, Stiakakis I, Zacharioudakis G, Chalkiadakis G. Source: Abdominal Imaging. 2002 May-June; 27(3): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173362&dopt=Abstract
•
Identification of a mutation associated with erythromycin resistance in Bordetella pertussis: implications for surveillance of antimicrobial resistance. Author(s): Bartkus JM, Juni BA, Ehresmann K, Miller CA, Sanden GN, Cassiday PK, Saubolle M, Lee B, Long J, Harrison AR Jr, Besser JM. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624047&dopt=Abstract
•
Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae. Author(s): Garcia-Rey C, Aguilar L, Baquero F, Casal J, Dal-Re R. Source: Journal of Clinical Microbiology. 2002 January; 40(1): 159-64. Erratum In: J Clin Microbiol 2002 May; 40(5): 1885. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773111&dopt=Abstract
•
In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children. Author(s): Johnson CN, Benjamin WH Jr, Gray BM, Crain MC, Edwards KM, Waites KB. Source: International Journal of Antimicrobial Agents. 2001 December; 18(6): 531-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738340&dopt=Abstract
•
In vitro activity of fluoroquinolones against erythromycin-susceptible and -resistant Bordetella pertussis. Author(s): Bourgeois N, Ghnassia JC, Doucet-Populaire F. Source: The Journal of Antimicrobial Chemotherapy. 2003 March; 51(3): 742-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615884&dopt=Abstract
Studies
59
•
Increased prevalence of erythromycin resistance in streptococci: substantial upsurge in erythromycin-resistant M phenotype in Streptococcus pyogenes (1979-1998) but not in Streptococcus pneumoniae (1985-1999) in Taiwan. Author(s): Hsueh PR, Teng LJ, Lee LN, Yang PC, Ho SW, Lue HC, Luh KT. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Spring; 8(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002646&dopt=Abstract
•
Inhibition of human neutrophil elastase by erythromycin and flurythromycin, two macrolide antibiotics. Author(s): Gorrini M, Lupi A, Viglio S, Pamparana F, Cetta G, Iadarola P, Powers JC, Luisetti M. Source: American Journal of Respiratory Cell and Molecular Biology. 2001 October; 25(4): 492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694455&dopt=Abstract
•
Intravenous erythromycin facilitates bedside placement of postpyloric feeding tubes in critically ill adults: a double-blind, randomized, placebo-controlled study. Author(s): Griffith DP, McNally AT, Battey CH, Forte SS, Cacciatore AM, Szeszycki EE, Bergman GF, Furr CE, Murphy FB, Galloway JR, Ziegler TR. Source: Critical Care Medicine. 2003 January; 31(1): 39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544991&dopt=Abstract
•
Intravenous low-dose erythromycin administration for infants with feeding intolerance. Author(s): Nogami K, Nishikubo T, Minowa H, Uchida Y, Kamitsuji H, Takahashi Y. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 December; 43(6): 605-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737737&dopt=Abstract
•
Investigation of Staphylococcus aureus isolates identified as erythromycin intermediate by the Vitek-1 System: comparison with results obtained with the Vitek2 and Phoenix systems. Author(s): Tang P, Low DE, Atkinson S, Pike K, Ashi-Sulaiman A, Simor A, Richardson S, Willey BM. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4823-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532232&dopt=Abstract
•
Is penicillin and/or erythromycin resistance present in clinical isolates of group B streptococcus in our community? Author(s): Stylianopoulos A, Kelly N, Garland S. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 November; 42(5): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495105&dopt=Abstract
60
Erythromycin
•
Lack of clinically relevant interaction between desloratadine and erythromycin. Author(s): Banfield C, Hunt T, Reyderman L, Statkevich P, Padhi D, Affrime M. Source: Clinical Pharmacokinetics. 2002; 41 Suppl 1: 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169044&dopt=Abstract
•
Linear IgA disease: successful treatment with erythromycin. Author(s): Cooper SM, Powell J, Wojnarowska F. Source: Clinical and Experimental Dermatology. 2002 November; 27(8): 677-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472545&dopt=Abstract
•
Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy. Author(s): Ohwada S, Satoh Y, Kawate S, Yamada T, Kawamura O, Koyama T, Yoshimura S, Tomizawa N, Ogawa T, Morishita Y. Source: Annals of Surgery. 2001 November; 234(5): 668-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685031&dopt=Abstract
•
Macrolide-resistant pneumococcal endocarditis and epidural abscess that develop during erythromycin therapy. Author(s): Butler JC, Lennox JL, McDougal LK, Sutcliffe JA, Tait-Kamradt A, Tenover FC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 January 15; 36(2): E19-25. Epub 2003 Jan 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522763&dopt=Abstract
•
Molecular characterization of erythromycin-resistant clinical isolates of the four major antimicrobial-resistant Spanish clones of Streptococcus pneumoniae (Spain23F-1, Spain6B-2, Spain9V-3, and Spain14-5). Author(s): Marimon JM, Iglesias L, Vicente D, Perez-Trallero E. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Summer; 9(2): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820797&dopt=Abstract
•
Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae isolates from blood and noninvasive sites. Author(s): Amezaga MR, Carter PE, Cash P, McKenzie H. Source: Journal of Clinical Microbiology. 2002 September; 40(9): 3313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202572&dopt=Abstract
•
No clinically significant effect of erythromycin or azithromycin on the pharmacokinetics of voriconazole in healthy male volunteers. Author(s): Purkins L, Wood N, Ghahramani P, Kleinermans D, Layton G, Nichols D. Source: British Journal of Clinical Pharmacology. 2003 December; 56 Suppl 1: 30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14616411&dopt=Abstract
Studies
61
•
Nuclear inheritance of erythromycin resistance in human cells: new class of mitochondrial protein synthesis mutants. Author(s): Doersen CJ, Stanbridge EJ. Source: Molecular and Cellular Biology. 1982 June; 2(6): 694-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14582164&dopt=Abstract
•
Octreotide enhances the accelerating effect of erythromycin on gastric emptying in healthy subjects. Author(s): Athanasakis E, Chrysos E, Zoras OJ, Tsiaoussis J, Karkavitsas N, Xynos E. Source: Alimentary Pharmacology & Therapeutics. 2002 August; 16(8): 1563-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182757&dopt=Abstract
•
One-year low-dose erythromycin treatment of persistent chronic sinusitis after sinus surgery: clinical outcome and effects on mucociliary parameters and nasal nitric oxide. Author(s): Cervin A, Kalm O, Sandkull P, Lindberg S. Source: Otolaryngology and Head and Neck Surgery. 2002 May; 126(5): 481-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075221&dopt=Abstract
•
Open-Label, parallel-group, multicenter, randomized study of cefprozil versus erythromycin in children with group A streptococcal pharyngitis/tonsillitis. Author(s): Brook I, Aronovitz GH, Pichichero ME. Source: Clinical Therapeutics. 2001 November; 23(11): 1889-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768840&dopt=Abstract
•
Oral erythromycin and symptomatic relief of gastroparesis: a systematic review. Author(s): Maganti K, Onyemere K, Jones MP. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 259-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591038&dopt=Abstract
•
Oral erythromycin for treatment of feeding intolerance in preterm infants: a preliminary report. Author(s): Sekteera W, Nuntnarumit P, Supapannachart S. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549792&dopt=Abstract
•
Oral erythromycin prophylaxis vs watchful waiting in caring for newborns exposed to Chlamydia trachomatis. Author(s): Rosenman MB, Mahon BE, Downs SM, Kleiman MB. Source: Archives of Pediatrics & Adolescent Medicine. 2003 June; 157(6): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796237&dopt=Abstract
62
Erythromycin
•
Outbreak of scarlet fever caused by an erythromycin-resistant Streptococcus pyogenes emm22 genotype strain in a day-care center. Author(s): Espinosa de los Monteros LE, Bustos IM, Flores LV, Avila-Figueroa C. Source: The Pediatric Infectious Disease Journal. 2001 August; 20(8): 807-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734748&dopt=Abstract
•
Penicillin-susceptible and erythromycin-resistant Streptococcus pneumoniae in children with acute mastoiditis. Author(s): del Castillo F, Ledesma F, Garcia-Perea A. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2001 November; 20(11): 824-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783702&dopt=Abstract
•
Pharmacoepidemiological analysis of provincial differences between consumption of macrolides and rates of erythromycin resistance among Streptococcus pyogenes isolates in Spain. Author(s): Garcia-Rey C, Aguilar L, Baquero F, Casal J, Martin JE. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2959-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149359&dopt=Abstract
•
Pharmacokinetic-pharmacodynamic modeling of the inhibitory effect of erythromycin on tumour necrosis factor-alpha and interleukin-6 production. Author(s): Guchelaar HJ, Schultz MJ, van der Poll T, Koopmans RP. Source: Fundamental & Clinical Pharmacology. 2001 December; 15(6): 419-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860530&dopt=Abstract
•
Phenotypic and molecular characterization of tetracycline- and erythromycin-resistant strains of Streptococcus pneumoniae. Author(s): Montanari MP, Cochetti I, Mingoia M, Varaldo PE. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2236-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821474&dopt=Abstract
•
Predominance of serotype V and frequency of erythromycin resistance in Streptococcus agalactiae in Ohio. Author(s): Croak A, Abate G, Goodrum K, Modrzakowski M. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1148-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748459&dopt=Abstract
Studies
63
•
Predominance of two M-types among erythromycin-resistant group A Streptococci from Greek children. Author(s): Zachariadou L, Papaparaskevas J, Paraskakis I, Efstratiou A, Pangalis A, Legakis NJ, Tassios PT. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 April; 9(4): 310-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667242&dopt=Abstract
•
Pre-operative oral erythromycin reduces residual gastric volume and acidity. Author(s): Asai T, Murao K, Shingu K. Source: British Journal of Anaesthesia. 2000 December; 85(6): 861-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732520&dopt=Abstract
•
Prevalence of erm(A) and mef(B) erythromycin resistance determinants in isolates of Streptococcus pneumoniae from New Zealand. Author(s): Bean DC, Klena JD. Source: The Journal of Antimicrobial Chemotherapy. 2002 October; 50(4): 597-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356808&dopt=Abstract
•
QT prolongation and torsades de pointes associated with concurrent use of cisapride and erythromycin. Author(s): Kyrmizakis DE, Chimona TS, Kanoupakis EM, Papadakis CE, Velegrakis GA, Helidonis ES. Source: American Journal of Otolaryngology. 2002 September-October; 23(5): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239699&dopt=Abstract
•
Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women. Author(s): Andrews WW, Sibai BM, Thom EA, Dudley D, Ernest JM, McNellis D, Leveno KJ, Wapner R, Moawad A, O'Sullivan MJ, Caritis SN, Iams JD, Langer O, Miodovnik M, Dombrowski M; National Institute of Child Health & Human Development Maternal-Fetal Medicine Units Network. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 1): 847-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738139&dopt=Abstract
•
Randomized, open-label, parallel-group, multicenter study of the efficacy and tolerability of IV gatifloxacin with the option for oral stepdown gatifloxacin versus IV ceftriaxone (with or without erythromycin or clarithromycin) with the option for oral stepdown clarithromycin for treatment of patients with mild to moderate community-acquired pneumonia requiring hospitalization. Author(s): Correa JC, Badaro R, Bumroongkit C, Mera JR, Dolmann AL, Juarez Martinez LG, Mayrinck LR, Tamez R, Yang JY. Source: Clinical Therapeutics. 2003 May; 25(5): 1453-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867221&dopt=Abstract
64
Erythromycin
•
Relationship between postoperative erythromycin breath test and early morbidity in liver transplant recipients. Author(s): Schmidt LE, Rasmussen A, Kirkegaard P, Dalhoff K. Source: Transplantation. 2003 July 27; 76(2): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883193&dopt=Abstract
•
Risk of torsades de pointes from oral erythromycin with concomitant carbimazole (methimazole) administration. Author(s): Koh TW. Source: Pacing and Clinical Electrophysiology : Pace. 2001 October; 24(10): 1575-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707056&dopt=Abstract
•
Role of erythromycin for treatment of incipient chronic lung disease in preterm infants colonised with Ureaplasma urealyticum. Author(s): Buhrer C, Hoehn T, Hentschel J. Source: Drugs. 2001; 61(13): 1893-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708762&dopt=Abstract
•
Severe erythema nodosum due to Behcet's disease responsive to erythromycin. Author(s): Kaya TI, Tursen U, Baz K, Ikizoglu G, Dusmez D. Source: The Journal of Dermatological Treatment. 2003 June; 14(2): 124-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775321&dopt=Abstract
•
Significant increase in the prevalence of erythromycin-resistant, clindamycin- and miocamycin-susceptible (M phenotype) Streptococcus pyogenes in Spain. Author(s): Alos JI, Aracil B, Oteo J, Gomez-Garces JL; Spanish Group for the Study of Infection in the Primary Health Care Setting (IAP-SEIMC). Source: The Journal of Antimicrobial Chemotherapy. 2003 February; 51(2): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562699&dopt=Abstract
•
Spread of erythromycin-, tetracycline-, and aminoglycoside-resistant genes in methicillin-resistant Staphylococcus aureus clinical isolates in a Kumamoto Hospital. Author(s): Sekiguchi J, Fujino T, Saruta K, Kawano F, Takami J, Miyazaki H, Kuratsuji T, Yoshikura H, Kirikae T. Source: Japanese Journal of Infectious Diseases. 2003 June; 56(3): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944686&dopt=Abstract
•
Survey of emm gene sequences from pharyngeal Streptococcus pyogenes isolates collected in Spain and their relationship with erythromycin susceptibility. Author(s): Alberti S, Garcia-Rey C, Dominguez MA, Aguilar L, Cercenado E, Gobernado M, Garcia-Perea A; Spanish Surviellance Group for Respiratory Pathogens. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2385-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791853&dopt=Abstract
Studies
65
•
Susceptibilities of Campylobacter jejuni isolates from Germany to ciprofloxacin, moxifloxacin, erythromycin, clindamycin, and tetracycline. Author(s): Wagner J, Jabbusch M, Eisenblatter M, Hahn H, Wendt C, Ignatius R. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2358-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821499&dopt=Abstract
•
Susceptibility to antimicrobials and mechanisms of erythromycin resistance in clinical isolates of Streptococcus agalactiae from Rio de Janeiro, Brazil. Author(s): d'Oliveira RE, Barros RR, Mendonca CR, Teixeira LM, Castro AC. Source: Journal of Medical Microbiology. 2003 November; 52(Pt 11): 1029-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532350&dopt=Abstract
•
The association of erythromycin and infantile hypertrophic pyloric stenosis: causal or coincidental? Author(s): Hauben M, Amsden GW. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(13): 929-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381214&dopt=Abstract
•
The effect of benzoyl peroxide and benzoyl peroxide/erythromycin combination on the antioxidative defence system in papulopustular acne. Author(s): Basak PY, Gultekin F, Kilinc I, Delibas N. Source: European Journal of Dermatology : Ejd. 2002 January-February; 12(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809596&dopt=Abstract
•
The effect of erythromycin and clarithromycin on the pharmacokinetics of intravenous digoxin in healthy volunteers. Author(s): Tsutsumi K, Kotegawa T, Kuranari M, Otani Y, Morimoto T, Matsuki S, Nakano S. Source: Journal of Clinical Pharmacology. 2002 October; 42(10): 1159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362931&dopt=Abstract
•
The effect of erythromycin on bile excretion and proximal small bowel motility following divided gastric bypass surgery: a prospective randomized placebocontrolled trial. Author(s): Wilkinson NW, Gustafson RJ, Frizzi JD. Source: Obesity Surgery : the Official Journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. 2002 December; 12(6): 765-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568180&dopt=Abstract
66
Erythromycin
•
The effect of erythromycin on mucociliary transportability and rheology of cystic fibrosis and bronchiectasis sputum. Author(s): Shibuya Y, Wills PJ, Cole PJ. Source: Respiration; International Review of Thoracic Diseases. 2001; 68(6): 615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786718&dopt=Abstract
•
The effect of erythromycin on the pharmacokinetics of rosuvastatin. Author(s): Cooper KJ, Martin PD, Dane AL, Warwick MJ, Raza A, Schneck DW. Source: European Journal of Clinical Pharmacology. 2003 May; 59(1): 51-6. Epub 2003 April 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682802&dopt=Abstract
•
The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers. Author(s): Muirhead GJ, Faulkner S, Harness JA, Taubel J. Source: British Journal of Clinical Pharmacology. 2002; 53 Suppl 1: 37S-43S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11879258&dopt=Abstract
•
Time-resolved three-dimensional MR imaging of gastric emptying modified by IV administration of erythromycin. Author(s): Lauenstein TC, Vogt FM, Herborn CU, DeGreiff A, Debatin JF, Holtmann G. Source: Ajr. American Journal of Roentgenology. 2003 May; 180(5): 1305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704042&dopt=Abstract
•
Trends in Streptococcus pyogenes resistance to erythromycin in Slovakia: is there a correlation with consumption? Author(s): Krcmery V, Foltan V, Langsadl L, Liskov A, Babela R. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(5): 400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069033&dopt=Abstract
•
UK guidelines for use of erythromycin chemoprophylaxis in persons exposed to pertussis. Author(s): Dodhia H, Crowcroft NS, Bramley JC, Miller E. Source: Journal of Public Health Medicine. 2002 September; 24(3): 200-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831090&dopt=Abstract
•
Use of erythromycin for the treatment of severe chronic constipation in children. Author(s): Bellomo-Brandao MA, Collares EF, da-Costa-Pinto EA. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2003 October; 36(10): 1391-6. Epub 2003 September 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502372&dopt=Abstract
Studies
67
•
Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Author(s): Cooper WO, Griffin MR, Arbogast P, Hickson GB, Gautam S, Ray WA. Source: Archives of Pediatrics & Adolescent Medicine. 2002 July; 156(7): 647-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090829&dopt=Abstract
•
Why not to use erythromycin in GI motility. Author(s): Guerin JM, Leibinger F. Source: Chest. 2002 January; 121(1): 301-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796472&dopt=Abstract
69
CHAPTER 2. NUTRITION AND ERYTHROMYCIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and erythromycin.
Finding Nutrition Studies on Erythromycin 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 “erythromycin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
70
Erythromycin
The following information is typical of that found when using the “Full IBIDS Database” to search for “erythromycin” (or a synonym): •
Acetaminophen as a marker of gastric emptying in ponies. Author(s): Department of Large Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee 37901-1071 (USA) Source: Doherty, T.J. Andrews, F.M. Provenza, M.K. Frazier, D.L. Equine-VeterinaryJournal (United Kingdom). (1998). volume 30(4) page 349-351.
Additional physician-oriented references include: •
A double-blind controlled evaluation of the sebosuppressive activity of topical erythromycin-zinc complex. Author(s): Department of Dermatopathology, University of Liege, Belgium. Source: Pierard Franchimont, C Goffin, V Visser, J N Jacoby, H Pierard, G E Eur-J-ClinPharmacol. 1995; 49(1-2): 57-60 0031-6970
•
Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome. Author(s): Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan. Source: Ishiura, Y Fujimura, M Saito, M Shibata, K Nomura, M Nakatsumi, Y Matsuda, T Respir-Med. 1995 November; 89(10): 677-84 0954-6111
•
An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs. Author(s): Biology Research Laboratories, Takeda Chemical Industries, Osaka, Japan. Source: Inatomi, N Satoh, H Maki, Y Hashimoto, N Itoh, Z Omura, S J-Pharmacol-ExpTher. 1989 November; 251(2): 707-12 0022-3565
•
An in-vitro comparison of the intraphagocytic bioactivity of erythromycin and roxithromycin. Author(s): Department of Medical Microbiology, University of Pretoria, Republic of South Africa. Source: Anderson, R Van Rensburg, C E Joone, G Lukey, P T J-Antimicrob-Chemother. 1987 November; 20 Suppl B57-68 0305-7453
•
Antilymphocytic activity of erythromycin distinct from that of FK506 or cyclosporin A. Author(s): Department of Immunology, National Institute of Health, Tokyo, Japan. Source: Keicho, N Kudoh, S Yotsumoto, H Akagawa, K S J-Antibiot-(Tokyo). 1993 September; 46(9): 1406-13 0021-8820
•
Cloning of erythromycin-resistance determinants and replication origins from indigenous plasmids of Lactobacillus reuteri for potential use in construction of cloning vectors. Author(s): Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan, ROC. Source: Lin, C F Chung, T C Plasmid. 1999 July; 42(1): 31-41 0147-619X
•
Cluster of an erythromycin-resistant variant of the Spanish multiply resistant 23F clone of Streptococcus pneumoniae in South Africa. Author(s): Department of Medical Microbiology, University of the Witwatersrand, Johannesburg, South Africa.
Nutrition
71
Source: Klugman, K P Coffey, T J Smith, A Wasas, A Meyers, M Spratt, B G Eur-J-ClinMicrobiol-Infect-Dis. 1994 February; 13(2): 171-4 0934-9723 •
Densitometric thin layer chromatographic analysis of tretinoin and erythromycin in lotions for topical use in acne treatment. Author(s): Pharmaceutical Institute, Vrije Universiteit Brussel, Brussels, Belgium. Source: Gabriels, M Brisaert, M Plaizier Vercammen, J Eur-J-Pharm-Biopharm. 1999 July; 48(1): 53-8 0939-6411
•
Description of the erythromycin-producing bacterium Arthrobacter sp. strain NRRL B-3381 as Aeromicrobium erythreum gen. nov., sp. nov. Author(s): Department of Microbiology, North Carolina State University, Raleigh 27695. Source: Miller, E S Woese, C R Brenner, S Int-J-Syst-Bacteriol. 1991 July; 41(3): 363-8 0020-7713
•
Detection of erythromycin resistant methylase gene by the polymerase chain reaction. Author(s): Division of Microbiology, National Center for Toxicological Research, Jefferson, AR 72079, USA. Source: Nawaz, M S Khan, A A Cerniglia, C E Mol-Cell-Probes. 1997 October; 11(5): 31722 0890-8508
•
Effect of erythromycin on ciliary motility in rabbit airway epithelium in vitro. Author(s): First Department of Medicine, Tokyo Women's Medical College, Japan. Source: Tamaoki, J Chiyotani, A Sakai, N Takeyama, K Takizawa, T J-AntimicrobChemother. 1992 February; 29(2): 173-8 0305-7453
•
Efficacy and tolerability of combined topical treatment of acne vulgaris with tretinoin and erythromycin in general practice. Author(s): Dermatology Clinic and Polyclinic, Ludwig-Maximilian University, Munich, Federal Republic of Germany. Source: Korting, H C Braun Falco, O Drugs-Exp-Clin-Res. 1989; 15(9): 447-51 0378-6501
•
EM-523, an erythromycin derivative, and motilin show similar contractile activity in isolated rabbit intestine. Author(s): Research Department, Shimizu Pharmaceutical Co., Ltd., Shizuoka, Japan. Source: Satoh, T Inatomi, N Satoh, H Marui, S Itoh, Z Omura, S J-Pharmacol-Exp-Ther. 1990 September; 254(3): 940-4 0022-3565
•
Ergotism precipitated by erythromycin: a rare case of vasospasm. Author(s): Departments of Cardiovascular Surgery and Internal Medicine, Hotel-Dieu de France, Beirut, Lebanon. Source: Karam, B Farah, E Ashoush, R Jebara, V Ghayad, E Eur-J-Vasc-Endovasc-Surg. 2000 January; 19(1): 96-8 1078-5884
•
Erythromycin base-induced rash and liver function disturbances. Author(s): Department of Internal Medicine D, Sackler Faculty of Medicine, Tel Aviv University, Petah Tiqva, Israel. Source: Shirin, H Schapiro, J M Arber, N Pinkhas, J Sidi, Y Salomon, F AnnPharmacother. 1992 December; 26(12): 1522-3 1060-0280
•
Erythromycin inhibits ATP-induced intracellular calcium responses in bovine tracheal epithelial cells. Author(s): First Department of Medicine and Second Department of Physiology, Tokyo Women's Medical College, Tokyo, Japan. Source: Kondo, M Kanoh, S Tamaoki, J Shirakawa, H Miyazaki, S Nagai, A Am-J-RespirCell-Mol-Biol. 1998 November; 19(5): 799-804 1044-1549
72
Erythromycin
•
Erythromycin: pharmacokinetics, bioavailability, nonantimicrobial activity, and possible mechanisms associated with adverse reactions. Source: Lakritz, J. Wilson, W.D. Proc-annu-conv-Am-Assoc-Equine-Pract. Lexington, Ky. : American Association of Equine Practitioner. 1997. volume 43 page 83-86. 00657182
•
Erythromycin-associated ergotamine intoxication: arteriographic and electrophysiologic analysis of a rare cause of severe ischemia of the lower extremities and associated ischemic neuropathy. Author(s): Department of Surgery, St. Sacrement Hospital, Laval University, Quebec, Canada. Source: Ghali, R De Lean, J Douville, Y Noel, H P Labbe, R Ann-Vasc-Surg. 1993 May; 7(3): 291-6 0890-5096
•
Evaluation of 99mTc-erythromycin and 99mTc-streptomycin sulphate for the visualization of inflammatory lesions. Author(s): Department of Nuclear Medicine, Hacettepe University Medical Faculty, Ankara, Turkey. Source: Ercan, M T Aras, T Unsal, I S Int-J-Rad-Appl-Instrum-B. 1992 October; 19(7): 803-6 0883-2897
•
Gastric but not duodenal motor effects of oral erythromycin are dose related. Author(s): Equipe des flux digestifs, Station de Recherches porcines, INRA, Saint Gilles, France. Source: Mathis, C Malbert, C H Neurogastroenterol-Motil. 1995 March; 7(1): 47-54 13501925
•
Identification and cloning of a plasmid-encoded erythromycin resistance determinant from Lactobacillus reuteri. Author(s): Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala. Source: Axelsson, L T Ahrne, S E Andersson, M C Stahl, S R Plasmid. 1988 September; 20(2): 171-4 0147-619X
•
In vitro development of resistance to enrofloxacin, erythromycin, tylosin, tiamulin and oxytetracycline in Mycoplasma gallisepticum, Mycoplasma iowae and Mycoplasma synoviae. Author(s): Agence Francaise de Securite Sanitaire des Aliments, Laboratoire d'Etudes et de Recherches Avicoles et Porcines, Unite de Mycoplasmologie-Bacteriologie, BP 53, 22440, Ploufragan, France.
[email protected] Source: Gautier Bouchardon, A V Reinhardt, A K Kobisch, M Kempf, I Vet-Microbiol. 2002 August 2; 88(1): 47-58 0378-1135
•
Interaction of artemisinin and tetracycline or erythromycin against Plasmodium falciparum in vitro. Author(s): Department of Pharmacology, China Academy of Traditional Chinese Medicine, Beijing, China. Source: Ye, Z Van Dyke, K Parasite. 1994 September; 1(3): 211-8 1252-607X
•
Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with Streptococcus pneumoniae. Author(s): Laboratory of Experimental Internal Medicine, Department of Intensive Care, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
[email protected]
Nutrition
73
Source: Schultz, M J Speelman, P Hack, C E Buurman, W A van Deventer, S J van Der Poll, T J-Antimicrob-Chemother. 2000 August; 46(2): 235-40 0305-7453 •
In-vitro and in-vivo efficacy of zinc acetate against propionibacteria alone and in combination with erythromycin. Author(s): Dept. of Dermatology, Klinikum Karlsruhe, Germany.
[email protected] Source: Fluhr, J W Bosch, B Gloor, M Hoffler, U Zentralbl-Bakteriol. 1999 October; 289(4): 445-56 0934-8840
•
Isolation and characterization of a plasmid from Lactobacillus fermentum conferring erythromycin resistance. Author(s): Unite d'Ecologie et de Physiologie du Systeme Digestif, Institut National de la Recherche Agronomique, Jouy-en-Josas, France. Source: Fons, M Hege, T Ladire, M Raibaud, P Ducluzeau, R Maguin, E Plasmid. 1997; 37(3): 199-203 0147-619X
•
Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythraea. Author(s): Fermalogic, Inc., Chicago, IL 60612, USA. Source: Hessler, P E Larsen, P E Constantinou, A I Schram, K H Weber, J M ApplMicrobiol-Biotechnol. 1997 April; 47(4): 398-404 0175-7598
•
Molecular characterization of a plasmid-borne (pGT633) erythromycin resistance determinant (ermGT) from Lactobacillus reuteri 100-63. Author(s): Department of Microbiology, University of Otago, Dunedin, New Zealand. Source: Tannock, G W Luchansky, J B Miller, L Connell, H Thode Andersen, S Mercer, A A Klaenhammer, T R Plasmid. 1994 January; 31(1): 60-71 0147-619X
•
Serious erythromycin interactions caused by inhibition of drug metabolism in the liver. Author(s): Department of Oral-Craniofacial Biological Sciences, Dental School, University of Maryland at Baltimore, USA. Source: Wynn, R L Gen-Dent. 1996 Nov-December; 44(6): 486-8, 490 0363-6771
•
Synthesis of erythromycin by resting cells of Streptomyces erythreus. Source: Mandal, S K Bandyopadhyay, A Das, A K Indian-J-Exp-Biol. 1988 January; 26(1): 25-7 0019-5189
•
The effects of grapefruit juice on the pharmacokinetics of erythromycin. Author(s): Department of Pharmacy, Hirosaki University Hospital, Japan. Source: Kanazawa, S Ohkubo, T Sugawara, K Eur-J-Clin-Pharmacol. 2001 Jan-February; 56(11): 799-803 0031-6970
•
The interaction of erythromycin with theophylline. Source: Paulsen, O Hoglund, P Nilsson, L G Bengtsson, H I Eur-J-Clin-Pharmacol. 1987; 32(5): 493-8 0031-6970
•
The theophylline-erythromycin interaction. Author(s): Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada. Source: Rieder, M J Spino, M J-Asthma. 1988; 25(4): 195-204 0277-0903
•
Vinblastine and erythromycin: an unrecognized serious drug interaction. Author(s): Division of Nephrology, Sunnybrook Health Science Centre, University of Toronto, Canada. Source: Tobe, S W Siu, L L Jamal, S A Skorecki, K L Murphy, G F Warner, E CancerChemother-Pharmacol. 1995; 35(3): 188-90 0344-5704
74
•
Erythromycin
Vitamin A metabolism is altered in brown Norway and long-Evans rats infused with naftidrofuryl or erythromycin intravenously. Author(s): Department of Human Nutrition and Food Science, Dusternbrooker Weg 17, Christian-Albrechts-University, D-24116 Kiel, Germany.
[email protected] Source: Schindler, R Fielenbach, T Rave, G Blomer, A Kellersmann, R Int-J-Vitam-NutrRes. 2002 July; 72(4): 210-20 0300-9831
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
•
The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
•
The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
•
The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
•
Healthnotes: http://www.healthnotes.com/
•
Open Directory Project: http://dmoz.org/Health/Nutrition/
•
Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
•
WebMD®Health: http://my.webmd.com/nutrition
Nutrition
•
75
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to erythromycin; 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: •
Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin K Source: Healthnotes, Inc.; www.healthnotes.com
•
Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html
77
CHAPTER 3. ERYTHROMYCIN
ALTERNATIVE
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to erythromycin. 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 erythromycin 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 “erythromycin” (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 erythromycin: •
A combination effect of epigallocatechin gallate, a major compound of green tea catechins, with antibiotics on Helicobacter pylori growth in vitro. Author(s): Yanagawa Y, Yamamoto Y, Hara Y, Shimamura T. Source: Current Microbiology. 2003 September; 47(3): 244-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570277&dopt=Abstract
•
A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Author(s): Ogg MS, Williams JM, Tarbit M, Goldfarb PS, Gray TJ, Gibson GG. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1999 March; 29(3): 269-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219967&dopt=Abstract
78
Erythromycin
•
A systemic reaction following exposure to a pyrethroid insecticide. Author(s): Box SA, Lee MR. Source: Human & Experimental Toxicology. 1996 May; 15(5): 389-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8735461&dopt=Abstract
•
Abscesses due to mycobacterium abscessus linked to injection of unapproved alternative medication. Author(s): Galil K, Miller LA, Yakrus MA, Wallace RJ Jr, Mosley DG, England B, Huitt G, McNeil MM, Perkins BA. Source: Emerging Infectious Diseases. 1999 September-October; 5(5): 681-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10511524&dopt=Abstract
•
Accumulation of mitochondrial P450MT2, NH(2)-terminal truncated cytochrome P4501A1 in rat brain during chronic treatment with beta-naphthoflavone. A role in the metabolism of neuroactive drugs. Author(s): Boopathi E, Anandatheerthavarada HK, Bhagwat SV, Biswas G, Fang JK, Avadhani NG. Source: The Journal of Biological Chemistry. 2000 November 3; 275(44): 34415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10915793&dopt=Abstract
•
Activity of eleven kampo formulations and eight kampo crude drugs against Propionibacterium acnes isolated from acne patients: retrospective evaluation in 1990 and 1995. Author(s): Higaki S, Nakamura M, Morohashi M, Hasegawa Y, Yamagishi T. Source: The Journal of Dermatology. 1996 December; 23(12): 871-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9037918&dopt=Abstract
•
Effects of organic anions and vinblastine on biliary excretion of erythromycin in rats. Author(s): Sato A, Takikawa H, Yamanaka M. Source: Pharmacology. 1999 November; 59(5): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10529657&dopt=Abstract
•
Erythromycin and azithromycin transport into Haemophilus influenzae ATCC 19418 under conditions of depressed proton motive force (delta mu H). Author(s): Capobianco JO, Goldman RC. Source: Antimicrobial Agents and Chemotherapy. 1990 September; 34(9): 1787-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2178338&dopt=Abstract
•
Erythromycin, carbomycin, and spiramycin inhibit protein synthesis by stimulating the dissociation of peptidyl-tRNA from ribosomes. Author(s): Menninger JR, Otto DP.
Alternative Medicine 79
Source: Antimicrobial Agents and Chemotherapy. 1982 May; 21(5): 811-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6179465&dopt=Abstract •
Human MDR1 and mouse mdr1a P-glycoprotein alter the cellular retention and disposition of erythromycin, but not of retinoic acid or benzo(a)pyrene. Author(s): Schuetz EG, Yasuda K, Arimori K, Schuetz JD. Source: Archives of Biochemistry and Biophysics. 1998 February 15; 350(2): 340-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9473310&dopt=Abstract
•
Increased sensitivity to erythromycin in Escherichia coli associated with the presence of the ColV,I-K94 virulence plasmid. Author(s): Alfa CE, Reakes CF, Rowbury RJ. Source: Journal of Medical Microbiology. 1987 September; 24(2): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3309319&dopt=Abstract
•
Influence of cytostatic treatment on the efficacy of erythromycin and roxithromycin in a staphylococcal infection in mice. Author(s): Calame W, Guiot HF, Mattie H. Source: Scandinavian Journal of Infectious Diseases. 1990; 22(6): 717-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2149467&dopt=Abstract
•
Influence of etoposide and cyclophosphamide on the efficacy of cloxacillin and erythromycin in an experimental staphylococcal infection. Author(s): Calame W, van der Waals R, Mattie H, van Furth R. Source: Antimicrobial Agents and Chemotherapy. 1989 June; 33(6): 980-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2764550&dopt=Abstract
•
Interactions of ofloxacin and erythromycin with the multidrug resistance protein (MRP) in MRP-overexpressing human leukemia cells. Author(s): Terashi K, Oka M, Soda H, Fukuda M, Kawabata S, Nakatomi K, Shiozawa K, Nakamura T, Tsukamoto K, Noguchi Y, Suenaga M, Tei C, Kohno S. Source: Antimicrobial Agents and Chemotherapy. 2000 June; 44(6): 1697-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817732&dopt=Abstract
•
Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythraea. Author(s): Hessler PE, Larsen PE, Constantinou AI, Schram KH, Weber JM. Source: Applied Microbiology and Biotechnology. 1997 April; 47(4): 398-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9163954&dopt=Abstract
•
Predominance of serotype V and frequency of erythromycin resistance in Streptococcus agalactiae in Ohio. Author(s): Croak A, Abate G, Goodrum K, Modrzakowski M.
80
Erythromycin
Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1148-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748459&dopt=Abstract •
Protective effect of Livex, a herbal formulation against erythromycin estolate induced hepatotoxicity in rats. Author(s): Venkateswaran S, Pari L, Viswanathan P, Menon VP. Source: Journal of Ethnopharmacology. 1997 August; 57(3): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9292408&dopt=Abstract
•
Protective effect of Sesbania grandiflora against erythromycin estolate-induced hepatotoxicity. Author(s): Pari L, Uma A. Source: Therapie. 2003 September-October; 58(5): 439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14682193&dopt=Abstract
•
Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin. Author(s): O'Hara K, Kanda T, Ohmiya K, Ebisu T, Kono M. Source: Antimicrobial Agents and Chemotherapy. 1989 August; 33(8): 1354-7. Erratum In: Antimicrob Agents Chemother 1989 November; 33(11): 2025. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2478074&dopt=Abstract
•
Sensitive determination of erythromycin in human plasma by LC-MS/MS. Author(s): Li YX, Neufeld K, Chastain J, Curtis A, Velagaleti P. Source: Journal of Pharmaceutical and Biomedical Analysis. 1998 February; 16(6): 96170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9547699&dopt=Abstract
•
Systemic bioavailability of erythromycin in cattle when applied by footbath. Author(s): Hartog BJ, Tap SH, Pouw HJ, Poole DA, Laven RA. Source: The Veterinary Record. 2001 June 23; 148(25): 782-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465266&dopt=Abstract
•
The effect of erythromycin on gastric emptying is modified by physiological changes in the blood glucose concentration. Author(s): Jones KL, Kong MF, Berry MK, Rayner CK, Adamson U, Horowitz M. Source: The American Journal of Gastroenterology. 1999 August; 94(8): 2074-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445530&dopt=Abstract
•
Utilization of Egyptian raw by-products for the erythromycin production by Streptomyces erythreus. Author(s): Osman HG, Abou-Zeid AA, el-Gamal AA.
Alternative Medicine 81
Source: Z Allg Mikrobiol. 1968; 8(5): 429-35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4989340&dopt=Abstract •
Vinblastine and erythromycin: an unrecognized serious drug interaction. Author(s): Tobe SW, Siu LL, Jamal SA, Skorecki KL, Murphy GF, Warner E. Source: Cancer Chemotherapy and Pharmacology. 1995; 35(3): 188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7805175&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/
•
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
•
Chinese Medicine: http://www.newcenturynutrition.com/
•
drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
•
Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
•
Google: http://directory.google.com/Top/Health/Alternative/
•
Healthnotes: http://www.healthnotes.com/
•
MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
•
Open Directory Project: http://dmoz.org/Health/Alternative/
•
HealthGate: http://www.tnp.com/
•
WebMD®Health: http://my.webmd.com/drugs_and_herbs
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to erythromycin; 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 Acne Vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Conjunctivitis and Blepharitis Source: Healthnotes, Inc.; www.healthnotes.com
82
Erythromycin
Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com Lyme Disease Source: Integrative Medicine Communications; www.drkoop.com Pharyngitis Source: Integrative Medicine Communications; www.drkoop.com Pyloric Stenosis Source: Integrative Medicine Communications; www.drkoop.com Sore Throat Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com Amoxicillin Source: Healthnotes, Inc.; www.healthnotes.com Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Antibiotics (general) Source: Prima Communications, Inc.www.personalhealthzone.com Azithromycin Source: Healthnotes, Inc.; www.healthnotes.com Benzamycin Source: Healthnotes, Inc.; www.healthnotes.com Brewer's Yeast Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: Healthnotes, Inc.; www.healthnotes.com Erythromycin Source: Healthnotes, Inc.; www.healthnotes.com Macrolides Source: Healthnotes, Inc.; www.healthnotes.com Macrolides Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 83
Neomycin Source: Healthnotes, Inc.; www.healthnotes.com Penicillamine Source: Healthnotes, Inc.; www.healthnotes.com Penicillin V Source: Healthnotes, Inc.; www.healthnotes.com Probiotics Source: Healthnotes, Inc.; www.healthnotes.com Quinidine Source: Healthnotes, Inc.; www.healthnotes.com Red Yeast Rice Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
85
CHAPTER 4. DISSERTATIONS ON ERYTHROMYCIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to erythromycin. 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 “erythromycin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on erythromycin, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Erythromycin 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 erythromycin. 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: •
Enzymatic and Structural Study of Domains and Modules from Erythromycin and Picromycin Polyketide Synthases by Lu, Hongxiang; PhD from Brown University, 2003, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3087303
•
Synthons for the Construction of Erythromycin by Castelhano, Arlindo Lucas; PhD from McMaster University (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK52211
•
Transformation Reactions of Erythromycin in Superheated Water and Their Implications for Microbial Resistance by Butler, Michelle Nicol; PhD from University of Michigan, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3096059
86
Erythromycin
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.
87
CHAPTER 5. CLINICAL TRIALS AND ERYTHROMYCIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning erythromycin.
Recent Trials on Erythromycin The following is a list of recent trials dedicated to erythromycin.8 Further information on a trial is available at the Web site indicated. •
The inhibition of platelet antiaggregating activity of clopidogrel by atorvastatin detected by erythromycin breath test: a metabolic inhibition of hepatic cytochrome P450-3A Condition(s): Hypercholesterolemia; Thrombosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The objective of this study is to determine if the action of the drug called clopidogrel, that you will start taking, will be decreased by another drug called atorvastatin, that you will also start taking. Clopidogrel is an oral antiplatelet agent that has been shown to prevent strokes and heart attacks. Atorvastatin is a cholesterol lowering agent. Twenty adults 18-75 years of age requiring cholesterol-lowering agent and antiplatelet agent therapy will be recruited for this study during their cardiology clinic visitation. In one group, antiplatelet agent (clopidogrel) regimen will be administered first, then followed by cholesterol-lowering medication (atorvastatin). In the second group, atorvastatin will be administered first, followed by clopidogrel. A new test called the erythromycin breath test will be administered to you three times during the study to measure how your liver will metabolize these drugs. Blood samples will also be obtained to assess platelet function. The criteria for exclusion are patient refusal or inability to give written consent, patients with allergic reaction to erythromycin, patients with known bleeding problems, liver disease, significant lung
8
These are listed at www.ClinicalTrials.gov.
88
Erythromycin
disease kidney disease and pregnancy. Patients with psychiatric impairment and documented history of substance abuse will also be excluded from the study. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004564
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 “erythromycin” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
•
For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
•
For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
•
For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
•
For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
•
For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
•
For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
•
For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
•
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
Clinical Trials 89
•
For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
•
For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
•
For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
•
For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
•
For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
91
CHAPTER 6. PATENTS ON ERYTHROMYCIN 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 “erythromycin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on erythromycin, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Erythromycin By performing a patent search focusing on erythromycin, 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.
92
Erythromycin
example of the type of information that you can expect to obtain from a patent search on erythromycin: •
3',3'-N-bis-desmethyl-3'-N-cycloalkyl erythromycin derivatives as LHRH antagonists Inventor(s): Bruncko; Milan (Lake Bluff, IL), Dalton; Christopher R. (Mundelein, IL), Frey; Lisa M. (Mundelein, IL), Haviv; Fortuna (Deerfield, IL), Kaminski; Michele A. (Beach Park, IL), Sauer; Daryl R. (Trevor, WI) Assignee(s): Abbott Laboratories (abbott Park, Il) Patent Number: 6,387,885 Date filed: August 26, 1998 Abstract: Disclosed are 3',3'-N-bis-desmethyl-3'-N-cycloalkyl-6-O-methyl-11-deoxy11,12-cyclic carbamate erythromycin A derivatives which are antagonists of lutenizing hormone-releasing hormone (LHRH). Also disclosed are pharmaceutical compositions comprising the compounds, to methods of using the compounds and to the process of making the same. Excerpt(s): The present invention relates to a class of macrolide compounds which are antagonists of lutenizing hormone-releasing hormone (LHRH), to pharmaceutical compositions comprising the compounds, to methods of using the compounds and to the process of making the same. More particularly, the present invention relates to 3',3'N-bis-desmethyl-3'-N-cycloalkyl-6-O-methyl-11-deoxy-11,12-cyclic carbamate erythromycin A derivatives which are antagonists of LHRH. The gonadotropins, follicle stimulating hormone (FSH), lutenizing hormone (LH), and chorionic gonadotropin (CG) are required for ovulation, spermatogenesis, and the biosynthesis of sex steroids. A single hypothalamic hormone, gonadotropin-releasing hormone GnRH also known as LHRH is responsible for regulating the secretion of both FSH and LH in mammals. where the superscripts designate the position of each aminoacyl residue in the decapeptide chain. Web site: http://www.delphion.com/details?pn=US06387885__
•
6-O-aklyl erythromycin B oxime Inventor(s): Liu; Jih-Hua (Green Oaks, IL), Montgomery; Stephen H. (Vernon Hills, IL) Assignee(s): Abbott Laboratories (abbott Park, Il) Patent Number: 6,194,387 Date filed: April 29, 1999 Abstract: A process of preparing a 6-O-alkyl derivative of 9-oxime erythromycin B is provided. Intermediates used in the preparation of a 6-O-alkyl 9-oxime erythromycin B are also provided. Pharmaceutical compositions containing a 6-O-alkyl derivative of 9oxime erythromycin B and the use of those compositions to treat bacterial infections are also provided. Excerpt(s): The present invention relates to erythromycin derivatives. More particularly, the present invention pertains to 6-O-alkyl derivatives of 9-oxime erythromycin B, a process for making those compounds and the use of the compounds as antibiotics. where R.sup.1 is alkyl, R.sup.2 and R.sup.4 are each independently hydrogen or a conventional O-protecting group, and R.sup.3 is --NR.sup.5 (CH.sub.3).sub.2, where
Patents 93
R.sup.5 is methyl (CH.sub.3) or a conventional N-protecting group or --N.sup.+ (CH.sub.3).sub.2 R.sup.6 X.sup.-, where R.sup.6 is 2-alkenyl, benzyl or substituted benzyl, and X is a halogen. In a preferred embodiment, R.sup.1 is methyl, R.sup.2 and R.sup.4 are both hydrogen and R.sup.3 is dimethylamine. The synthetic process for making a 6-O-alkyl derivative of 9-oxime erythromycin B starts with conversion of erythromycin B (a fermentation product) to 2'-acetyl erythromycin B. That conversion is accomplished by reacting erythromycin B with an acetylating reagent such as acetic anhydride. 2'-Acetyl erythromycin B is then alkylated at the 6-hydroxyl to provide a 2'acetyl-6-O-alkyl erythromycin B. Alkylation of the 6-hydroxyl group is accomplished using an alkylating reagent such as an alkyl halide or an alkyl sulfate. The 2'-acetyl-6-Oalkyl erythromycin B is then oximated and deacetylated to form 6-O-alkyl-9-oxime erythromycin B. Web site: http://www.delphion.com/details?pn=US06194387__ •
Anti-cancer products for treating cystic fibrosis Inventor(s): Annereau; Jean-Philippe (Paris, FR), Barthe; Joel (Paris, FR), Blanquet; Sylvain (Paris, FR), Lallemand; Jean-Yves (Palaiseau, FR), Lenoir; Gerard (Paris, FR), Stoven; Veronique (Paris, FR) Assignee(s): Centre National DE LA Recherche Scientifique (cnrs) (paris, Fr) Patent Number: 6,635,627 Date filed: November 29, 1999 Abstract: The invention concerns a novel approach for treating cystic fibrosis using, in particular, anti-cancer chemotherapy. For the treatment of cystic fibrosis it proposes the use of at least one product which when administered to a patient brings about the expression or overexpression of an ABC carrier compound, in particular glutathione carrier. Preferably, the products used are anti-cancer products whose administration brings about the expression of MRP and/or MDR protein. The invention is also applicable to the treatment of rheumatoid polyarthritis or asthma. More specifically, the compounds are selected among cyclophosphamide, aclarubicin, doxorubicin, daunorubicin, epirubicin, idarubicin, zorubicin, pirabucin, colchicine, videsine, vinorelbine, vincristine, binblasine, azithromycin, erythromycin, ifosmamide, N-acetyl cysteine, N-acetyl lysine and/or a CFTR protein fragment comprising the NBF1 domain. Excerpt(s): This Application is a 371 of PCT/FR98/01074 filed May 28, 1998, which claims priority from France 97/06667 filed May 30, 1997. The present invention relates to a novel approach for treating cystic fibrosis which involves chemotherapy, in particular anticancer chemotherapy. Cystic fibrosis is a genetic disease which is expressed in particular in the lungs and which is due to a defect in the gene encoding the CFTR (standing for "Cystic Fibrosis Transmembrane Conductance Regulator") protein, which is a protein which is able to participate directly or indirectly in the transport of chloride ions across the cell membranes. Web site: http://www.delphion.com/details?pn=US06635627__
94
•
Erythromycin
Cyclobutene derivatives useful as antagonists of the motilin receptor Inventor(s): Chen; Robert H. (Belle Mead, NJ), Xiang; Min A. (Bridgewater, NJ) Assignee(s): Ortho-mcneil Pharmaceutical, Inc. (raritan, Nj) Patent Number: 6,384,031 Date filed: March 9, 2001 Abstract: The compounds of formula I are useful in treating gastrointestinal disorders associated with antagonizing the motilin receptor. The compounds compete with erythromycin and motilin for the motilin receptor. In addition the compounds are antagonists of the contractile smooth muscle response to those ligands. Excerpt(s): This invention relates to a series of novel cyclobutene derivatives, pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention are useful as non-peptidyl antagonists of the motilin receptor. In addition, the compounds display efficacy and potency which are comparable to known motilin and erythromycin antagonists. In mammals, the digestion of nutrients and the elimination of waste is controlled by the gastrointestinal system. This system is, to say the least, complicated. There are a number of natural peptides, ligands, enzymes, and receptors which play a vital role in this system and are potential targets for drug discovery. Modifying the production of, or responses to these endogenous substances can have an effect upon the physiological responses such as diarrhea, nausea, and abdominal cramping. One example of an endogenous substance which affects the gastrointestinal system is motilin. Motilin is a peptide of 22 amino acids which is produced in the gastrointestinal system of a number of species. Although the sequence of the peptide varies from species to species, there are a great deal of similarities. For example, human motilin and porcine motilin are identical; while motilin isolated from the dog and the rabbit differ by five and four amino acids, respectively. Motilin induces smooth muscle contractions in the stomach tissue of dogs, rabbits, and humans as well as in the colon of rabbits. Apart from local gastrointestinal intestinal tissues, motilin and its receptors have been found in other tissues. For example, motilin has been found in circulating plasma, where a rise in the concentration of motilin has been associated with gastric effects which occur during fasting in dogs and humans (Itoh, Z. et al., 1976, Scand. J. Gastroenterol. 11:93-110; Vantrappen, G. et al. Dig., 1979, Dis Sci 24, 497-500). In addition, when motilin was intravenously administered to humans it was found to increase gastric emptying and gut hormone release (Christofides, N. D. et al., 1979, Gastroenterology 76:903-907). Web site: http://www.delphion.com/details?pn=US06384031__
•
Derivatives of erythromycin, clarithromycin, roxithromycin or azithromycin with antibiotic and mucolytic activity Inventor(s): Hermann; Gesine (Cork, IE), Nikolopoulos; Aggelos (Cork, IE), Schickaneder; Helmut (Cork, IE) Assignee(s): Russinsky Limited (cork, Ie) Patent Number: 6,599,885 Date filed: April 19, 2001 Abstract: A pharmaceutical with an enhanced pharmaceutical profile comprises a mucolytic and an antibiotic in which the mucolytic is present in an amount of greater
Patents 95
than one molar equivalent of the antibiotic. The antibiotic may be selected from Erythromycin, Roxithromycin, Clarithromycin, Azithromycin, Dirithromycin; and pharmaceutically acceptable salts or esters thereof. The mucolytic is a mucolytically active thiol, especially N-acetylcysteine, mercaptoethanesulfonic acid, tiopronin or methylcysteine. The adducts can be isolated via a simple and efficient process. Excerpt(s): The invention relates to a pharmaceutical including a macrolide antibiotic. The invention also relates to a process for manufacturing the pharmaceutical. It is known that the stability and the pharmacological and immunomicrobiological profile of these compounds can be improved by derivatisation and by conversion into various salts. There is a need for a pharmaceutical including a macrolide antibiotic which will have an enhanced pharmaceutical profile. Web site: http://www.delphion.com/details?pn=US06599885__ •
Erthromycin a oxime solvates Inventor(s): Bosch; Immaculada (Vic/Barcelona, ES), Centellas; Victor (Cardedeu/Barcelona, ES), Diago; Jose (Granollers/Barcelona, ES) Assignee(s): Biochemie S.a. (granollers/barcelona, Es) Patent Number: 6,504,017 Date filed: January 4, 2000 Abstract: Erythromycin A oxime in the form of a hemihydrate. Excerpt(s): The present invention relates to the synthesis of antibacterial macrolides, such as of the erythromycin, for example erythromycin A, type, e.g. roxithromycin, dirithromycin, clarithromycin, azithromycin and similar compounds. hereinafter designated as erythromycin A oxime. Erythomycin A is a well known, e.g. antibacterial agent. Isolated erythromycin A oxime, e.g. in free-base form obtained according to known processes may be obtained in unstable form, e.g. it may be hygroscopic. We have now found erythromycin A oxime in free-base form in stable, e.g. non hygroscopic form, e.g. a compound according to the present invention may keep a constant water content under normal, e.g. normal air humidity, environmental conditions for at least 24 hours. in the form of a hemihydrate. Web site: http://www.delphion.com/details?pn=US06504017__
•
Erythromycin a compounds and process for preparing the same Inventor(s): Kim; Nam-Du (Kyunggi-do, KR), Lee; Gwan-Sun (Seoul, KR), Pae; HyoungJun (Kyunggi-do, KR), Suh; Kwee-Hyun (Kyunggi-do, KR) Assignee(s): Hanmi Pharmaceutical Co., Ltd. (kyunggi-do, Kr) Patent Number: 6,528,628 Date filed: June 29, 2001 Abstract: A new erythromycin A 9-oxime compound which can be effectively used as intermediates for the preparation of erythromycin A oxime compound, a process for preparing the same and a process for preparing 6-O-alkyl erythromycin A or its oxime using the same is described.
96
Erythromycin
Excerpt(s): The present invention relates to a new erythromycin A 9-oxime compound which can effectively be used as an intermediate for the preparation of 6-O-alkyl erythromycin A such as 6-O-methyl erythromycin A (hereinafter referred to as "clarithromycin") or its oxime, a process for preparing the same and a process for preparing 6-O-alkyl erythromycin A or its oxime using the same. 6-O-alkyl erythromycin A is a semi-synthetic macrolide antibacterial agent showing an excellent antibacterial activity against a number of bacteria which can cause diseases in human or mammals, for example, gram-positive bacteria, a part of gram-negative bacteria, anaerobic bacteria, Mycoplasma, and Chlamidia, etc., and also can be used as a raw material for the synthesis of other antibiotic in this field, and it therefore is a pharmaceutically important material. 6-O-alkyl erythromycin A compound including 6O-methyl erythromycin A can be prepared by selectively alkylating the 6-position of suitably protected erythromycin A 9-oxime, eliminating the protecting groups and then carrying out deoximation. Since erythromycin A 9-oxime has a number of reactive hydroxy groups including the hydroxy group of oxime and a dimethylamino group at the 3' position which can also participate in alkylation, it is very important to carry out alkylation of the hydroxy group at the 6 position after protecting these groups with suitable substituents. Web site: http://www.delphion.com/details?pn=US06528628__ •
Erythromycin derivatives with antibiotic activity Inventor(s): Albini; Enrico (Pavia, IT), Botta; Daniela (Como, IT), Pellacini; Franco (Milan, IT), Ungheri; Domenico (Parabiago, IT) Assignee(s): Zambon Group S.p.a. (vicenza, It) Patent Number: 6,468,979 Date filed: January 30, 2001 Abstract: Erythromycin derivatives with antibiotic activity and pharmaceutically acceptable salts thereof. A process for preparing such erythromycin derivatives and pharmaceutical compositions containing them as the active principle. Excerpt(s): in which Het is a biheterocyclic system; to pharmaceutically acceptable salts thereof and to pharmaceutical compositions containing them as active principle. A is a phenyl or a 5- or 6-membered heterocycle containing one or more hetero atoms chosen from nitrogen, oxygen and sulphur, optionally substituted with 1 to 3 groups, which are the same or different and are chosen from linear or branched C.sub.1 -C.sub.4 alkyl or alkoxy groups, C.sub.1 -C.sub.2 cycloalkenedioxy groups, C.sub.1 -C.sub.4 alkylsulphonyl groups, phenyl, phenoxy, hydroxyl, carboxyl, nitro, halo and trifluoromethyl groups; R.sub.1 and R.sub.2 are the same or different hydrogen atom or linear or branched C.sub.1 -C.sub.4 alkyl group; n is 1 or 2; m is an integer from 1 to 8; r is an integer from 2 to 6; R.sub.3 is hydrogen or methyl. We have now found that, by introducing a biheterocyclic group as a substituent (-A) at the end of the chain in the compounds of formula (II) of the above-mentioned international patent application, it is possible to obtain a class of erythromycin derivatives which have a particularly broad spectrum of activity and a long duration of action, thereby making them extremely useful in antibiotic therapy. Web site: http://www.delphion.com/details?pn=US06468979__
Patents 97
•
Erythronolide compounds Inventor(s): McDaniel; Robert (Palo Alto, CA) Assignee(s): Kosan Biosciences, Inc. (hayward, Ca) Patent Number: 6,403,775 Date filed: October 28, 1999 Abstract: Genetic engineering of the erythromycin polyketide synthase genes to effect combinatorial alterations of catalytic activities in the biosynthetic pathway can be used to generate a library of macrolides impractical to produce by chemical methods. The library includes examples of analogs with one, two and three altered carbon centers of the polyketide products. Excerpt(s): This application is related to U.S. Ser. No. 09/073,538, filed May 6, 1998, which is a continuation-in-part of U.S. Ser. No. 08/846,247, filed Apr. 30, 1997, and is related to PCT application No. U.S. Ser. No. 98/08792 and U.S. provisional application Serial No. 60/076,919, filed Mar. 5, 1998, now lapsed. The present invention provides recombinant DNA compounds and host cells containing novel polyketide synthase (PKS) genes and novel polyketides. The invention relates to the fields of chemistry, medicinal chemistry, human and veterinary medicine, molecular biology, pharmacology, agriculture, and animal husbandry. Few molecules have captured interest in both chemotherapy and chemistry to the extent of the polyketide erythromycin and its semi-synthetic derivatives. Erythromycin and its congeners are the third most widely used class of antibiotics, with current worldwide sales exceeding US $3.5 billion. In addition, erythromycin analogs are gaining interest for their potential use in the treatment of gastrointestinal disorders (Omura, "The expanded horizon for microbial metabolites--a review," Gene 115, 141-149 (1992)), inflammatory diseases (Kawasaki et al., "Roxithromycin inhibits cytokine production by and neutrophil attachment to human bronchial epithelial cells in vitro," Antimicrob. Agents Chemother. 42, 1499-1502 (1998)), and as next-generation antibiotics for treatment of emerging drugresistant strains of bacteria (Agoudiras et al., "In-vitro antibacterial activity of RU 004 (HMR 3004), a novel ketolide derivative active against respiratory pathogens," Antimicrob. Agents Chemother. 41, 2149-2158 (1997)). Web site: http://www.delphion.com/details?pn=US06403775__
•
Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin Inventor(s): Allaudeen; HameedSulthan S. (Durham, NC), Ekwuribe; Nnochiri Nkem (Cary, NC), Radhakrishnan; Balasingam (Chapel Hill, NC), Ramaswamy; Muthukumar (Cary, NC) Assignee(s): Protein Delivery, Inc. (durham, Nc) Patent Number: 6,191,105 Date filed: October 27, 1997 Abstract: A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin,
98
Erythromycin
calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications. Excerpt(s): The present invention relates to microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents, and to methods of making and using same. The compositions of the invention may comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhythmics, anti-coagulants, etc., and prodrugs, precursors, derivatives, and intermediates thereof. In the field of pharmaceutical therapeutic intervention, and the treatment of disease states and physiological conditions, a wide variety of therapeutic agents have come into use, including various proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhythmics, anti-coagulants, etc., and prodrugs precursors, derivatives, and intermediates of the foregoing. For example, the use of polypeptides and proteins for the systemic treatment of specific diseases is now well accepted in medical practice. The role that the peptides play in replacement therapy is so important that many research activities are being directed towards the synthesis of large quantities by recombinant DNA technology. Many of these polypeptides are endogenous molecules which are very potent and specific in eliciting their biological actions. Other non-(poly)peptidyl therapeutic agents are equally important and pharmaceutically efficacious. Web site: http://www.delphion.com/details?pn=US06191105__ •
Macrolides Inventor(s): Blize; Alan Elwood (New London, CT), Dirlam; John Philip (Gales Ferry, CT), McArthur; Hamish Alastair Irvine (Mystic, CT) Assignee(s): Pfizer, Inc. (new York, Ny) Patent Number: 6,472,371 Date filed: May 23, 2000 Abstract: The invention relates to novel erythromycin analogs and azalides, particularly ones with novel C-13 substituents, and to pharmaceutically acceptable salts thereof. The compounds of this invention are antibacterial agents that may be used to treat various bacterial and protozoa infections. The invention also relates to pharmaceutical compositions containing such compounds and to methods of treating bacterial protozoa
Patents 99
infections by administering such compounds. The invention also relates to methods of preparing such compounds and to intermediates useful in such preparation. Excerpt(s): Macrolide antibiotics are known to be useful In the treatment of a broad sprectrum of bacterial infections and protozoa infections in mammals, fish and birds. Such antibiotics include various derivatives of erythromycin A such as azithromycin which is commercially available and is referred to in U.S. Pat. Nos. 4,474,768 and 4,517,359, both of which are incorporated herein by reference in their entirety. Additional macrolides are referred to in U.S. patent application serial No. 60/063676, filed Oct. 29, 1997 (Yong-Jin Wu), U.S. application serial No. 60/053161, filed Oct. 29, 1997 (Yong-Jin Wu), U.S. application serial No. 60/054866, filed Aug. 6, 1997 (Hiroko Masamune, Yong-Jin Wu, Takushi Kaneko and Paul R. McGuirk), U.S. application serial No. 60/049980, filed Jun. 11, 1997 (Brian S. Bronk, Michael A. Latavik, Takushi Kaneko and Bingwel V. Yang), U.S. application serial No. 60/049348, filed Jun. 11, 1997 (Brian S. Bronk, Hengmiao Cheng, E. A. Glaser, Michael A, Letavic, Takushi Kaneko and Bingwei V. Yang), International Application No. PCT/GB97/01810 filed Jul. 4, 1997 (Peter Francis Leadlay, James Staunton, Jesus Cortes and Michael Stephen Pacey), International Application No. PCT/GB97/01819 filed Jul. 4, 1997 (Peter Francis Leadlay, James Staunton, and Jesus Cortes), U.S. application serial No. 60/070343, filed Jan. 2, 1998, (Diriam), U.S. application serial No. 60/070358, filed Jan. 2, 1998 (Yong-Jin Wu) and U.S. application serial No. 60/097075, filed Aug. 19, 1998 (Hengmiao Cheng, Michael A Letavic, Carl B. Ziegler, Jason K, Dutra, Brian S. Bronk), all of which are incorporated herein by reference in their entirety. Like azithromycin and other macrolide antibiotics, the novel macrolide compounds of the present invention possess potent activity against various bacterial infections and protozoa infections as described below. each R.sup.21 and R.sup.22 is independently H, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.8 alkenyl, (CH.sub.2).sub.m (C.sub.6 -C.sub.10) aryl, (CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, or C.sub.2 -C.sub.10 alkylyl. each R.sup.21 and R.sup.22 is independently H, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, (CH.sub.2).sub.m (C.sub.6 -C.sub.10) aryl, (CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, or C.sub.2 -C.sub.10 alkylyl. Web site: http://www.delphion.com/details?pn=US06472371__ •
Method for strain improvement of the erythromycin-producing bacterium Inventor(s): Luu; Minh B. (Chicago, IL), Weber; J. Mark (Chicago, IL) Assignee(s): Fermalogic Inc. (chicago, Il) Patent Number: 6,420,177 Date filed: September 15, 1998 Abstract: The present invention relates to a method of improving the strain used for the production of erythromycin through the disruption of the melA gene. Excerpt(s): The field of this invention is erythromycin production. More particularly, the present invention pertains to a method of improving the strain used for the production of erythromycin through the disruption of the melA gene. Actinomycete fermentations are the source of many medically important pharmaceuticals, particularly antibiotics. The commercial production of these compounds is made more economical through genetic alterations in the producing organism, referred to as strain improvements, that are traditionally introduced through a random mutation and screening process
100
Erythromycin
(Queener, S. W. and D. H. Lively 1986. Screening and selection for strain improvement, p. 155-169. In Manual of Industrial Microbiology and Biotechnology. Eds. A. L. Demain and N. A. Solomon. American Society for Microbiology, Washington. 1986). The traditional process is tedious and time consuming, but is technically simple to perform. Its major drawback is that it is empirical; and during the 50 years that it has been practiced by industry, very little has been learned concerning the genetics of strain improvement. More recently molecular genetic technology has been developed that allows for the introduction of "targeted" genetic alterations of industrially important strains. In particular, the erythromycin producing strain, Sac. erythraea, has a well developed system for integrative transformation, targeted gene replacement and disruption (Weber, J. M. and R. Losick, 1988, Gene 68, 173-180; Weber, J. M., J. O. Leung, G. T. Maine, R H. B. Potenz, T. J. Paulus and J. P. DeWitt, 1990, J. Bacteriol. 172, 23722383). This approach, though technically more difficult to perform, provides yield improvement results plus insight into the metabolic and genetic events that lead to strain improvement. Web site: http://www.delphion.com/details?pn=US06420177__ •
Method of preparing form II crystals of clarithromycin Inventor(s): Kim; Gi-Jeong (Seoul, KR), Kim; Nam-Du (Kyungki-do, KR), Lee; GwanSun (Seoul, KR), Seong; Mi-Ra (Kyungki-do, KR), Suh; Kwee-Hyun (Kyungki-do, KR), Yun; Sang-Min (Kyungki-do, KR) Assignee(s): Hanmi Pharm. Co., (kr) Patent Number: 6,515,116 Date filed: March 14, 2001 Abstract: High purity Form II crystals of clarithromycin can be easily prepared in a high yield by a process comprising the steps of: protecting the 9-oxime hydroxy group of erythromycin A 9-oxime or a salt thereof with a tropyl group and the 2'- and 4"-hydroxy groups with trimethylsilyl groups; reacting 2',4"-O-bis(trimethylsilyl)erythromycin A 9O-tropyloxime with a methylating agent; removing the protecting groups and the oxime group of 2',4"-O-bis(trimethylsilyl)-6-O-methylerythromycin A 9-O-tropyloxime to obtain crude clarithromycin; treating the crude clarithromycin with methanesulfonic acid in a mixture of a water-miscible organic solvent and water to obtain crystalline clarithromycin mesylate trihydrate; and neutralizing the crystalline clarithromycin mesylate trihydrate with aqueous ammonia in a mixture of a water-miscible organic solvent and water. Excerpt(s): The present invention relates to a method of preparing Form II crystals of clarithromycin; and to novel intermediates used in said method. It has been reported that clarithromycin exists in at least three distinct crystalline forms, "Form 0", "Form I" and "Form II" (International Publication Nos. WO 98/04573 and WO 98/31699). The crystal forms can be identified by infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectrophotometry. Form II, which is thermodynamically more stable than Form I, is used in the drug formulations currently on the market. Various methods for preparing clarithromycin have been reported, e.g., in EP Patent Nos. 0,147,062, 0,158,467, 195,960 and 260,938; and U.S. Pat. Nos. 4,990,602, 5,837,829, 5,929,219, 5,892,008, 5,864,023 and 5,852,180. The most widely used methods use an erythromycin A 9-oxime derivative as an intermediate, which are described below.
Patents 101
Web site: http://www.delphion.com/details?pn=US06515116__ •
Polyketide derivatives and recombinant methods for making same Inventor(s): Kakavas; Stephan J. (Buffalo Grove, IL), Katz; Leonard (Wheeling, IL), Pereda-Lopez; Ana (Mundelein, IL), Ruan; Xiaoan (Lake Bluff, IL), Stassi; Diane L. (Highland Park, IL), Summers, Jr.; Richard G. (Nashotah, WI) Assignee(s): Abbott Laboratories (abbott Park, Il) Patent Number: 6,200,813 Date filed: December 23, 1997 Abstract: The invention provides novel erythromycin derivatives in which methyl groups on the macrolactone ring have been substituted with --H, -Et, and/or --OH. The invention also provides reagents such as isolated polynucleotides, vectors comprising the polynucleotides and host cells transformed with the vectors for making the novel compounds. Methods for making the compounds utilizing genetic engineering techniques are also disclosed. Excerpt(s): The present invention relates to novel polynucleotide sequences, proteins encoded therefrom which are involved in the biosynthesis of polyketides, methods for directing the biosynthesis of novel polyketides using those polynucleotide sequences and novel derivatives produced therefrom. In particular, the invention relates to the production of novel polyketide derivatives through manipulation of the genes encoding polyketide synthases. Polyketides are a large class of natural products that includes many important antibiotic, antifungal, anticancer, antihelminthic, and immunosuppressant compounds such as erythromycins, tetracyclines, amphotericins, daunorubicins, avermectins, and rapamycins. Their synthesis proceeds by an ordered condensation of acyl esters to generate carbon chains of varying length and substitution pattern that are later converted to mature polyketides. This process has long been recognized as resembling fatty acid biosynthesis, but with important differences. Unlike a fatty acid synthase, a typical polyketide synthase is programmed to make many choices during carbon chain assembly: for example, the choice of "starter" and "extender" units, which are often selected from acetate, propionate or butyrate residues in a defined sequence by the polyketide synthase. The choice of using a full cycle of reduction-dehydration-reduction after some condensation steps, omitting it completely, or using one of two incomplete cycles (reduction alone or reduction followed by dehydration) is additionally programmed, and determines the pattern of keto or hydroxyl groups and the degree of saturation at different points in the chain. Finally, the stereochemistry for the substituents at many of the carbon atoms is programmed by the polyketide synthase. Streptomyces and the closely related Saccharopolyspora genera are producers of a prodigious diversity of polyketide metabolites. Because of the commercial significance of these compounds, a great amount of effort has been expended in the study of Streptomyces and Saccharopolyspora genetics. Consequently, much is known about these organisms and several cloning vectors and techniques exist for their transfornation. Web site: http://www.delphion.com/details?pn=US06200813__
102
•
Erythromycin
Process for preparing 6-o-substituted erythromycin derivatives Inventor(s): Cink; Russell D. (Grayslake, IL), Cooper; Arthur J. (Lake Villa, IL), Deshpande; Mahendra N. (Gurnee, IL), Grieme; Tim (Chicago, IL), Haight; Anthony R. (Wadsworth, IL), Hill; David R. (Gurnee, IL), Hsu; Margaret Chi-Ping (Vernon Hills, IL), King; Steven A. (Gurnee, IL), Ku; Yi-Yin (Buffalo Grove, IL), Leanna; Marvin Robert (Grayslake, IL), Lee; Elaine C. (Mundelein, IL), McLaughlin; Maureen A. (Evanston, IL), Morton; Howard E. (Gurnee, IL), Napier; James J. (Antioch, IL), Peterson; Matthew J. (Gurnee, IL), Plata; Daniel J. (Wadsworth, IL), Raje; Prasad S. (Lindenhurst, IL), Rasmussen; Michael (Kenosha, WI), Riley; David (Kenosha, WI), Stoner; Eric J. (Kenosha, WI), Tien; Jien-Heh J. (Vernon Hills, IL), Wittenberger; Steven J. (Mundelein, IL) Assignee(s): Abbott Laboratories (abbott Park, Il) Patent Number: 6,437,106 Date filed: March 3, 2000 Abstract: In one aspect, the invention relates to a process for preparing 6-O-substituted erythromycin derivatives comprising reacting 2'-substituted and optionally 4"substituted 9-oxime erythromycin derivatives with an alkylating agent in the presence of a palladium catalyst and phosphine. In another aspect, the invention relates to processes for preparing 6-O-substituted erythromycin ketolides using the palladiumcatalyzed alkylation reaction. Excerpt(s): The present invention relates to a process for preparing 6-O-substituted erythromycin derivatives and 6-O-substituted erythromycin ketolides thereof. Specifically, the invention relates to a palladium-catalyzed process for preparing 6-Osubstituted erythromycin derivatives from erythromycins using alkylating agents in presence of a phosphine and their subsequent conversion into 6-O-substituted erythromycin ketolides. 6-O-Methylerythromycin A (clarithromycin) is a potent macrolide antibiotic disclosed in U.S. Pat. No. 4,331,803. Step 4: deprotect at the 2', 4" and 9-positions. Web site: http://www.delphion.com/details?pn=US06437106__
•
Process for the preparation of 6-O-propargyl erythromycin derivatives Inventor(s): Bhagavatula; Lakshmi (Vernon Hills, IL), Chang; Sou-Jen (Prairie View, IL), Kerdesky; Francis A. J. (Grayslake, IL), King; Steven A. (Gurnee, IL), Lallaman; John E. (Zion, IL), Morton; Howard E. (Gurnee, IL), Pease; Jonathan P. (Antioch, IL), Premchandran; Ramiya (Gurnee, IL), Wayne; Gregory S. (Vernon Hills, IL) Assignee(s): Abbott Laboratories (abbott Park, Il) Patent Number: 6,605,707 Date filed: March 23, 2000 Abstract: Disclosed herein is a process for the preparation of erythromycin derivatives, or pharmaceutically acceptable salts thereof, which contain an optionally substituted propargyl group at the 6-O-position. Excerpt(s): The instant invention relates to a process for the preparation of erythromycin derivatives, or pharmaceutically acceptable salts thereof, which contain an optionally substituted propargyl group at the 6-O-position. Macrolide antibacterial agents are widely used to treat and prevent bacterial infections. However, the discovery of
Patents 103
bacterial strains which have resistance or insufficient susceptibility to these agents has promoted development of compounds with modified or improved profiles of antibiotic activity. Commonly owned U.S. Pat. No. 5,866,549 and commonly owned pending U.S. application Ser. No. 09/273,140, filed Mar. 19, 1999, teach the small scale syntheses of 6O-propargyl erythromycin derivatives. Large scale production of the same, however, requires a process which avoids complicating factors such as chromatography of intermediates and low-yielding steps, i.e., problems usually associated with macrolide or ketolide synthesis due to the number of reactive groups on the molecule. Web site: http://www.delphion.com/details?pn=US06605707__ •
Topical administration of antimicrobial agents for the treatment of systemic bacterial diseases Inventor(s): Stehle; Randall G. (Kalamazoo, MI), Watts; Jeffrey L. (Portage, MI) Assignee(s): Pharmacia & Upjohn Company (kalamazoo, Mi) Patent Number: 6,191,143 Date filed: March 17, 1999 Abstract: The present invention provides a method of topically administering antimicrobial agents such as premafloxacin, premafloxacin-like compound, premafloxacin ester, ciprofloxacin, enrofloxacin, cefquinome, cefpodoxime, gentamicin or erythromycin for the treatment of systemic bacterial diseases in mammals. Excerpt(s): The present invention relates to a method of topically administering antimicrobial agents for the treatment of systemic bacterial diseases in mammals. It has been generally accepted that intravenous infusion, intramuscular injection, subcutaneous, buccal, oral, and rectal routes are the methods for administration of a wide variety of antimicrobial agents for the treatment of systemic bacterial diseases. Due to lack of systemic level effects with antimicrobial agents administered topically, the topical administration of antimicrobial agents has been limited to the treatment of localized infections of the skin or eyes. However, it is known that the aforementioned non-topical methods of administration for the treatment of systemic bacterial diseases have certain disadvantages. For example, buccal and rectal administration often produce discomfort and aggravation to the mammals that are treated. The intravenous, subcutaneous and intramuscular routes are not only painful, but also must be performed by trained individuals. In addition, there is a risk of needle injury, infection, and other trauma including the emotional trauma inevitably associated with injections. Oral administration, although generally acceptable, may have the disadvantages of poor absorption of the therapeutic agent from the gastrointestinal tract and/or degradation which may be caused by the acidic medium of the stomach, or causes digestive disfunction in ruminants. Furthermore, in the case of treating animals, the aforementioned methods of administration are labor and time consuming. Topical administration of antimicrobial agents would circumvent these problems by allowing a more convenient, non-invasive method for the treatment of systemic bacterial diseases. Web site: http://www.delphion.com/details?pn=US06191143__
104
Erythromycin
Patent Applications on Erythromycin 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 erythromycin: •
11-C-substituted ketolides Inventor(s): Farmer, Jay Judson; (New Haven, CT), Or, Yat Sun; (Watertown, MA), Phan, Ly Tam; (Malden, MA) Correspondence: Enanta Pharmaceuticals, INC.; Attn: Patent DEPT.; 500 Arsenal Street; Watertown; MA; 02472; US Patent Application Number: 20040002464 Date filed: June 25, 2002 Abstract: There are described 11-C-substituted derivatives of erythromycin and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described is a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeuticallyeffective amount of a compound of the invention, and processes for the preparation of such compounds. Excerpt(s): This application is related to commonly assigned United States patent application, serial no. (Attorney Docket No. ENP041), filed on even date herewith. The present invention relates to novel macrolides having antibacterial activity and useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to a novel class of 11-C-substituted erythromycin derivatives, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. The search for macrolides active against MLS.sub.B-resistant strains (MLS.sub.B=Macrolides-Lincosamides-type B Streptogramines) has become a major goal, together with retaining the overall profile of the macrolides in terms of stability, tolerance and pharmacokinetics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
9-amino erythromycin derivatives with antibacterial activity Inventor(s): Djuric, Stevan; (Libertyville, IL), Ma, Zhenkun; (Gurnee, IL), Phan, Ly Tam; (Park City, IL), Zhang, Suoming; (Branford, CT) Correspondence: Steven F. Weinstock; Abbott Laboratories; D-377 / Ap6d-2; 100 Abbott Park Road; Abbott Park; IL; 60064-6050; US Patent Application Number: 20020132782 Date filed: January 18, 2001 Abstract: Compounds of formula (I) 1and formula (II) 2or therapeutically acceptable salts or prodrugs thereof are useful as antibacterial agents. Methods to make the compounds, compositions containing the compounds, and methods of treatment using the compounds are also disclosed.
10
This has been a common practice outside the United States prior to December 2000.
Patents 105
Excerpt(s): The present invention relates to 9-amino erythromycin derivatives which are antibacterial agents, compositions containing the compounds, methods for making the compounds, synthetic intermediates employed in the processes, and methods for the treatment of bacterial infections. Macrolide antibacterial agents are widely used to treat and prevent bacterial infections. However, the discovery of bacterial strains having resistance or insufficient susceptibility to macrolide antibacterial agents has spurred the development of compounds with modified or improved profiles of antibiotic activity. One such class of compounds are 9-amino erythromycin derivatives. 9-Amino erythromycin derivatives are macrolide antibacterial agents with a core ring structurally similar to the erythronolide A or B ring except for the presence of a substituted or unsubstituted nitrogen moiety at the 9-position. U.S. Pat. No. 6,025,350 discloses the preparation of C-4"-substituted 9-amino erythromycin derivatives. PCT application WO 99/21866, published May 6, 1999 discloses 9-aminoketolides. The clinical application of macrolide antibiotics such as erythromycin is limited, due in part to their instability at lower pH, that is, low acid stability. Under acidic conditions, such as, for example, in the gut, intramolecular cyclization occurs as the 6-hydroxyl attacks the 9-keto group, leading to intermediates which lack significant antibacterial activity (J. Majer, Antimicrob. Agents Chemother., 19, 628-633 (1981); K. Tsuji, J. Chrom., 158, 337-348 (1978); G. S. Duthu, J. Liq. Chrom., 7, 1023-1032 (1984)). The presence of the amino group at the 9-position would improve acid stability in this novel series of compounds. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Acne treating composition Inventor(s): Balaji, Kodumudi S.; (Lansdale, PA), Dorrell, Jay; (Vicksburg, MI), Mahoney, Linda M.; (Phoenixville, PA), Manetta, Vincent E.; (Bordentown, NJ), Nordsiek, Michael T.; (Berwyn, PA) Correspondence: H Eric Fischer; Synnestvedt & Lechner; 2600 Aramark Tower; 1101 Market Street; Philadelphia; PA; 19107-2950; US Patent Application Number: 20030044432 Date filed: August 21, 2002 Abstract: A package comprising components which, upon being mixed, are capable of forming a pharmaceutical composition that is effective in treating acne, the composition tending to degrade prematurely, one of the components comprising an oxidizing agent and another of the components comprising an antibiotic which is effective against acneassociated bacterial species, the components separated one from the other in the package, one component having a viscosity within about 50% of the viscosity of the other component. In addition, a package comprising: (A) components which, upon being mixed, are capable of forming a pharmaceutical composition that is effective in treating acne, one of the components comprising a benzoyl peroxide gel and another of the components comprising a gel of erythromycin and hydroxypropylcellulose; and (B) containers for holding the components in the package separated one from the other; the components having viscosities such that, upon the application of a uniform forces to the components, substantially equal volumes of the components are capable of being dispensed simultaneously from the containers. Excerpt(s): The present invention relates to a pharmaceutical composition that tends to lose its effectiveness prematurely and to improved means for the effective use of such a composition. More particularly, the present invention relates to the packaging of constituents comprising such a composition and to an improved form of such
106
Erythromycin
composition, including, for example, a composition for topical application, such as a topical composition for the treatment of acne. Acne is a common inflammatory disease which is very common at puberty and may continue for many years. It occurs in facial skin areas where sebaceous glands are the largest, most numerous, and most active. In its milder forms, acne is a superficial disorder which is evidenced by slight, spotty irritations and which can be treated satisfactorily by ordinary skin hygiene. However, in the more inflammatory types of acne, bacterial invasion of or about the pilosebaceous follicles occurs and results in the formation of pustules, infected cysts, and, in extreme cases, canalizing inflamed and infected sacs appear. These lesions may become extensive and leave permanent, disfiguring scars. Therapeutic methods for treating acne are designed to prevent formation of new lesions and facilitate the healing of old lesions. Treatments include the systemic and topical administration of anti-acne agents such as antibiotics or synthetic Vitamin A analogs. In most cases, systemic treatment of acne is not desirable because of the risks of adverse side effects that are experienced by the user. For this reason, topical acne treatment compositions have been preferred. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Amphiphilic oligomers Inventor(s): Ekwuribe, Nnochiri Nkem; (Cary, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20030229006 Date filed: May 30, 2003 Abstract: A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Didesoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications. Excerpt(s): The present invention relates to microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents, and to methods of making and using same. The compositions of the invention may comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents,
Patents 107
antibiotics, antiarrhymics, anti-coagulants, etc., and prodrugs, precursors, derivatives, and intermediates thereof. In the field of pharmaceutical therapeutic intervention, and the treatment of disease states and physiological conditions, a wide variety of therapeutic agents have come into use, including various proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhythmics, anti-coagulants, etc., and prodrugs precursors, derivatives, and intermediates of the foregoing. For example, the use of polypeptides and proteins for the systemic treatment of specific diseases is now well accepted in medical practice. The role that the peptides play in replacement therapy is so important that many research activities are being directed towards the synthesis of large quantities by recombinant DNA technology. Many of these polypeptides are endogenous molecules which are very potent and specific in eliciting their biological actions. Other non-(poly)peptidyl therapeutic agents are equally important and pharmaceutically efficacious. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antibiotics for treating biohazardous bacterial agents Inventor(s): Cassell, Gail Houston; (Carmel, IN), Nicas, Thalia Ioanna; (Indianapolis, IN) Correspondence: Eli Lilly And Company; Patent Division; P.O. Box 6288; Indianapolis; IN; 46206-6288; US Patent Application Number: 20030176327 Date filed: October 18, 2002 Abstract: The present invention is directed to methods for the control of strains of biohazardous bacterial agents. These agents include: Bacillus anthracis, Yersinia Pestis, Francisella tularensis, Clostridium botulinin, Clostridium Perfringens, Brucella abortis, B milletensis, B suis and Burkholderia mallei. These methods employ treating an infected warm-blooded animal with an antibiotics selected from: Cephalothin, Cefazolin, Cephalexin monohydrate, Cephalexin HCl, Cefaclor, Loracarbef, Erythromycin estolate, Dirithromycin, Cinoxacin, Vancomycin HCl, Tobramycin, Cefamandole, Cefuroxime, Daptomycin, and Oritavancin. Excerpt(s): Of the numerous bio-hazardous bacterial agents that may be used as weapons, there are a limited number of organisms that could cause disease and deaths in sufficient numbers to cripple a city or region. These organisms include: Bacillus anthracis, Yersinia Pestis, Francisella tularensis, Clostridium botulinin, Clostridium, Perfringens, Brucella abortis, B milletensis, B suis and Burkholderia mallei. Anthrax, attributable to infection with Bacillus anthracis, is among the most serious diseases that can be contracted from a bio-hazardous agent. Biological agents have seldom been dispersed in aerosol form, the exposure mode most likely to inflict widespread disease. Therefore, historical experience provides little information about the potential impact of a biological attack or the possible efficacy of postattack measures such as vaccination, antibiotic therapy, or quarantine. For centuries, anthrax has caused disease in animals and, uncommonly, serious illness in humans throughout the world. (see D. Lew , Bacillus anthracis (anthrax); in G. L. Mandell, J. E. Bennett, R. Dolin, eds.; Principles and Practices of Infectious Disease, New York, N.Y.; Churchill Livingstone Inc; 1885-1889 (1989)). Research on anthrax as a biological weapon began more than 80 years ago. (see G. W. Christopher, T. J. Cieslak, J. A. Pavlin, and E. M. Eitzen, "Biological warfare: a historical perspective," JAMA 278, 412-417 (1997)). Today, at least 17 nations are believed to have offensive biological weapons programs (see L. A. Cole, "The specter of biological weapons," Sci.Am., 60-65 (December 1996)); it is uncertain how many are
108
Erythromycin
working with anthrax. Iraq has acknowledged producing and weaponizing anthrax. (see R. A. Zalinskas, "Iraq's biological weapons: the past as future?," JAMA 278, 418-424 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Arylation method for the functionalization of O-allyl erythromycin derivatives Inventor(s): Haight, Anthony R.; (Wadsworth, IL), Hsu, Margaret Chi-Ping; (Vernon Hills, IL), Narayanan, Bikshandarkoil A.; (Mundelein, IL), Peterson, Matthew John; (Redwood City, CA), Zhang, Weijang; (Grayslake, IL) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20030125531 Date filed: May 28, 2002 Abstract: An efficient arylation technique for use in the synthesis of erythromycin derivatives, involving a modified Heck reaction which employs less than six mole percent of palladium catalyst and no phosphine is disclosed. With this modified Heck reaction, an O-alkenylaryl macrolide can be obtained in a much shorter reaction time than under conventional Heck reaction conditions. The modified Heck reaction can be utilized in a method for phosphine-free arylation of an O-allylic erythromycin derivative, in a method for preparing an O-alkenylaryl erythromycin A derivative, or in a method for preparing a 2',4"-hydroxyl protected 6-O-alkenylaryl erythromycin A derivative. Excerpt(s): This application claims priority from Provisional Application No. 60/294,326, filed May 30, 2001. The present invention is directed to an efficient arylation technique for use in the synthesis of erythromycin derivatives, involving a modified Heck reaction which employs less than six mole percent of palladium catalyst and no phosphine. With this modified Heck reaction, an O-alkenylaryl macrolide can be obtained in a much shorter reaction time than under conventional Heck reaction conditions. The modified Heck reaction can be utilized in a method for phosphine-free arylation of an O-allylic erythromycin derivative, in a method for preparing an Oalkenylaryl erythromycin A derivative, or in a method for preparing a 2',4"-hydroxyl protected 6-O-alkenylaryl erythromycin A derivative. Erythromycins A through D, represented by Formula I and Table 1 shown below, are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
C12 Modified erythromycin macrolides and ketolides having antibacterial activity Inventor(s): Burger, Matthew; (Albany, CA), Carroll, Georgia Law; (Walnut Creek, CA), Chu, Daniel; (Santa Clara, CA), Lin, Xiaodong; (Walnut Creek, CA), Plattner, Jacob; (Berkeley, CA), Rico, Alice; (Berkeley, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030125266 Date filed: July 3, 2002
Patents 109
Abstract: Antimicrobial macrolide compounds are provided having formulas II: 1as well as pharmaceutically acceptable salts, esters or prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/302,825 filed Jul. 3, 2001. This invention relates to novel semi-synthetic macrolides and ketolides having antibacterial activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treatment. More particularly, this invention concerns to C12 modified erythromycin macrolides and ketolide derivatives, compositions containing these compounds, methods of producing the compounds and methods of treating bacterial infections. are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection. As with other antibacterial agents, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore, there is a continuing need to identify new erythromycin derivative compounds which possess improved antibacterial activity, which have less potential for developing resistance, which possess Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Consequently, numerous investigators have prepared chemical derivatives of erythromycin in an attempt to obtain analogs having modified or improved profiles of antibiotic activity. For example, the compound 6-OMe erythromycin A, or clarithromycin, has found widespread use. However, even this compound is beginning to lose its effectiveness and other erythromycin derivatives having improved activity are needed. Other 6-O-substituted erythromycin compounds have also been proposed for this purpose. For example, PCT application WO 92/09614, published Jun. 11, 1992, discloses tricyclic 6-O-methylerythromycin A derivatives. U.S. Pat. No. 5,444,051 discloses 6-O-substituted-3-oxoerythromycin A derivatives in which the substituents are selected from alkyl, ----CONH.sub.2, ----CONHC(O)alkyl and ----CONHSO.sub.2 alkyl. PCT application WO 97/10251, published Mar. 20, 1997, discloses 6-O-methyl 3descladinose erythromycin derivatives. European Patent Application 596802, published May 11, 1994, discloses bicyclic 6-O-methyl-3-oxoerythromycin A derivatives. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Derivatives of erythromycin, their preparation process and their use as medicaments Inventor(s): Denis, Alexis; (Paris, FR) Correspondence: Charles A. Muserlian; C/o Bierman, Muserlian And Lucas; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030050254 Date filed: July 2, 2002 Abstract: A subject of the invention is the compounds of formula 1in which Y represents a hydrogen atom or a fluorine atom, n represents an integer comprised between 1 and 8, Z represents a hydrogen atom or the remainder of a carboxylic acid,optionally substituted on the heterocycle by one or more alkyl, alkenyl, alkynyl, 0-alkyl, O-alkenyl, 0-alkynyl, S-alkyl, S-alkenyl, S-alkynyl radicals containing up to 8 carbon atoms, one or more OH, NH.sub.2, C=N, NO.sub.2, CF.sub.3 radicals or one or more aryl radicals containing up to 14 carbon atoms or heteroaryl radicals containing one or more nitrogen oxygen or sulphur atoms, the aryl or heteroaryl radicals themselves being able to be
110
Erythromycin
substituted as well as their addition salts with acids,The products of formula (I) have antibiotic properties. Excerpt(s): The present invention relates to new derivatives of erythromycin, their preparation process and their use as medicaments. optionally substituted on the heterocyle by one or more alkyl, alkenyl, alkynyl, 0-alkyl, 0-alkenyl, 0-alkynyl, S- alkyl, S-alkenyl, S-alkynyl radicals containing up to 8 carbon atoms, one or more OH, NH.sub.2, C=N, N0.sub.2, CF.sub.3 radicals or one or more aryl radicals containing up to 14 carbon atoms or heteroaryl radicals containing one or more nitrogen oxygen or sulphur atoms, the aryl or heteroaryl radicals themselves being able to be substituted as well as their addition salts with acids. As an example of the addition salts of the present derivatives with mineral or organic acids, the salts formed with acetic, propionic, trifluoroacetic, maleic, tartaric, methanesulphonic, benzenesulphonic, ptoluenesulphonic, hydrochloric, hydrobromic, hydroiodic, sulphuric, phosphoric acids and especially stearic, ethylsuccinic or laurylsulphonic acids can be mentioned. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Erythromycin derivative having novel crystal structures and processes for their production Inventor(s): Hiraide, Akira; (Tokyo, JP), Koyama, Kaichiro; (Tokyo, JP), Shimizu, Hitoshi; (Tokyo, JP), Tsuzaki, Kaname; (Tokyo, JP) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20030191296 Date filed: April 14, 2003 Abstract: The present invention provides an E-type crystal of N-demethyl-N-isopropyl12-methoxy-11-oxo-8,9-anhydroerythromycin A-6,9-hemiacetal fumarate having strong diffraction peaks at diffraction angles (2.theta.) of 5.6.degree. and 10.4.degree. as measured by powder X-ray diffractometry, which is prepared by treating a C-type crystal of the compound in a mixed solvent of ethyl acetate and water at 20.degree. C. to 40.degree. C., and a D-type crystal prepared via the E-type crystal. These crystals have a reduced content of residual solvent and high suitability for formulation. Excerpt(s): The present invention relates to novel crystals of fumarate salts of erythromycin derivatives and a method for their preparation. is disclosed in, for example, JP 6-56873 A (WO93/24509) and JP 9-100291 A (WO97/06177). This compound is known to have the ability to enhance the movement of the digestive tract. The preparation of this compound is disclosed in, for example, JP 9-100291 A, Bioorg. & Med. Chem. Lett. vol. 4(11), 1347 (1994) and JP 9-100291 A. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 111
•
Extended release formulations of erythromycin derivatives Inventor(s): Devcich, Karen J.; (Grayslake, IL), Hom, Richard C.; (Wilmette, IL), Notario, Gerard F.; (Chicago, IL), Palmer, Robert N.; (Gurnee, IL), Semla, Susan J.; (Evanston, IL), Zhang, Jie; (Basking Ridge, NJ) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20030133981 Date filed: November 22, 2002 Abstract: Disclosed is a pharmaceutical composition for extended release of an erythromycin derivative in the gastrointestinal environment. The composition comprises an erythromycin derivative and a pharmaceutically acceptable polymer so that, when ingested orally, the composition induces statistically significantly lower C.sub.max in the plasma than an immediate release composition of the erythromycin derivative while maintaining bioavailability and minimum concentration substantially equivalent to that of the immediate release composition of the erythromycin derivative upon multiple dosing. The compositions of the invention have an improved taste profile and reduced gastrointestinal side effects as compared to those for the immediate release composition. Excerpt(s): The present application is a continuation-in-part of U.S. patent application Ser. No. 08/838,900, filed Apr. 11, 1997, now allowed. The present invention relates to pharmaceutical compositions of erythromycin derivatives with an extended release of an active compound in the gastrointestinal environment. More particularly, it relates to pharmaceutical compositions of clarithromycin which are ingested daily as a single oral administration. Erythromycin and its derivatives are known for their antibacterial activity against a number of organisms or activity in a number of indications and are typically administered as immediate release (IR) compositions, two or three times a day, for a regimen of 10 to 14 days. These compounds have a bitter taste. In particular, the 6O-methoxyerythromycin A (clarithromycin) has a bitter metallic taste which can result in poor compliance of the regimen or selection of another, possibly less effective, therapeutic agent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Inhibition of human immunodeficiency virus reverse transcriptase Inventor(s): Hung, Paul Porwen; (Bryn Mawr, PA) Correspondence: Y. Rocky Tsao; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020187944 Date filed: March 21, 2002 Abstract: A method of inhibiting a human immunodeficiency virus reverse transcriptase by contacting the reverse transcriptase with an effective amount of 9-O-methyl oxime erythromycin A. Excerpt(s): This application claims priority from U.S. Provisional Patent Application Serial No. 60/277,583, filed Mar. 21, 2001. Human immunodeficiency virus (HIV) has proven to be an intractable pathogen. One strategy has been to target the reverse transcriptase of this virus. The invention is based on the unexpected discovery that 9-O-
112
Erythromycin
methyl oxime erythromycin A inhibits HIV reverse transcriptase and thereby blocks HIV replication at low concentrations, as compared with previous studies on other retroviruses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Library of novel ''unnatural'' natural products Inventor(s): McDaniel, Robert; (Palo Alto, CA) Correspondence: Brenda J. Wallach, PH.D.; Morrison & Foerster Llp; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130-2332; US Patent Application Number: 20030138841 Date filed: April 22, 2002 Abstract: Genetic engineering of the erythromycin polyketide synthase genes to effect combinatorial alterations of catalytic activities in the biosynthetic pathway can be used to generate a library of macrolides impractical to produce by chemical methods. The library includes examples of analogs with one, two and three altered carbon centers of the polyketide products. Excerpt(s): This application claims priority to and is a continuation of U.S. Ser. No. 09/429,349, filed Oct. 28, 1999, which is a continuation-in-part of U.S. Ser. No. 09/073,538, filed May 6, 1998, which is a continuation-in-part of U.S. Ser. No. 08/846,247, filed Apr. 30, 1997. This application also claims priority to U.S. provisional application Ser. Nos. 60/076,919, filed Mar. 5, 1998, and 60/105,987, filed Oct. 28, 1998, and PCT application No. US98/08792, filed Apr. 30, 1998. Each of the above patent applications is incorporated herein by reference. The present invention provides recombinant DNA compounds and host cells containing novel polyketide synthase (PKS) genes and novel polyketides. The invention relates to the fields of chemistry, medicinal chemistry, human and veterinary medicine, molecular biology, pharmacology, agriculture, and animal husbandry. Few molecules have captured interest in both chemotherapy and chemistry to the extent of the polyketide erythromycin and its semi-synthetic derivatives. Erythromycin and its congeners are the third most widely used class of antibiotics, with current worldwide sales exceeding US $3.5 billion. In addition, erythromycin analogs are gaining interest for their potential use in the treatment of gastrointestinal disorders (Omura, "The expanded horizon for microbial metabolites--a review," Gene 115, 141-149 (1992)), inflammatory diseases (Kawasaki et al., "Roxithromycin inhibits cytokine production by and neutrophil attachment to human bronchial epithelial cells in vitro," Antimicrob. Agents Chemother. 42, 1499-1502 (1998)), and as next-generation antibiotics for treatment of emerging drugresistant strains of bacteria (Agoudiras et al., "In-vitro antibacterial activity of RU 004 (HMR 3004), a novel ketolide derivative active against respiratory pathogens," Antimicrob. Agents Chemother. 41, 2149-2158 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 113
•
Method and apparatus for separating a component from a mixture Inventor(s): Farrenburg, Chad; (Sikeston, MO), Hritzko, Benjamin J.; (Groton, CT), Wang, Nien-Hwa Linda; (West Lafayette, IN), Xie, Yi; (West Lafayette, IN) Correspondence: Intellectual Property Group; Bose Mckinney & Evans Llp; 2700 First Indiana Plaza; 135 North Pennsylvania Street; Indianapolis; IN; 46204; US Patent Application Number: 20030229213 Date filed: May 31, 2002 Abstract: The present invention comprises the optimization of a four zone simulated moving bed system configured to separate a first component from a mixture containing the first component and a second component wherein the first component exhibits nonlinear adsorption and non-negligible mass transfer resistances. In one example, the four zone simulated moving bed is optimized to separate Clarithromycin from a mixture containing Clarithromycin and 6,11-O-methyl erythromycin A. The present invention further comprises a four zone or a five zone apparatus having a first portion and a second portion and the optimization of the four zone or five zone apparatus to separate a first component from a mixture containing the first component and a second component and the method of using the same. In one example, the four zone and five zone simulated moving beds are optimized to separate Clarithromycin from a mixture containing Clarithromycin and 6,11-O-methyl erythromycin A. The present invention further comprises a batch elution system configured to separate Clarithromycin from a mixture containing Clarithromycin and 6,11-O-methyl erythromycin A. Excerpt(s): The present invention relates to methods for separating a component from a mixture, in particular for separating a component from a mixture wherein the component and at least one other component of the mixture have similar chemical structures or adsorption properties, such as separating from a mixture a first component of 6-O-methyl erythromycin A (Clarithromycin) from a second component of 6,11-Omethyl erythromycin A. One method of separating chemical compounds is chromatography wherein the compounds are separated based upon their different adsorption properties. However, chemical compounds, which have similar chemical structures, are difficult to separate with chromatography due to their similar properties such as adsorption. One example of this is exhibited in the difficulty in purifying a viable product, 6-O-methyl erythromycin A (Clarithromycin) from the impurity, 6,11-Omethyl erythromycin A. Clarithromycin is an effective antibiotic obtained by the chemical methylation of erythromycin, a naturally occurring antibiotic. The mixture of Clarithromycin and 6,11 may be recovered in a nearly one-to-one solid mixture of Clarithromycin and 6,11. This solid mixture may contain up to 23% other impurities. These additional impurities are easily separated from Clarithromycin by crystallization. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Methods and apparatus for adhering musculoskeletal tissues Inventor(s): Ferree, Bret A.; (Cincinnati, OH) Correspondence: John G. Posa; Gifford, Krass, Groh, Sprinkle,; Anderson & Citkowski, P.C.; Suite 400, 280 N. Old Woodward AVE.; Birmingham; MI; 48009-5394; US Patent Application Number: 20030192554 Date filed: April 11, 2003
114
Erythromycin
Abstract: A method of adhering musculoskeletal tissues such as tendons, ligaments, and cartilage involves applying one or more substances to enhance adhesion. According to one aspect, scar-forming substances are applied to the tissues that the surgeon wishes to connect. For example, tetracycline, nitrogen mustard, sterile talcum powder, erythromycin, or alternative substances may be applied to the tissues. A second aspect of the invention uses growth factors such as those found in platelet-rich plasma (PRP) to accelerate the healing. The growth factors could be sprayed onto the tissues the surgeon wishes to connect. A third aspect uses "glue" such as "fibrin glue" to bond the tissues together. Regardless of the embodiment, an inventive retractable catheter may be used to administer the agent(s) so as not to expose unintended areas. Excerpt(s): This application claims priority from U.S. Provisional Patent Application Serial No. 60/371,903, filed Apr. 11, 2002, the entire content of which is incorporated herein by reference. This invention relates generally to spinal surgery and, in particular, for adhering musculoskeletal tissues. According to current practice, musculoskeletal tissues such as tendons, ligaments, and cartilage are connected surgically with sutures and staples. Generally, the synthetic staples and sutures provide provisional fixation. Long-term connection of the tissues is dependent upon the tissues healing together, however. The natural healing process relies on the formation of fibrous scar tissue between the surgically connected tissues. In a sense, there is a race between failure of the suture and the formation of scar tissue with sufficient tensile strength to hold the tissues together. At times a patient's anatomy can make suturing or stapling of tissues difficult. For example, a surgeon may wish to connect two or more tissues inside a structure such as the intervertebral disc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods utilizing aryl thioimines in synthesis of erythromycin derivatives Inventor(s): Lukin, Kirill A.; (Mundelein, IL) Correspondence: Steven F. Weinstock; Abbott Laboratories; D-377/ap6d; 100 Abbott Park Road; Abbott Park; IL; 60064-6050; US Patent Application Number: 20020115835 Date filed: December 21, 2000 Abstract: An efficient deoximation technique for use in synthesis of erythromycin derivatives, involving aryl thioimine intermediates is disclosed. The aryl thioimine intermediates can be utilized in a method for protecting a ketone of a ketone-containing erythromycin derivative as a thioimine; a method for deoximating an oxime-containing erythromycin derivative, or a method for preparing a 6-O-alkyl erythromycin derivative. Presently preferred erythromycin derivatives have a C-9 oxime or a C-9 ketone. Excerpt(s): The present invention is directed to an efficient deoximation technique for use in the synthesis of erythromycin derivatives, involving aryl thioimine intermediates. The aryl thioimine intermediates can be utilized in a method for protecting a ketone of a ketone-containing erythromycin derivative as a thioimine; a method for deoximating an oxime-containing erythromycin derivative, or a method for preparing a 6-O-alkyl erythromycin derivative. Presently preferred erythromycin derivatives have a C-9 oxime or a C-9 ketone. As with other anti-bacterial agents, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore,
Patents 115
there is a continuing need to identify and synthesize new erythromycin derivative compounds which possess improved anti-bacterial activity, which have lower potential for developed resistance, which possess the desired Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Generally, 6-O-alkyl derivatives of erythromycin are known as anti-bacterial agents. 6-O-methyl erythromycin A (clarithromycin A, disclosed in U.S. Pat. No. 4,331,803) and 6-O-methyl erythromycin B (clarithromycin B, disclosed in U.S. Pat. No. 4,496,717) are potent macrolide antibiotics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
MODIFIED MODULAR PKS WITH RETAINED SCAFFOLD Inventor(s): ASHLEY, GARY; (ALAMEDA, CA), FU, HONG; (STANFORD, CA), KAO, CAMILLA M.; (STANFORD, CA), KHOSLA, CHAITAN; (STANFORD, CA), MCDANIEL, ROBERT; (PALO ALTO, CA) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20020034797 Date filed: April 30, 1997 Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 08/486,645 filed Jun. 7, 1995 which is continuation-in-part of U.S. Ser. No. 08/238,811 filed May 6, 1994. The disclosures of these applications are incorporated herein by reference. The invention relates to the field of combinatorial libraries. More particularly, it concerns construction of libraries of polyketides synthesized by a multiplicity of polyketide synthases derived from a naturally occurring PKS, as illustrated by the erythromycin gene cluster. Polyketides represent a large family of diverse compounds ultimately synthesized from 2-carbon units through a series of Claisen-type condensations and subsequent modifications. Members of this group include antibiotics such as tetracyclines, anticancer agents such as daunomycin, and immunosuppressants such as FK506 and rapamycin. Polyketides occur in many types of organisms including fungi and mycelial bacteria, in particular, the actinomycetes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
New derivatives of erythromycin, their preparation process and their use as medicaments Inventor(s): Agouridas, Constantin; (Nogent Sur Marne, FR), Denis, Alexis; (Paris, FR), Fromentin, Claude; (Paris, FR) Correspondence: Charles A. Muserlian; C/o Bierman, Muserlian And Lucas; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20020028781 Date filed: December 11, 2000
116
Erythromycin
Abstract: A subject of the invention is, as new chemical products, the compounds of formula (I) 1in which X represents a hydrogen atom or a halogen atom and Z represents a hydrogen atom or the remainder of an acid as well as their addition salts with acids.The compounds of formula (I) have antibiotic properties. Excerpt(s): The present invention relates to new derivatives of eryrthromycin, their preparation process and their use as medicaments. in which X represents a hydrogen atom or a halogen atom and Z represents a hydrogen atom or the remainder of an acid as well as their addition salts with acids. Among the addition salts with acids, the salts formed with acetic, propionic, trifluoroacetic, maleic, tartaric, methanesulphonic, benzenesulphonic, p-toluenesulphonic acids and particularly stearic, ethylsuccinic or laurylsulphonic acids, can be mentioned. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel cyclohexene derivatives useful as antagonists of the motilin receptor Inventor(s): Chen, Robert H.; (Belle Mead, NJ), Xiang, Min A; (Bridgewater, NJ) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20020002192 Date filed: March 9, 2001 Abstract: The compounds of formula I are useful in treating gastrointestinal disorders associated with antagonizing the motilin receptor. The compounds compete with erythromycin and motilin for the motilin receptor. In addition the compounds are antagonists of the contractile smooth muscle response to those ligands. Excerpt(s): This invention relates to a series of novel cyclohexene derivatives, pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention are useful as non-peptidyl antagonists of the motilin receptor. In mammals, the digestion of nutrients and the elimination of waste is controlled by the gastrointestinal system. This system is, to say the least, complicated. There are a number of natural peptides, ligands, enzymes, and receptors which play a vital role in this system and are potential targets for drug discovery. Modifying the production of, or responses to these endogenous substances can have an effect upon the physiological responses such as diarrhea, nausea, and abdominal cramping. One example of an endogenous substance which affects the gastrointestinal system is motilin. Motilin is a peptide of 22 amino acids which is produced in the gastrointestinal system of a number of species. Although the sequence of the peptide varies from species to species, there are a great deal of similarities. For example, human motilin and porcine motilin are identical; while motilin isolated from the dog and the rabbit differ by five and four amino acids, respectively. Motilin induces smooth muscle contractions in the stomach tissue of dogs, rabbits, and humans as well as in the colon of rabbits. Apart from local gastrointestinal intestinal tissues, motilin and its receptors have been found in other tissues. For example, motilin has been found in circulating plasma, where a rise in the concentration of motilin has been associated with gastric effects which occur during fasting in dogs and humans (Itoh, Z. et al., 1976, Scand. J. Gastroenterol. 11:93-110; Vantrappen, G. et al., 1979, Dig. Dis Sci 24, 497-500). In addition, when motilin was intravenously administered to humans it was found to increase gastric emptying and gut hormone release (Christofides, N. D. et al., 1979, Gastroenterology 76:903-907).
Patents 117
Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel polyketide derivatives and recombinant methods for making same Inventor(s): Kakavas, Stephan J.; (Buffalo Grove, IL), Katz, Leonard; (Wheeling, IL), Pereda-Lopez, Ana; (Mundelein, IL), Ruan, Xiaoan; (Lake Bluff, IL), Stassi, Diane L.; (Highland Park, IL), Summers, Richard G. JR.; (Nashotah, WI) Correspondence: Steven F. Weinstock; Abbott Laboratories; Department 377 / Ap6d-2; 100 Abbott Park Road; Abbott Park; IL; 60064-6050; US Patent Application Number: 20030013662 Date filed: December 11, 2000 Abstract: The invention provides novel erythromycin derivatives in which methyl groups on the macrolactone ring have been substituted with --H, -Et, and/or --OH. The invention also provides reagents such as isolated polynucleotides, vectors comprising the polynucleotides and host cells transformed with the vectors for making the novel compounds. Methods for making the compounds utilizing genetic engineering techniques are also disclosed. Excerpt(s): This application is a continuation-in-part of co-pending U.S. application Ser. No. 07/642,734, filed Jan. 17, 1991. The present invention relates to novel polynucleotide sequences, proteins encoded therefrom which are involved in the biosynthesis of polyketides, methods for directing the biosynthesis of novel polyketides using those polynucleotide sequences and novel derivatives produced therefrom. In particular, the invention relates to the production of novel polyketide derivatives through manipulation of the genes encoding polyketide synthases. Polyketides are a large class of natural products that includes many important antibiotic, antifungal, anticancer, antihelminthic, and immunosuppressant compounds such as erythromycins, tetracyclines, amphotericins, daunorubicins, avermectins, and rapamycins. Their synthesis proceeds by an ordered condensation of acyl esters to generate carbon chains of varying length and substitution pattern that are later converted to mature polyketides. This process has long been recognized as resembling fatty acid biosynthesis, but with important differences. Unlike a fatty acid synthase, a typical polyketide synthase is programmed to make many choices during carbon chain assembly: for example, the choice of "starter" and "extender" units, which are often selected from acetate, propionate or butyrate residues in a defined sequence by the polyketide synthase. The choice of using a full cycle of reduction-dehydration-reduction after some condensation steps, omitting it completely, or using one of two incomplete cycles (reduction alone or reduction followed by dehydration) is additionally programmed, and determines the pattern of keto or hydroxyl groups and the degree of saturation at different points in the chain. Finally, the stereochemistry for the substituents at many of the carbon atoms is programmed by the polyketide synthase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
118
•
Erythromycin
Novel tricyclic erythromycin derivatives Inventor(s): Wu, Yong-Jin; (Madison, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020061856 Date filed: April 24, 2000 Abstract: The present invention relates to compounds of the formula 1and to pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.6 and R.sup.7 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1, methods of using said compounds of formula 1 in the treatment of bacterial and protozoa infections, and methods of preparing said compounds of formula 1. Excerpt(s): This invention relates to novel tricyclic erythromycin derivatives. The compounds of this invention are useful as antibiotic agents in mammals, including man, as well as in fish and birds. The compounds of the present invention are broad-spectrum macrolide antibiotics that are effective against infections caused by certain grampositive and gram-negative bacteria as well as protozoa. Various derivatives of erythromycin A that are useful as antibiotic agents are referred to in U.S. patent application Ser. No. 60/049,349, filed Jun. 11, 1997; U.S. application Ser. No. 60/046,150, filed May 9, 1997; U.S. patent application Ser. No. 60/063,676, filed Oct. 29, 1997; U.S. patent application Ser. No. 60/087,798, filed Jun. 3, 1998; U.S. application Ser. No. 60/054866, filed Aug. 6, 1997; U.S. patent application Ser. No. 60/063,161, filed Oct. 29, 1997; U.S. patent application Ser. No. 60/117,342, filed Jan. 27, 1999; U.S. patent application Ser. No. 60/130,809, filed Apr. 23, 1999; U.S. patent application Ser. No. 60/130,912, filed Apr. 23, 1999; U.S. patent application Ser. No. 60/130,913, filed Apr. 23, 1999; each of the foregoing U.S. patent applications is incorporated herein by reference in its entirety. each Z is independently a 4 to 10 membered heterocyclic group or C.sub.6-C.sub.10 aryl, wherein said heterocyclic and aryl groups are optionally substituted by 1 to 5 R.sup.13 substituents. More specific embodiments of this invention include compounds of formula 1 wherein R.sup.5 is methyl, ethyl, n-propyl, or CH.sub.2-CH=CH-Z. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Process for producing erythromycin derivative Inventor(s): Adachi, Takashi; (Tokyo, JP), Kamiyama, Hiroaki; (Tokyo, JP), Kashimura, Masato; (Tokyo, JP), Kuwada, Takeshi; (Tokyo, JP), Suzuki, Nobuyuki; (Tokyo, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030191295 Date filed: February 12, 2003 Abstract: There is provided a preparation process useful for an efficient synthesis of 6O-substituted ketolide derivatives by combining a characterized step of introduction of a substituent at the 6-position by selective cleavage of a C--O bond of the cyclic acetal at the 9-position side via 6,9-cyclic acetal 5-O-desosaminyl erythronolide derivative, a step
Patents 119
of conversion into carbonyl groups at the 9- and 3-positions, and a step of 11,12-cyclic carbamation to lead to 6-O-substituted ketolide derivatives. Excerpt(s): The present invention relates to processes for preparing erythromycin derivatives and to intermediates thereof, and particularly relates to a process for preparing 6-O-substituted ketolide derivatives starting from erythromycin and to intermediates thereof. Macrolide antibiotics including erythromycin A have a strong antibacterial activity against Gram-positive bacteria, some Gram-negative bacteria, Mycoplasmas and the like, and have been widely used as agents for the treatment of infections caused by these bacteria. Furthermore, many erythromycin derivatives have been synthesized for the purpose of the improvement of pharmacokinetic properties of erythromycin A, and some of them have already been clinically used as excellent antibiotics. For example, clarithromycin (6-O-methylerythromycin A, U.S. Pat. No. 4,331,803) has been widely used as a therapeutic agent of respiratory tract infections due to its excellent biological properties. There has been recently reported the derivatives which are generically called ketolides and have a potent antibacterial activity against macrolide-resistant bacteria. The structural features of these derivatives are such that the cladinose group at the 3-position of erythromycin A has been removed, and converted into a carbonyl group, the hydroxyl group at the 6-position has been alkylated, and the hydroxyl groups at the 11- and 12-postions have been converted into a cyclic carbamate. Among these ketolides, there is 3-deoxy-3-oxo-6-O-((3-quinol-3- -yl)prop-2-enyl)-5-Odesosaminyl erythronolide A 11,12-cyclic carbamate (U.S. Pat. No. 5,866,549, and J. Medicinal Chemistry, vol. 43, pp.1045-1049 (2000)), which has a strong antibacterial activity against both of macrolide-sensitive and macrolide-resistant bacteria that cause respiratory tract infections. As mentioned above, this compound is prepared by modifying at three positions, i.e., at the 6-, 3- and 11,12-positions. The preparation process reported is carried out by once converting the carbonyl group at the 9-position into an oxime derivative, modifying at the 6-position and reproducing a carbonyl group at the 9-position, therefore this manufacturing process needs many steps, and is complicated. An object of the present invention is to provide processes for preparing erythromycin derivatives and intermediates thereof, and more particularly to provide preparation processes useful for an efficient synthesis of a 6-O-substituted ketolide derivative. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for producing erythromycin derivative Inventor(s): Kurita, Mitsuhiro; (Tokyo, JP), Shimizu, Hitoshi; (Tokyo, JP), Tsuzaki, Kaname; (Tokyo, JP) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20030195343 Date filed: March 3, 2003 Abstract: A method for preparing a fumarate salt of a compound represented by Formula (II): 1(wherein R.sub.1 represents a hydrogen atom or a lower alkyl group, and R.sub.2 represents a lower alkyl group), which comprises carbamating a compound represented by Formula (I): 2(wherein R.sub.1 represents a hydrogen atom or a lower alkyl group), removing all carbamate groups from this compound, alkylating the nitrogen atom at the 3'-position of the desosamine ring in the resulting compound to give the compound represented by Formula (II), and converting this compound into a
120
Erythromycin
fumarate salt, wherein the compound represented by Formula (I) is carbamated in the presence of a cyclic ether or a carboxylic ester. This method enables efficient preparation of high-quality erythromycin derivatives. Excerpt(s): The present invention relates to a method for preparation of erythromycin derivatives. (wherein R.sub.1 represents a hydrogen atom or a lower alkyl group, and R.sub.2 represents a lower alkyl group) is described in, for example, JP 6-56873 A and JP 9-100291 A. These compounds are known to have the ability to enhance movement of the digestive tract. Methods for preparation of this compound are found in, for example, JP 6-56873 A, Bioorg. & Med. Chem. Lett., vol. 4(11), 1347 (1994) and JP 9-100291 A. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for producing purified erythromycin Inventor(s): Ishii, Megumi; (Tokyo, JP), Tsuzaki, Kaname; (Tokyo, JP) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20030120048 Date filed: September 23, 2002 Abstract: The object of the present invention is to prepare purified erythromycin by removing erythromycin F from erythromycin.The present invention provides a method for preparing purified erythromycin from which erythromycin F is removed, which comprises the step of extracting erythromycin F from erythromycin using (i) an organic solvent and (ii) water or an aqueous solution of an inorganic and/or organic material. Excerpt(s): The present invention relates to a method for preparing purified erythromycin. More specifically, the present invention relates to a method for preparing purified erythromycin, characterized by removing erythromycin F for purification. The present invention also relates to a method for preparing purified erythromycin F. More specifically, the present invention relates to a method for preparing purified erythromycin F, characterized by extracting erythromycin F for purification. Erythromycin is an antibiotic with a strong antibacterial activity against Gram-positive bacteria and the like, and is important as a pharmaceutical drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Process to obtain clarithromycin Inventor(s): Asensio Dominguez, Ramon; (Aranjuez, ES), Borrell Bilbao, Jose Ignacio; (Barcelona, ES), Cruzado Rodriguez, Maria del Carmen; (Aranjuez, ES), Diaz Tejo, Luis Angel; (Aranjuez, ES), Ribe, Rosa Nomen; (Barcelona, ES), Sempere Cebrian, Julia; (Barcelona, ES) Correspondence: Sughrue, Mion, Zinn, Macpeack & Seas Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037-3202; US Patent Application Number: 20030023053 Date filed: June 27, 2002 Abstract: This process is intended to obtain clarithromycin. According to the process, it starts from the erythromycin A 9-oxime hydrochloride, which is transformed into
Patents 121
clarithromycin by means of a synthetic sequence in which an acetal of the 9-oxime is initially formed. The use of the oxime hydrochloride permits that only the use of catalytic amounts of pyridine salts are necessary to favor the reaction. Next, the hydroxyls in positions 2' and 4" are protected with a silylating agent and the hydroxyl in position 6 is methylated; all this without the isolation of any reaction intermediate being necessary. Finally, the acetal and 2' and 4" silanes unprotection, followed by the deoximation yields clarithromycin with a high yield and a form which is easily applicable industrially. Excerpt(s): This compound was first disclosed by Y. Watanabe et al. (Taisho Pharmaceutical Co.) in the patent document EP 41.355 (and in the equivalent document U.S. Pat. No. 4,331,803). The process disclosed in said document starts from N-demethylerythromycin A and protects the 2'-hydroxyl and the de-methylamine group in the form of a benzyloxycarbonyl derivative. Next, the 6-hydroxyl is methylated with methyl iodide and the 2'-hydroxyl and the de-methylamine group becomes unprotected by hydrogenolysis. Finally, the amine group is methylated with formaldehyde in a reductive methylation. Since the publication of said patent document other alternative methods have been developed to obtain clarithromycin starting from erythromycin A. The common characteristic of said methods is to previously obtain the erythromycin A 9-oxime, which is protected together with the 2'-hydroxyl to subsequently proceed with the 6-hydroxyl methylation. These processes end with the unprotection of the oxime and the 2'-hydroxyl followed by the elimination of the oxime group by means of a NaHSO.sub.3 treatment. Said alternative methods differ in the protective group used to block the oxime group and the 2'-hydroxyl. Thus, alkoxy-carbonyl (EP 158.467) and benzyl or substituted benzyl groups (EP 195.960) have been used to protect both groups. A benzyl or substituted benzyl group and the 2'-hydroxyl have also blocked the oxime with a benzyloxycarbonyl group (EP 180.415) or with a trimethylsilyl group (EP 260.938). Subsequently, the use of a mixed acetal to protect the oxime group has been disclosed (U.S. Pat. No. 4,990,602), followed by the protection of the 2'-hydroxyl and 4"hydroxyl groups using trimethylsilylated derivatives and the 6-hydroxyl methylation with methyl iodide. The subsequent unprotection of the silyl groups and the acetal by means of a treatment with formic acid and elimination of the oxime group with Na.sub.2S.sub.2O.sub.5 would permit obtaining the clarithromycin, although said stages are not disclosed in said patent document U.S. Pat. No. 4,990,602. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Processes for preparing clarithromycin polymorphs and novel polymorph IV Inventor(s): Avrutov, Ilya; (Bat Hefer, IL), Borochovitz, Ronen; (Netanya, IL), Lifshitz, Igor; (Petach Tikva, IL), Masarwa, Basem; (Taibe, IL), Schwartz, Edi; (Rechovot, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020026038 Date filed: December 15, 2000 Abstract: The present invention relates to processes for converting clarithromycin Form 0 to clarithromycin Form II, which include slurrying clarithromycin the Form 0 in water. The present invention also relates to processes for the preparation of clarithromycin Form II by converting erythromycin A to clarithromycin and thereafter converting clarithromycin Form 0 to clarithromycin Form II by slurrying. The present invention further relates to the novel clarithromycin polymorph Form IV, a process for its
122
Erythromycin
preparation, pharmaceutical compositions comprising the compound, and methods of using the compound as a therapeutic agent. Excerpt(s): The present application claims the benefit of U.S. Provisional Application Ser. Nos. 60/171,839 filed on Dec. 22, 1999 and 60/171,221 filed on Dec. 16, 1999. The invention relates to methods for making polymorphic Form II of clarithromycin via slurrying polymorphic Form 0 of clarithromycin in water. The invention also relates to methods for making polymorphic Form IV of clarithromycin. By slurrying in water, clarithromycin Form 0 can be converted to clarithromycin Form II. Under different conditions, a novel polymorphic form of clarithromycin, designated Form IV can be formed. The invention relates to the use of clarithromycin polymorphs so formed in pharmaceutical compositions; and to methods of using them. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Steroid derived antibiotics Inventor(s): Li, Chunhong; (Provo, UT), Savage, Paul B.; (Springville, UT) Correspondence: John W. Freeman, ESQ.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020019376 Date filed: August 10, 2001 Abstract: A series of novel steroid derivatives are described. The steroid derivatives are antibacterial agents. The steroid derivatives also act to sensitize bacteria to other antibiotics including erythromycin and novobiocin. Excerpt(s): This is a continuation-in-part of PCT/US 98/04489, filed Mar. 6, 1998. The invention relates to novel steroid derivatives and processes and intermediates for the preparation of these compounds. Some compounds that associate strongly with the outer membrane of Gram-negative bacteria are known to disrupt the outer membrane and increase permeability. The increased permeability can increase the susceptibility of Gram-negative bacteria to other antibiotics. The best studied of this type of compound are the polymyxin antibiotics. For an example of a study involving the binding of polymyxin B to the primary constituent of the outer membrane of Gram-negative bacteria (lipid A) see: D. C. Morrison and D. M. Jacobs, Binding of Polymyxin B to The Lipid a Portion of Bacterial Lipopolysaccharides, Immunochemistry 1976, vol. 13, 813819. For an example of a study involving the binding of a polymyxin derivative to Gram-negative bacteria see: M. Vaara and P. Viljanen, Binding of Polymyxin B Nonapeptide to Gram-negative Bacteria, Antimicrobial Agents and Chemotherapy, 1985, vol. 27, 548-554. 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 erythromycin, 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 “erythromycin” (or synonyms)
Patents 123
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 erythromycin. You can also use this procedure to view pending patent applications concerning erythromycin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
125
CHAPTER 7. BOOKS ON ERYTHROMYCIN Overview This chapter provides bibliographic book references relating to erythromycin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on erythromycin include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “erythromycin” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “erythromycin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “erythromycin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Informing patients about drugs--analysis of alternative designs for erythromycin leaflets; ISBN: 0833003496; http://www.amazon.com/exec/obidos/ASIN/0833003496/icongroupinterna
•
NTP technical report on the toxicology and carcinogenesis studies of Erythromycin stearate (CAS no. 643-22-1) in F344/N rats and B6C3F b1 s mice (feed studies) (SuDoc HE 20.3159/2:338) by U.S. Dept of Health and Human Services; ISBN: B000102KH0; http://www.amazon.com/exec/obidos/ASIN/B000102KH0/icongroupinterna
126
Erythromycin
Chapters on Erythromycin In order to find chapters that specifically relate to erythromycin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and erythromycin 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 “erythromycin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on erythromycin: •
Antibiotics for Oral and Maxillofacial Infections Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 157-173. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: Infections of the oral and maxillofacial region, although commonly encountered by dentists, can be challenging to manage. This chapter on antibiotics for the treatment of oral and maxillofacial infections is from a textbook that integrates basic facts and principles of antibiotic therapy with recently-emerged concepts of care. The author presents guidelines for using a combination of antibiotics and surgery to manage minor orofacial and odontogenic (arising from the tissues that produce teeth) infections in the office setting. Topics include the microbiology of odontogenic infections; the natural course of odontogenic infections, i.e., cellulitis, abscess, and sinus tract; the spread of infection; the role of depressed host defenses, due to chemotherapy, metabolic diseases, organ transplants, or myeloproliferative diseases; and the use of dental spectrum antibiotics, including penicillin, extended spectrum penicillins, cephalosporins, erythromycin, clarithromycin, clindamycin, tetracycline, metronidazole, and fluoroquinolones. The author also reviews the principles of therapy, including determination of severity of the infection, evaluation of host defenses, surgical treatment, antibiotic choice, antibiotic administration, follow up, and side effects and secondary infection. The chapter concludes with a discussion of wound infection prophylaxis and special considerations, including sinus perforations, avulsed teeth, osteomyelitis, dry socket (alveolar osteitis), pericoronitis, routine extractions, and impacted third molars (wisdom teeth). Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 3 figures. 4 tables. 7 references.
•
Gastric Motor Disorders Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 247-259. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700.
Books
127
Summary: Motor disorders of the stomach are common, varied in their clinical presentation, and may present with symptoms suggestive of impaired storage or impaired emptying of chyme. This chapter, from a gastroenterology yearbook, reviews the disorders associated with delayed gastric emptying and the treatment approach in these patients. The authors focus on established prokinetic agents in the treatment of gastric motor disorders. Remarkable technologic advances over the past decade have provided an expanding number of diagnostic and therapeutic modalities, which warrant a systematic approach in their use. Therapy is symptomatic and should be directed at the underlying pathologic process whenever possible. In addition to addressing nutritional and antiemetic needs, therapy frequently includes use of one or more of an expanding number of prokinetic drugs to enhance and coordinate gastroduodenal motility. Drugs discussed include metoclopramide (Reglan), domperidone (Motilium), cisapride (Propulsid), erythromycin, 5-HT3 receptor antagonists and 5-HT4 receptor agonists, opiate receptor antagonists, gonadotropinreleasing hormone agonists, and cholecystokinin receptor antagonists. 3 tables. 68 references. (AA-M). •
Drugs and the Liver Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.335-363. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: The liver is particularly concerned with drug metabolism, and especially of drugs given orally. Drugs can cause toxic effects that can mimic almost every naturally occurring liver disease in man. This chapter on drugs and the liver is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter is organized into specific pathologies and their potential causes: hepato-cellular zone 3 necrosis, due to carbon tetrachloride, Amanita mushrooms, paracetamol (acetaminophen), salicylates, hyperthermia, hypothermia, and burns; hepato-cellular zone 1 necrosis, due to ferrous sulfate or phosphorus; mitochondrial cytopathies, due to sodium valproate, tetracyclines, tacrine, antiviral nucleoside analogues, and Bacillus cereus; steatohepatitis, due to perhexiline maleate, amiodarone, synthetic estrogens, and calcium channel blockers; fibrosis, due to methotrexate, other cytotoxic drugs, arsenic, vinyl chloride, vitamin A, and retinoids; vascular changes, due to sinusoidal dilatation, peliosis hepatitis, and veno-occlusive disease (VOD); acute hepatitis, due to isoniazid, methyl dopa, halothane, hydrofluorocarbons, systemic antifungals, oncology drugs, nervous system modifiers, sustained-release nicotinic acid (niacin), sulfonamides and derivatives, nonsteroidal anti-inflammatory drugs, antithyroid drugs, quinidine and quinine, troglitazone, and anti-convulsants; chronic hepatitis, due to herbal remedies and recreational drugs; canalicular cholestasis, due to cyclosporine A and ciprofloxacin; hepato-canalicular cholestasis, due to chlorpromazine, penicillins, sulfonamides, erythromycin, haloperidol, cimetidine and ranitidine, oral hypoglycemic agents, tamoxifen, other causes, and dextropropoxyphene; ductular cholestasis; biliary sludge; sclerosing cholangitis; hepatic nodules and tumors; and hepatocellular carcinoma (HCC, liver cancer). 28 figures. 5 tables. 170 references.
128
•
Erythromycin
Antimicrobials in Pediatric Dentistry Source: in Pinkham, J.R., et al., eds. Pediatric Dentistry: Infancy Through Adolescence. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 104-112. Contact: Available from W.B. Saunders Company. Book Orders Fulfillment Department, Harcourt Health Sciences, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522. Website: www.wbsaunders.com. PRICE: $69.00 plus shipping and handling. ISBN: 0721682383. Summary: The second most commonly prescribed group of drugs for use in dentistry (after local anesthetics) are antibiotics. Treatment of infections usually involves a definitive dental or surgical procedure and often requires the use of antibiotics. This chapter on antimicrobials is from a textbook on pediatric dentistry. Antibiotics are indicated for diseases in which a specific microbial agent has been identified, for a clinical situation that points clearly to a probable microbial cause, and for use as a lifesaving measure in a gravely ill patient. Prophylactic (preventive) use of antibiotics is also indicated in some specific instances, such as prophylaxis against bacterial endocarditis for patients with congenital heart disease. This chapter covers antimicrobial classification, including microbial target category, mode of action, bactericidal versus bacteriostatic antibiotics, and resistance; antibiotic agents, including penicillins, erythromycin, and cephalosporins; bacterial encarditis prophylaxis; antifungal agents; and antiviral agents. 8 tables. 7 references.
•
Medications Used To Treat Complications of Diabetes Source: in Carlisle, B.A.; Kroon, L.A.; Koda-Kimble, M.A. 101 Medication Tips for People with Diabetes. Alexandria, VA: American Diabetes Association. 1999. p. 66-75. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400329. Order number 483301. Summary: This chapter answers questions about the meditations used to treat diabetes complications, including nonprescription analgesics, tricyclic antidepressants, capsaicin cream, angiotensin converting enzyme (ACE) inhibitors, laxatives, and calcium channel blockers. Nonprescription analgesics, antidepressants, and narcotic analgesics can be used to treat the pain associated with diabetic neuropathy. Capsaicin cream, a chemical found in hot chili peppers, can be applied to the feet to relieve pain. ACE inhibitors can be used to treat microalbuminuria, an early sign of kidney damage. The symptoms of gastroparesis, a condition that affects the nerves of the stomach, can be treated with metoclopramide, cisapride, and erythromycin. These medications increase the stomach's ability to contract and aid in digestion. Constipation can be treated by increasing the amount of fluid and fiber in a person's diet. Laxatives may also be useful in treating constipation. Men who have diabetes and experience impotence can use the medications alprostadil and sildenafil to maintain an erection. People who have diabetes and high blood pressure can be treated with ACE inhibitors, diuretics, and calcium channel blockers. Angiotensin receptor II antagonists and calcium channel blockers can be used to treat kidney disease. People who have diabetes should take any medications their doctor prescribes for other conditions, such as high blood pressure, heart disease, high cholesterol or triglycerides, obesity, and insulin resistance.
Books
•
129
Considerations for Female Patients Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 235-242. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: This chapter discusses side effects and risks associated with the use of antibiotics and antimicrobials in women, with an emphasis on the effects of such treatment on pregnant and lactating women. The chapter is from a textbook that integrates basic facts and principles of antibiotic therapy with recently-emerged concepts of care. The author discusses considerations for antibiotic prescriptions, including vaginitis (a common side effect), and contraceptive failure; antibiotics that cross the placenta and reach the fetus; specific antibiotics and their effects in pregnant and lactating women, including penicillins, tetracycline, cephalosporins, erythromycin, clindamycin, metronidazole, azithromycin, aminoglycosides, sulfonamides, and chloramphenicol; periodontal considerations; and a final note on oral pain medications for pregnant or lactating women who are undergoing dental treatment. Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 1 figure. 2 tables. 33 references.
•
Medical and Surgical Treatment of Cochlear Hearing Loss Source: in Valente, M.; Hosford-Dunn, H.; Roeser, R.J., eds. Audiology: Treatment. New York, NY: Thieme. 2000. p. 377-396. Contact: Available from Thieme. 333 Seventh Avenue, New York, NY 10001. (800) 7823488. Fax (212) 947-0108. E-mail:
[email protected]. PRICE: $69.00 plus shipping and handling. ISBN: 0865778590. Summary: This chapter on the medical and surgical management of cochlear hearing loss is from a textbook that provides a comprehensive overview of the numerous treatment options available to help patients relieve the clinical symptoms seen in an audiology practice. Cochlear hearing loss may be caused by a wide variety of medical problems; it is the responsibility of the practitioner to identify the cause of hearing loss and to evaluate the other potential associated medical ramifications to treat the patient as a whole. Topics covered include metabolic disorders, including Meniere's disease, diabetes mellitus, renal disease, hypothyroidism, and cochlear otosclerosis; immunologic disorders, including autoimmune inner ear disease, Cogan's syndrome, polyarteritis nodosa, Vogt Koyanagi Harada syndrome, Wegener's granulomatosis, sarcoidosis, and postapedectomy granuloma; ototoxicity, including that from aminoglycoside antibiotics, erythromycin, vancomycin, other antibiotics, loop diuretics, antineoplastic (chemotherapy) agents, antiinflammatory agents, and antimalarials; trauma, including temporal bone fractures, noise trauma, and barotrauma (from barometric pressure changes); infections, including cytomegalovirus, toxoplasmosis, congenital rubella, mumps, measles, Varicella Zoster virus, HIV, other viruses and Mycoplasma, meningitis, labyrinthitis, fungal infections, and syphilis; malignancy; presbycusis; sudden idiopathic sensorineural hearing loss; and hereditary or development causes. The authors stress that complete audiological assessments are crucial in the initial evaluation and subsequent therapeutic monitoring of sensorineural hearing losses. The chapter includes an outline of the topic covered, a list of references, a
130
Erythromycin
summary outline of the related preferred practice guidelines, and various 'pearls and pitfalls' offering practical advice to the reader. 11 figures. 1 table. 67 references. •
Chapter 199: Sebaceous Gland Disorders Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 5 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have sebaceous gland disorders with information on the symptoms and treatment of acne, rosacea, perioral dermatitis, and sebaceous cysts. Acne is a common skin condition in which dried sebum, flaked skin, and bacteria collect in skin pores, forming a comedo, which blocks sebum from flowing from hair follicles up through the pores. Acne is often worse in the winter and better in the summer. Diet has little or no effect. Acne may also appear with each menstrual period in young women and may clear up or worsen during pregnancy. Certain cosmetics may aggravate acne. Superficial acne can be made worse by squeezing pimples or trying to open them in other ways. It can be treated by applying the antibiotic clindamycin or erythromycin to the skin. Certain oral antibiotics can reduce or prevent superficial acne. Sunlight can help because it dries the skin and causes slight scaling. Other helpful topical agents are benzoyl peroxide and preparations containing sulfur resorcinol. Deep acne is treated with an oral antibiotic or oral isotretinoin if antibiotics are ineffective. Although isotretinoin is very effective, it can have serious side effects, so a person taking this drug must be monitored. Rosacea is a persistent skin disorder of unknown etiology that produces redness, tiny pimples, and broken blood vessels, usually on the central area of the face. Treatment involves avoiding foods that cause blood vessels to dilate, taking oral antibiotics, and applying topical antibiotics. Perioral dermatitis, a red, often bumpy rash around the mouth and on the chin, can be caused by corticosteroids and by some oily cosmetics. Oral tetracyclines are usually the best treatment. Sebaceous cysts are yellowish or flesh colored bumps that contain dead skin, skin excretions, and other skin particles. These cysts are treated by either puncturing the top with a needle or cutting the top off with a scalpel, then squeezing out the contents. 1 figure.
•
Gastroparesis Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 269-279. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter, from a gastroenterology yearbook, covers gastroparesis, a chronic motility disorder of the stomach caused by delayed transit of intraluminal contents from the stomach into the duodenum in the absence of mechanical obstruction. Symptoms of gastroparesis include early satiety, postprandial (after a meal) abdominal bloating or distension, nausea often accompanied by vomiting, and abdominal pain. The three most common causes of gastroparesis are diabetes mellitus, prior surgery for peptic ulcer disease, and idiopathic (i.e., gastroparesis with no obvious cause). The authors then discuss methods of measuring gastric emptying and motility, including the upper gastrointestinal tract radiographic series, intraluminal gastropyloroduodenal
Books
131
manometry, radionuclide gastric emptying scintigraphy, and electrogastrogram. The treatment of gastroparesis varies depending on the setting in which a patient is initially seen. In an ambulatory outpatient complaining of early satiety and abdominal distension, treatment may merely consist of prescribing an oral prokinetic agent. In severe cases with nausea, vomiting, and signs of dehydration and poor glucose control, however, treatment may require hospital admission, intravenous hydration, careful regulation of blood glucose, nasogastric decompression, and intravenous administration of prokinetic agents. The goals of treatment are to reduce symptoms and maintain hydration and nutrition. Prokinetic agents discussed include metoclopramide, cisapride, erythromycin, bethanechol, and domperidone. The author concludes that the application of surgical treatment with gastric pacing or gastric resection to improve symptoms is starting to be developed. 2 figures. 4 tables. 15 references. (AA-M). •
Diagnosis and Management of Gastric Emptying Disorders Source: in Cameron, J.L., et al., eds. Advances in Surgery. Vol 27. St. Louis, MO: MosbyYear Book, Inc. 1994. p. 233-255. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail:
[email protected]. PRICE: Contact directly for current price. ISBN: 815114923. ISSN: 00653411. Summary: This chapter, from a textbook on surgery, describes the relevant physiology and pathophysiology of gastric emptying. In addition, the authors discuss the diagnosis and management of gastric emptying disorders. Gastric emptying, the final common pathway for gastric secretory and motor events, is the net result of coordinated contraction and relaxation of the stomach, pylorus, and duodenum. Functional changes in the gastroduodenal musculature may result from primary neuromuscular disorders or systemic metabolic diseases, while surgical denervation, bypass, and resection results in structural and mechanical changes in the gastroduodenum. Gastric emptying disorders covered include dumping syndrome and delayed gastric emptying. Dumping symptoms may occur in up to 50 percent of postgastrectomy patients, but most patients are treated satisfactorily by dietary manipulation or, in the rare incapacitated patient, by the long-acting somatostatin analogue octreotide. Reconstructive gastric surgery may rarely be indicated to slow gastric emptying and alleviate the dumping syndrome. Pharmacologic therapy of delayed gastric emptying has seen the introduction of several new and promising prokinetic agents, including bethanechol, metoclopramide, cisapride, domperidone, motilin, and erythromycin. In addition, surgical intervention for mechanical causes of gastric outlet obstruction is readily justified. 4 figures. 1 table. 106 references. (AA-M).
133
CHAPTER 8. PERIODICALS AND NEWS ON ERYTHROMYCIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover erythromycin.
News Services and Press Releases One of the simplest ways of tracking press releases on erythromycin 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 “erythromycin” (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 erythromycin. 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 “erythromycin” (or synonyms). The following was recently listed in this archive for erythromycin: •
Erythromycin improves esophageal and gastric motility in diabetics Source: Reuters Medical News Date: June 23, 2003
•
Erythromycin improves gastric motility in critically injured patients Source: Reuters Industry Breifing Date: October 18, 2002
134
Erythromycin
•
Early exposure to erythromycin may increase risk of pyloric stenosis Source: Reuters Medical News Date: July 30, 2002
•
Erythromycin facilitates early enteral nutrition in ventilated patients Source: Reuters Medical News Date: July 29, 2002
•
Erythromycin-resistant streptococci outbreak described in US schoolchildren Source: Reuters Medical News Date: April 18, 2002
•
Erythromycin prevents exacerbations in COPD patients Source: Reuters Industry Breifing Date: October 12, 2001
•
Neonatal treatment with systemic erythromycin linked to infantile pyloric stenosis Source: Reuters Industry Breifing Date: October 04, 2001
•
Penicillin and erythromycin antagonistic against S. pneumoniae in mice Source: Reuters Industry Breifing Date: January 08, 2001
•
Case of primary biliary cirrhosis after erythromycin therapy documented Source: Reuters Medical News Date: July 17, 2000
•
Pyloric stenosis risk linked to erythromycin prophylaxis for pertussis Source: Reuters Medical News Date: December 20, 1999
•
Standard dose of IV erythromycin can have antiarrhythmic effects Source: Reuters Medical News Date: April 22, 1999
•
Women at higher risk than men of erythromycin-associated arrhythmias Source: Reuters Medical News Date: November 25, 1998
•
Erythromycin may protect against cellular hypoxia in the central nervous system Source: Reuters Medical News Date: October 22, 1998
•
Erythromycin, verapamil increase serum concentration of simvastatin Source: Reuters Medical News Date: September 14, 1998
•
Chancroid responds equally well to erythromycin, ciprofloxacin Source: Reuters Medical News Date: July 09, 1998
•
Decrease In Erythromycin Resistance Follows Reduced Macrolide Use Source: Reuters Medical News Date: August 14, 1997
•
Povidone-Iodine Eye Drops More Effective Than Silver Nitrate Or Erythromycin As Prophylaxis Against Ophthalmia Neonatorum Source: Reuters Medical News Date: March 07, 1995
Periodicals and News
135
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 “erythromycin” (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 “erythromycin” (or synonyms). If you know the name of a company that is relevant to erythromycin, 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 “erythromycin” (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
136
Erythromycin
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 “erythromycin” (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 erythromycin: •
Prokinetic Drugs and Gastrointestinal Motility Source: Lifeline Letter. 16(2): 1-2. March/April 1995. Contact: Available from Oley Foundation, A-23, Hun Memorial, Albany Medical Center, Albany, NY 12208. (800) 776-OLEY or (518) 262-5079. Summary: This article, from a newsletter for people living with home parenteral and/or enteral nutrition, explains prokinetic drugs and gastrointestinal motility. The article provides information about the causes of motility disorders; symptoms; and the role of prokinetic drugs, including cisapride, metoclopramide, erythromycin, and bethanechol. The author cautions that sensory, psychological, and social factors (the 'brain-gut connection') may all influence the clinical response to prokinetic drug therapy. 1 figure. (AA-M).
Academic Periodicals covering Erythromycin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to erythromycin. In addition to these sources, you can search for articles covering erythromycin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
137
CHAPTER 9. 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 erythromycin. 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 erythromycin. 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
138
Erythromycin
following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to erythromycin: Erythromycin •
Ophthalmic - U.S. Brands: Ilotycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202220.html
Erythromycin and Benzoyl Peroxide •
Topical - U.S. Brands: Benzamycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202222.html
Erythromycin and Sulfisoxazole •
Systemic - U.S. Brands: Eryzole; Pediazole http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202224.html
Erythromycins •
Systemic - U.S. Brands: E.E.S.; E-Base; E-Mycin; ERYC; EryPed; Ery-Tab; Erythro; Erythrocin; Erythrocot; Ilosone; Ilotycin; My-E; PCE; Wintrocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202223.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,
Researching Medications
139
Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
141
APPENDICES
143
APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
144
Erythromycin
•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources
145
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
146
Erythromycin
•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “erythromycin” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 20206 70 996 421 87 21780
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “erythromycin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
Physician Resources
147
Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
149
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 erythromycin 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 erythromycin. 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 erythromycin. 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 “erythromycin”:
150
•
Erythromycin
Other guides Acne http://www.nlm.nih.gov/medlineplus/acne.html Chlamydia Infections http://www.nlm.nih.gov/medlineplus/chlamydiainfections.html Sinusitis http://www.nlm.nih.gov/medlineplus/sinusitis.html Skin Diseases http://www.nlm.nih.gov/medlineplus/skindiseases.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 erythromycin. 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: •
Chlamydia : Questions and Answers Contact: Planned Parenthood of Federation of America Incorporated, PO Box 4457, New York, NY, 10163-4457, (800) 669-0156, http://www.plannedparenthood.org. Summary: This brochure presents general information about chlamydia using a question and answer format. The brochure presents the general symptoms of chlamydia and methods of transmission including unprotected vaginal or anal sex. Chlamydia is the most common sexually transmitted disease (STD) in the United States (US), and can lead to the development of pelvic inflammatory disease (PID), a condition that can block fallopian tubes in women. The symptoms of PID in women include longer and/or heavier periods, more cramping during periods, abnormal mucus discharge, lower abdomen pain, tiredness, weakness, fever, vomiting, and/or pain during vaginal intercourse or a pelvic exam. Chlamydia also can cause sterility or Reiter's syndrome in men. Chlamydia can be passed to infants from their mothers during pregnancy or childbirth leading to neonatal conjunctivitis, chlamydia pneumonia, miscarriage, or stillbirth. It can be diagnosed through a cervical exam; lab tests of cells from the penis, cervix, urethra, or anus; or tests of urine samples. Chlamydia can be treated easily using antibiotics such as doxycycline, azithromycin, ofloxacin, erythromycin, or erythromycin ethylsuccinate. Persons with chlamydia should adhere to their medical regimen, undergo follow-up visits with their physicians, and get their partner(s) treated at the
Patient Resources
151
same time. Persons who have a number of different sex partners, who don't use condoms, or who have a history of other STDs are most likely to get chlamydia. Persons with chlamydia can avoid spreading their infection to others by informing their sex partners about their condition, avoiding sex until treatment is complete, getting their partners tested and treated at the same time, and using female or male condoms during each sexual activity. Persons can prevent getting chlamydia by practicing safer sex or abstaining from intercourse altogether. Birth control pills may increase women's chances for contracting this STD, therefore, they should also use a male or female condoms. Concerned individuals can get tested for chlamydia at Planned Parenthood centers, their doctors' offices, health departments, and clinics. •
Gastroparesis and Diabetes Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse (NDDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. 1999. 5 p. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail:
[email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text available online at no charge; single copy free; bulk orders available. Order number: DM-196. Summary: This fact sheet provides information on the symptoms, complications, causes, diagnosis, and treatment of gastroparesis. This disorder, which is often a complication of type 1 diabetes, occurs when nerves to the stomach are damaged or stop working. As a result, the stomach takes too long to empty. Symptoms include nausea, vomiting, an early feeling of fullness when eating, weight loss, and abdominal bloating and discomfort. Complications of gastroparesis include the formation of bacterial overgrowth and the development of bezoars. Although diabetes is one cause of gastroparesis, medications and other disorders may cause it. The diagnosis of gastroparesis may be confirmed through various tests, including barium x ray, barium beefsteak meal, radioisotope gastric-emptying scan, gastric manometry, blood tests, upper endoscopy, and ultrasound. The primary treatment goal for gastroparesis related to diabetes is to regain control of blood glucose levels through use of insulin; oral medications such as metoclopramide, cisapride, erythromycin, and domperidone; meal and food changes; feeding tubes; or intravenous feeding. The fact sheet concludes with information on the National Digestive Diseases Information Clearinghouse. 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 erythromycin. 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.
152
Erythromycin
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 erythromycin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with erythromycin. 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 erythromycin. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “erythromycin” (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
Patient Resources
153
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 “erythromycin”. 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 “erythromycin” (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 “erythromycin” (or a synonym) into the search box, and click “Submit Query.”
155
APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
22
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
156
Erythromycin
libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 157
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
158
Erythromycin
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 159
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
160
Erythromycin
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
161
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
163
ERYTHROMYCIN 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] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: A localized, circumscribed collection of pus. [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] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Aclarubicin: An anthracycline antibiotic produced by Streptomyces galilaeus. It has potent antineoplastic activity, especially in the treatment of leukemias, with reduced cardiac toxicity in comparison to daunorubicin or doxorubicin. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature
164
Erythromycin
blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell
Dictionary 165
respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH]
166
Erythromycin
Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alprostadil: A potent vasodilator agent that increases peripheral blood flow. It inhibits platelet aggregation and has many other biological effects such as bronchodilation, mediation of inflammation, etc. [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] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [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] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of
Dictionary 167
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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] 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] 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] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Animal Husbandry: The science of breeding, feeding, and care of domestic animals; includes housing and nutrition. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or
168
Erythromycin
reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [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] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [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] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic
Dictionary 169
and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] 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] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]
Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH]
170
Erythromycin
Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Atrial: Pertaining to an atrium. [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] Audiology: The study of hearing and hearing impairment. [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] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, 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 Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Proteins: Proteins found in any species of bacterium. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barotrauma: Injury following pressure changes; includes injury to the eustachian tube, ear drum, lung and stomach. [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] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Dictionary 171
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoyl Peroxide: A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy. It is used also as a bleach in the food industry. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [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. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bethanechol: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, cardiac rate changes, and bronchial spasms. [NIH] Bezoars: Concretions of swallowed hair, fruit or vegetable fibers, or similar substances found in the alimentary canal. [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] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH]
172
Erythromycin
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] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists
Dictionary 173
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] 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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad Ligament: A broad fold of peritoneum that extends from the side of the uterus to the wall of the pelvis. [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] Bronchial Spasm: Spasmodic contraction of the smooth muscle of the bronchi. [NIH] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [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
174
Erythromycin
weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Campylobacter: A genus of bacteria found in the reproductive organs, intestinal tract, and oral cavity of animals and man. Some species are pathogenic. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Carbimazole: An imidazole antithyroid agent. Carbimazole is metabolized to methimazole, which is responsible for the antithyroid activity. [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] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH]
Dictionary 175
Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [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 Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] 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] 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] Cephaloridine: A cephalosporin antibiotic. [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] Cephalothin: A cephalosporin antibiotic. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] 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
176
Erythromycin
infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [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 unless quickly treated. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus. [NIH]
Chorion: The outermost extraembryonic membrane. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chyme: A thick liquid made of partially digested food and stomach juices. This liquid is made in the stomach and moves into the small intestine for further digestion. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated
Dictionary 177
by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]
Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [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] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [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] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] 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 trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cloxacillin: A semi-synthetic antibiotic that is a chlorinated derivative of oxacillin. [NIH] Coagulants: Exogenous substances used to promote blood coagulation. The endogenous blood coagulation factors are considered to be coagulants only when administered as drugs. [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.
178
Erythromycin
[NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comedo: A plug of keratin and sebum within the dilated orifice of a hair follicle, frequently containing the bacteria Propionibacterium acnes, Staphylococcus albus, and Pityrosporon ovale; called also blackhead. [EU] 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
Dictionary 179
activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [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] 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]
180
Erythromycin
Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] 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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause
Dictionary 181
sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [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] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]
Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling
182
Erythromycin
it rapidly causes the two complementary strands to separate. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids 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]
Dentists: Individuals licensed to practice dentistry. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] 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] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilate: Relax; expand. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or
Dictionary 183
in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] 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] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]
symptoms
resulting
from
an
absent
or
Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]
184
Erythromycin
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] Dyspepsia: Impaired digestion, especially after eating. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emetic: An agent that causes vomiting. [EU] 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] 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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] 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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous)
Dictionary 185
production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [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] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [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] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epirubicin: An anthracycline antibiotic which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, pancreatic cancer, gastric cancer, small-cell lung cancer and acute leukemia. It is equal in activity to doxorubicin but exhibits less acute toxicities and less cardiotoxicity. [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
186
Erythromycin
covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Ergotamine: A vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine headaches. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [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] Erythromycin Estolate: A macrolide antibiotic, produced by Streptomyces erythreus. It is the lauryl sulfate salt of the propionic ester of erythromycin. This erythromycin salt acts primarily as a bacteriostatic agent. 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] Erythromycin Ethylsuccinate: A macrolide antibiotic, produced by Streptomyces erythreus. This compound is an ester of erythromycin base and succinic acid. It acts primarily as a bacteriostatic agent. 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] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagectomy: An operation to remove a portion of the esophagus. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH]
Dictionary 187
Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [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] Evacuation: An emptying, as of the bowels. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [NIH] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] 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] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH]
188
Erythromycin
Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [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 carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is
Dictionary 189
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] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [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] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gastric: Having to do with the stomach. [NIH] Gastric Bypass: Surgical procedure in which the stomach is transected high on the body. The resulting proximal remnant is joined to a loop of the jejunum in an end-to-side anastomosis. This procedure is used frequently in the treatment of morbid obesity. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastric Outlet Obstruction: The hindering of output from the stomach to the small intestine. The source varies: peptic ulcer, foreign bodies, aging, neoplasms, etc. [NIH] Gastric Resection: An operation to remove part or all of the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH]
190
Erythromycin
Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic 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] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH]
Dictionary 191
Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] 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] 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] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] 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-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] 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
192
Erythromycin
of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] 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] 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] 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] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU]
Dictionary 193
Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [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] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH]
194
Erythromycin
Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] 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] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH]
Dictionary 195
Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [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] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impetigo: A common superficial bacterial infection caused by staphylococcus aureus or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [NIH] Impotence: The inability to perform sexual intercourse. [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] 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] 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] 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]
196
Erythromycin
Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] 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] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] 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] Interindividual: Occurring between two or more individuals. [EU] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] 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]
Dictionary 197
Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese
198
Erythromycin
soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] 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] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [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] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous 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]
Dictionary 199
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] 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] Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Neoplasms: Tumors or cancer of the liver. [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] 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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] 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.
200
Erythromycin
These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] 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] Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manometry: Tests that measure muscle pressure and movements in the GI tract. [NIH] Mastoiditis: Inflammation of the cavity and air cells in the mastoid part of the temporal bone. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH]
Dictionary 201
Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methimazole: A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Mineralization: The action of mineralizing; the state of being mineralized. [EU] Miocamycin: A macrolide antibiotic that has a wide antimicrobial spectrum and is particularly effective in respiratory and genital infections. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the
202
Erythromycin
second trimester. [NIH] Miscible: Susceptible of being mixed. [EU] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] 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] Motilin: A 22-amino acid polypeptide (molecular weight 2700) isolated from the duodenum. At low pH it inhibits gastric motor activity, whereas at high pH it has a stimulating effect. [NIH]
Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [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] 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] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells,
Dictionary 203
water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [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] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [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] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH]
204
Erythromycin
Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [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] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nizatidine: A histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion. The drug is used for the treatment of duodenal ulcers. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Novobiocin: An antibiotic drug used to treat infection. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a
Dictionary 205
mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oleandomycin: Antibiotic substance produced by Streptomyces antibioticus. [NIH] Oncology: The study of cancer. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] 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] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] 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] Ori region: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Oropharynx: Oral part of the pharynx. [NIH]
206
Erythromycin
Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] 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] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [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] 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] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxacillin: An antibiotic similar to flucloxacillin used in resistant staphylococci infections. [NIH]
Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreaticoduodenectomy: The excision of the head of the pancreas and the encircling loop
Dictionary 207
of the duodenum to which it is connected. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [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] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] 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]
Pediatric Dentistry: The practice of dentistry concerned with the dental problems of children, proper maintenance, and treatment. The dental care may include the services provided by dental specialists. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH]
208
Erythromycin
Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [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] 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] Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [NIH] Pericoronitis: Inflammation of the gingiva surrounding the crown of a tooth. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perioral: Situated or occurring around the mouth. [EU] 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] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Pernicious: Tending to a fatal issue. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [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
Dictionary 209
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] P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphoric Acids: Inorganic derivatives of phosphoric acid (H3PO4). Inorganic salts are known as phosphates and organic esters are phosphoric acid esters. [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] Phosphorylated: Attached to a phosphate group. [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] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH]
210
Erythromycin
Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] 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]
Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polyarthritis: An inflammation of several joints together. [EU] 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]
Dictionary 211
Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portosystemic Shunt: An operation to create an opening between the portal vein and other veins around the liver. [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] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Presbycusis: Progressive bilateral loss of hearing that occurs in the aged. Syn: senile deafness. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH]
212
Erythromycin
Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, 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] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prokinetic Drugs: Medicines that cause muscles in the GI tract to move food. An example is cisapride (SIS-uh-pryd) (Propulsid). [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]
Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids
Dictionary 213
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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [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] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and
214
Erythromycin
treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] 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]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyloric Sphincter: The muscle between the stomach and the small intestine. [NIH] Pyloric Stenosis: Obstruction of the pyloric canal. [NIH] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH]
Dictionary 215
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] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Replication Origin: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which
216
Erythromycin
gives very efficient initiation of replication. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [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] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribonuclease: RNA-digesting enzyme. [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] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often
Dictionary 217
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] Ruminants: A suborder of the order Artiodactyla whose members have the distinguishing feature of a four-chambered stomach. Horns or antlers are usually present, at least in males. [NIH]
Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] 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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Scalpel: A small pointed knife with a convex edge. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [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]
218
Erythromycin
Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] 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] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silanes: Compounds similar to hydrocarbons in which a tetravalent silicon atom replaces the carbon atom. They are very reactive, ignite in air, and form useful derivatives. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] 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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
Dictionary 219
Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
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] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including
220
Erythromycin
spermatocytogenesis and spermiogenesis. [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] Spiramycin: A macrolide antibiotic produced by Streptomyces ambofaciens. The drug is effective against gram-positive aerobic pathogens, N. gonorrhoeae, and staphylococci. It is used to treat infections caused by bacteria and Toxoplasma gondii. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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] Stillbirth: The birth of a dead fetus or baby. [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] Stool: The waste matter discharged in a bowel movement; feces. [NIH]
Dictionary 221
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] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Styptic: Astringent. [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] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by
222
Erythromycin
means of a tube and a device that acts on negative pressure. [NIH] Sulfadiazine: A short-acting sulfonamide used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [NIH] Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [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] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Talcum: A native magnesium silicate. [NIH] Talcum powder: A native magnesium silicate. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Taxanes: Anticancer drugs that inhibit cancer cell growth by stopping cell division. Also called antimitotic or antimicrotubule agents or mitotic inhibitors. [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] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of
Dictionary 223
extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetravalent: Pertaining to a group of 4 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] 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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a
224
Erythromycin
bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tonsils: Small masses of lymphoid tissue on either side of the throat. [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] Torsades de Pointes: A ventricular tachycardia characterized by periodic twisting of the points of the QRS complexes and rates between 200 and 250 beats per minute. It may be selflimited or may progress to ventricular fibrillation. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] 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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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]
Dictionary 225
Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tretinoin: An important regulator of gene expression, particularly during growth and development and in neoplasms. Retinoic acid derived from maternal vitamin A is essential for normal gene expression during embryonic development and either a deficiency or an excess can be teratogenic. It is also a topical dermatologic agent which is used in the treatment of psoriasis, acne vulgaris, and several other skin diseases. It has also been approved for use in promyelocytic leukemia. [NIH] Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Tylosin: Macrolide antibiotic obtained from cultures of Streptomyces fradiae. The drug is effective against many microorganisms in animals but not in humans. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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] Ureaplasma: A genus of gram-negative, nonmotile bacteria which are common parasitic inhabitants of the urogenital tracts of man, cattle, dogs, and monkeys. [NIH] Ureaplasma urealyticum: A species of gram-negative bacteria found in the human genitourinary tract, oropharynx, and anal canal. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH]
226
Erythromycin
Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH]
Dictionary 227
Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virginiamycin: A cyclic polypeptide antibiotic complex from Streptomyces virginiae, S. loidensis, S. mitakaensis, S. pristina-spiralis, S. ostreogriseus, and others. It consists of 2 major components, virginiamycin Factor M1 and virginiamycin Factor S1. It is used to treat infections with gram-positive organisms and as a growth promoter in cattle, swine, and poultry. [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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Voriconazole: A drug that treats infections caused by fungi. [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.
228
Erythromycin
[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] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zinc Acetate: A salt produced by the reaction of zinc oxide with acetic acid and used as an astringent, styptic, and emetic. [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]
229
INDEX A Abdomen, 150, 163, 172, 173, 197, 199, 206, 207, 220, 223 Abdominal, 58, 94, 116, 130, 151, 163, 171, 197, 206 Abdominal Pain, 130, 163 Abortion, 163, 211, 227 Abscess, 60, 126, 163 Acceptor, 163, 206, 222, 224 Acetaminophen, 10, 70, 127, 163 Acetylcholine, 163, 176, 204 Acetylcysteine, 95, 163 Acidity, 63, 163 Aclarubicin, 93, 163 Acne, 46, 47, 55, 65, 71, 78, 81, 105, 106, 130, 150, 163, 171, 197, 216, 225 Acne Vulgaris, 46, 71, 81, 163, 197, 225 Acremonium, 163, 175 Acute myelogenous leukemia, 163, 164 Acute myeloid leukemia, 17, 163, 164, 212 Acute nonlymphocytic leukemia, 163, 164 Acute renal, 164, 192 Acyl, 6, 14, 101, 117, 164 Adaptation, 27, 164, 176, 203 Adenine, 164 Adenocarcinoma, 164, 193 Adenosine, 98, 106, 164, 166, 209, 223 Adenosine Deaminase, 98, 106, 164 Adenovirus, 27, 164 Adjustment, 164 Adrenal Cortex, 164, 212 Adrenal Medulla, 164, 185 Adrenergic, 164, 168, 183, 186, 214 Adsorption, 113, 164 Adsorptive, 164 Adverse Effect, 164, 197, 218, 227 Aerobic, 32, 35, 164, 165, 194, 203, 206, 220 Aerobic Metabolism, 164, 165, 206 Aerobic Respiration, 164, 165, 206 Aerosol, 107, 165, 227 Affinity, 27, 165, 199, 219 Agar, 37, 43, 165, 180, 195, 210 Aggravation, 103, 165 Agonist, 165, 171, 173, 183, 186, 222 Airway, 37, 43, 56, 71, 165 Algorithms, 165, 172 Alimentary, 4, 49, 61, 165, 171, 185, 207, 208
Alkaline, 165, 166, 170, 173, 223 Alkaloid, 165, 174, 178, 202, 214, 223 Alkylating Agents, 102, 165 Alkylation, 93, 96, 102, 165 Alloys, 165, 206 Allylamine, 165, 166 Alopecia, 166, 180 Alpha-1, 166, 186 Alprostadil, 128, 166 Alternative medicine, 135, 166 Alveolar Process, 166, 216 Amber, 166, 195 Amebiasis, 166, 201 Amine, 121, 166, 193 Amiodarone, 127, 166 Ammonia, 100, 164, 166, 225 Amnestic, 166, 201 Amnion, 166, 176 Amoxicillin, 3, 48, 82, 166 Ampicillin, 7, 98, 106, 166 Ampulla, 166, 176, 185 Anaerobic, 32, 96, 166, 192, 194, 220 Anaesthesia, 51, 63, 167, 195 Anal, 150, 167, 188, 225 Analgesic, 163, 167, 185, 202, 205, 214 Analog, 32, 167, 177 Analogous, 11, 21, 167, 224 Anaphylatoxins, 167, 179 Anastomosis, 167, 189 Anatomical, 167, 176, 195 Anesthesia, 165, 167, 201 Anesthetics, 128, 167 Angina, 167, 208 Anginal, 167, 204 Animal Husbandry, 97, 112, 167 Anions, 28, 78, 167, 197, 222 Annealing, 167, 210 Anode, 167 Antagonism, 167, 223 Anthracycline, 163, 167, 181, 185, 194 Anthrax, 107, 167 Antianginal, 166, 167 Antiarrhythmic, 134, 166, 167 Antibody, 165, 168, 178, 192, 195, 196, 200, 219 Antiemetic, 127, 168, 169, 176, 183, 201 Antifungal, 19, 28, 101, 117, 128, 168 Antifungal Agents, 128, 168
230
Erythromycin
Antigen, 165, 168, 178, 190, 195, 196, 200 Antigen-Antibody Complex, 168, 178 Anti-infective, 8, 168, 176, 193, 197 Anti-Infective Agents, 8, 168 Anti-inflammatory, 6, 47, 127, 163, 168, 217 Antimetabolite, 168, 201 Antimicrobial, 7, 15, 31, 32, 38, 39, 44, 46, 48, 49, 52, 54, 56, 58, 60, 62, 63, 64, 65, 78, 79, 80, 103, 109, 122, 126, 128, 129, 168, 175, 177, 183, 201 Antineoplastic, 98, 106, 129, 163, 165, 168, 180, 183, 201, 202, 206, 209, 210, 227 Antineoplastic Agents, 98, 106, 165, 168, 209, 227 Antipsychotic, 168, 176, 204 Antipyretic, 163, 169, 214 Antiviral, 19, 98, 106, 127, 128, 163, 169, 196 Antiviral Agents, 98, 106, 128, 169 Anus, 150, 167, 169, 173, 178, 215 Anxiolytic, 169, 173, 201, 205 Apoptosis, 17, 169 Aqueous, 100, 120, 169, 170, 181, 184, 193 Archaea, 169, 201 Arginase, 98, 106, 169 Arginine, 98, 106, 167, 169, 204, 225 Aromatic, 169, 177 Arrhythmia, 167, 169, 227 Arterial, 165, 169, 194, 213, 222 Arteries, 169, 172, 180, 201, 210, 225 Arterioles, 169, 172, 226 Artery, 169, 180, 207, 214 Articular, 169, 199 Aseptic, 169, 205, 220 Asparaginase, 98, 106, 169 Aspartate, 169, 170 Assay, 16, 23, 37, 77, 170, 216 Astringent, 170, 221, 228 Atrial, 166, 170 Atrophy, 170, 186 Audiology, 129, 170 B Babesiosis, 170, 214 Bacillus, 107, 127, 167, 170, 173, 211 Bacteremia, 36, 47, 57, 170 Bacterial Infections, 27, 92, 99, 102, 104, 105, 109, 170, 198 Bacterial Physiology, 7, 164, 170 Bacterial Proteins, 7, 170 Bactericidal, 4, 33, 35, 42, 128, 170, 186 Bacteriostatic, 33, 128, 170, 186
Bacterium, 8, 11, 12, 14, 71, 73, 79, 99, 170, 179, 192, 205, 215, 224 Barium, 151, 170 Barotrauma, 129, 170 Base, 18, 19, 31, 40, 44, 71, 95, 138, 164, 170, 182, 186, 198, 210, 222 Behavioral Symptoms, 26, 170 Benign, 170, 203, 216 Benzene, 171, 197 Benzo(a)pyrene, 79, 171 Benzodiazepines, 12, 171, 173 Benzoyl Peroxide, 46, 65, 105, 130, 138, 171 Beta-Lactamases, 171, 194 Beta-Thromboglobulin, 171, 196 Bethanechol, 131, 136, 171 Bezoars, 151, 171 Bilateral, 171, 186, 211 Bile, 65, 171, 176, 189, 199, 212, 220, 222 Bile Acids, 171, 220, 222 Bile Acids and Salts, 171 Bile duct, 171, 176, 212 Biliary, 50, 78, 127, 171, 176 Bioavailability, 8, 10, 15, 17, 47, 72, 80, 111, 171 Biochemical, 9, 20, 30, 168, 171, 191, 218 Bioengineering, 26, 144, 171 Biological response modifier, 172, 196 Biological therapy, 172, 192 Biotechnology, 11, 31, 45, 79, 100, 135, 145, 172 Biotransformation, 172, 209 Bladder, 172, 179, 225, 226 Blastocyst, 172, 179, 184, 209 Bloating, 130, 151, 172, 190 Blood Coagulation, 172, 174, 177, 216 Blood Coagulation Factors, 172, 177 Blood Glucose, 80, 131, 151, 172, 194, 196 Blood Platelets, 172, 218 Blood pressure, 128, 172, 194, 202, 204, 211, 219 Blood vessel, 130, 172, 174, 175, 176, 180, 185, 192, 197, 200, 208, 219, 221, 223, 226 Blood-Brain Barrier, 172, 198, 222 Body Fluids, 172, 173, 183, 219 Bolus, 54, 172 Bolus infusion, 54, 172 Bone Marrow, 163, 164, 171, 172, 181, 186, 190, 199, 202, 212, 219 Bowel, 65, 167, 173, 182, 197, 198, 220 Bowel Movement, 173, 182, 220 Bradykinin, 173, 204
Index 231
Branch, 159, 173, 200, 207, 209, 214, 219, 223 Breakdown, 7, 173, 182, 189, 218 Breeding, 167, 173 Broad Ligament, 173, 187 Broad-spectrum, 118, 166, 173, 174, 175, 205 Bronchi, 173, 223, 224 Bronchial, 97, 112, 171, 173, 193, 223 Bronchial Spasm, 171, 173 Bronchiectasis, 66, 173 Bronchiseptica, 173, 208 Buccal, 103, 173 Burns, 127, 171, 173 Burns, Electric, 173 Buspirone, 10, 173 Bypass, 131, 173 C Calcitonin, 98, 106, 173 Calcium, 56, 71, 75, 127, 128, 173, 174, 178, 204, 207, 223, 227 Calcium channel blocker, 127, 128, 174, 227 Calcium Channel Blockers, 127, 128, 174 Calcium Hydroxide, 56, 174 Caloric intake, 27, 174 Campylobacter, 33, 35, 37, 39, 43, 48, 57, 65, 174 Capsaicin, 128, 174 Carbimazole, 64, 174 Carbohydrate, 174, 191, 218 Carbon Dioxide, 174, 188, 209 Carcinogen, 171, 174, 201 Carcinogenesis, 125, 174 Carcinogenic, 165, 171, 174, 196, 212, 220 Carcinoma, 174 Cardiac, 49, 163, 165, 167, 171, 174, 177, 184, 187, 189, 194, 201, 203, 214, 220 Cardiology, 87, 174 Cardiorespiratory, 174, 201 Cardiotoxicity, 174, 185 Cardiovascular, 71, 174, 218 Catalytic Domain, 9, 174 Catheter, 114, 174 Cations, 174, 197 Causal, 65, 174 Cefotaxime, 40, 174 Ceftazidime, 7, 175 Ceftriaxone, 63, 175 Cefuroxime, 49, 107, 175 Cell, 7, 11, 13, 15, 20, 24, 30, 35, 59, 71, 93, 163, 164, 165, 167, 169, 170, 172, 174,
175, 176, 177, 178, 179, 180, 181, 184, 185, 187, 189, 190, 191, 192, 193, 195, 196, 197, 198, 202, 204, 206, 210, 211, 213, 215, 217, 219, 222, 223, 224, 225, 226, 227 Cell Death, 169, 175, 187, 190 Cell Division, 170, 175, 187, 192, 202, 210, 217, 222 Cell membrane, 93, 174, 175, 211 Cell Respiration, 165, 175, 206 Cell Survival, 175, 192 Cellulitis, 126, 175 Central Nervous System, 134, 163, 171, 175, 176, 189, 198, 202, 218, 222, 223 Cephalexin, 4, 107, 175 Cephaloridine, 175 Cephalosporins, 4, 126, 128, 129, 171, 175 Cephalothin, 107, 175 Cerebrovascular, 174, 175 Cervical, 15, 18, 19, 150, 175, 217 Cervix, 150, 163, 175 Chemotactic Factors, 47, 175, 179 Chimeras, 11, 176 Chin, 32, 130, 176, 200 Chlorhexidine, 30, 176 Chlorpromazine, 127, 176 Cholangitis, 127, 176 Cholecystokinin, 26, 127, 176 Cholera, 48, 176, 227 Cholestasis, 127, 176 Cholesterol, 82, 87, 128, 171, 176, 199, 218, 220, 222 Cholinergic, 4, 168, 176 Chorioamnionitis, 15, 176 Chorion, 176 Chromatin, 169, 176 Chromosomal, 13, 176, 210 Chromosome, 11, 176, 179, 217 Chyme, 127, 176 Chymopapain, 176, 207 Chymotrypsin, 98, 106, 176 Cilastatin, 177, 194 Ciliary, 71, 177, 202 Cimetidine, 127, 177 Cinchona, 177, 214 Ciprofloxacin, 7, 35, 42, 43, 48, 65, 103, 127, 134, 177 Cirrhosis, 10, 177, 211, 212, 226 Cisplatin, 177, 205 Clear cell carcinoma, 177, 182 Clindamycin, 4, 32, 33, 36, 38, 39, 43, 44, 52, 64, 65, 126, 129, 130, 177
232
Erythromycin
Clinical Medicine, 177, 211 Clinical trial, 4, 16, 20, 24, 42, 63, 87, 88, 145, 177, 180, 181, 183, 203, 209, 213, 215 Clone, 31, 43, 45, 46, 70, 177 Cloning, 13, 41, 70, 72, 101, 172, 177 Cloxacillin, 40, 79, 177 Coagulants, 98, 107, 177 Cochlea, 177, 178, 196 Cochlear, 129, 178 Coenzyme, 14, 178, 199, 218 Cofactor, 178, 213 Colchicine, 93, 178 Collagen, 51, 166, 178, 188, 210, 212 Collapse, 173, 178 Colloidal, 178, 184, 187 Colon, 51, 94, 116, 178, 198 Combinatorial, 17, 21, 26, 97, 112, 115, 178 Comedo, 130, 178 Complement, 13, 167, 178, 179, 190 Complementary and alternative medicine, 77, 83, 179 Complementary medicine, 77, 179 Compliance, 111, 179 Computational Biology, 145, 179 Conception, 163, 179, 187, 211, 220 Concomitant, 64, 179 Condoms, 151, 179 Congenita, 179, 214 Congestion, 169, 179, 186 Conjugated, 171, 179, 181 Conjugation, 24, 97, 98, 106, 172, 179, 222 Conjunctiva, 179 Conjunctivitis, 36, 81, 150, 179 Connective Tissue, 173, 175, 178, 179, 188, 189, 199, 216 Consciousness, 167, 180, 183, 192 Constipation, 66, 128, 169, 180 Constriction, 180, 197 Consumption, 10, 27, 38, 41, 58, 62, 66, 180 Continuous infusion, 25, 180 Contraindications, ii, 180 Control group, 180, 209, 212 Controlled study, 53, 56, 59, 180 Coronary, 180, 201, 208 Coronary Thrombosis, 180, 201 Corpus, 180, 199, 208, 212 Corpus Luteum, 180, 199, 212 Cortex, 180, 206 Cortical, 180, 187 Corticosteroids, 130, 180 Crossing-over, 180, 215 Cryptosporidiosis, 170, 180
Crystallization, 113, 180 Culture Media, 165, 180 Curative, 180, 204, 223 Cutaneous, 35, 46, 55, 167, 180 Cyclic, 92, 118, 119, 120, 180, 192, 204, 213, 223, 227 Cyclophosphamide, 40, 79, 93, 180 Cyclosporine, 12, 16, 127, 181 Cytochrome, 10, 12, 16, 17, 34, 49, 50, 78, 87, 177, 181 Cytokine, 34, 36, 97, 112, 181, 196 Cytomegalovirus, 129, 181 Cytoplasm, 11, 169, 175, 181, 185, 202, 216 Cytostatic, 79, 181 Cytotoxic, 16, 29, 127, 174, 181, 195, 205 Cytotoxic chemotherapy, 181, 205 Cytotoxins, 17, 181 D Daunorubicin, 93, 98, 106, 163, 181, 183 Decidua, 181, 209 Decompression, 131, 181 Degenerative, 181, 192 Dehydration, 101, 117, 131, 176, 181 Deletion, 169, 181 Denaturation, 181, 210 Density, 20, 182, 199, 205 Dental Care, 182, 207 Dental Caries, 182, 188 Dentists, 126, 182 Dermatitis, 130, 182 DES, 53, 72, 167, 182 Deuterium, 182, 193 Diabetes Mellitus, 129, 130, 182, 191 Diagnostic procedure, 91, 135, 182 Diarrhea, 82, 94, 116, 166, 180, 182 Diastolic, 182, 194 Digestion, 94, 116, 128, 165, 171, 173, 176, 182, 184, 190, 197, 199, 208, 220 Digestive system, 89, 182, 189 Digestive tract, 110, 120, 182, 219 Dihydrotestosterone, 182, 215 Dilatation, 127, 163, 173, 182, 212 Dilate, 130, 182 Dilution, 37, 43, 182 Dimethyl, 93, 182 Direct, iii, 6, 35, 49, 137, 177, 182, 183, 190, 193, 214, 215 Disposition, 10, 16, 17, 25, 79, 182 Dissociation, 78, 165, 182 Dissociative Disorders, 182, 183 Distal, 183, 213 Diuresis, 183, 223
Index 233
Domperidone, 127, 131, 151, 183 Dopa, 127, 183, 198 Dopamine, 168, 176, 183, 198, 201, 204 Double-blind, 16, 35, 46, 48, 54, 59, 70, 183 Doxorubicin, 17, 93, 98, 106, 163, 183, 185 Doxycycline, 150, 183 Drug Interactions, 15, 17, 138, 183 Drug Resistance, 17, 54, 59, 60, 183 Drug Tolerance, 183, 223 Duct, 166, 183, 187, 206, 217, 220 Dumping Syndrome, 131, 183 Duodenal Ulcer, 183, 204 Duodenum, 130, 131, 171, 176, 183, 184, 185, 189, 197, 202, 206, 207, 220 Dura mater, 184, 200, 206 Dyspepsia, 20, 184 E Effector, 24, 163, 178, 184 Efficacy, 8, 16, 36, 38, 39, 40, 51, 63, 71, 73, 79, 94, 107, 173, 184, 194 Elastin, 178, 184 Electrolysis, 167, 174, 184 Electrolyte, 184, 211, 219 Electrophoresis, 54, 184, 195 Embryo, 163, 166, 172, 184, 195, 211, 220, 225 Embryo Transfer, 184, 211 Emetic, 184, 228 Empiric, 25, 44, 184 Empirical, 100, 184 Emulsion, 184, 188 Endemic, 11, 176, 184 Endocarditis, 60, 128, 184 Endocardium, 184 Endogenous, 14, 94, 98, 107, 116, 172, 177, 183, 184, 185, 189, 205 Endometrium, 181, 185, 200 Endorphin, 185, 189 Endoscopic, 185, 201 Endoscopy, 53, 151, 185 Endothelial cell, 52, 172, 184, 185, 196 Endothelium, 185, 204 Endothelium-derived, 185, 204 Endotoxins, 178, 185, 198 Enkephalins, 98, 106, 185, 204, 205 Enteral Nutrition, 52, 134, 136, 185 Enteropeptidase, 185, 225 Environmental Health, 144, 146, 185 Enzymatic, 10, 85, 98, 106, 166, 174, 178, 182, 185, 193, 207, 210 Epidemic, 11, 185 Epidural, 60, 185
Epirubicin, 93, 185 Epithelial, 54, 71, 97, 112, 164, 181, 185 Epithelial Cells, 54, 71, 97, 112, 185 Epithelium, 71, 185, 189 Erectile, 186, 208 Erection, 128, 186 Ergot, 186 Ergotamine, 72, 186 Erythema, 64, 186 Erythema Nodosum, 64, 186 Erythromycin Estolate, 186 Erythromycin Ethylsuccinate, 35, 41, 42, 150, 186 Erythropoietin, 98, 106, 186 Escalation, 24, 186 Esophageal, 133, 186 Esophagectomy, 57, 186 Esophagus, 182, 186, 189, 215, 220, 226 Estrogen, 21, 186, 212, 217, 222 Ethanol, 186, 187 Ether, 120, 169, 187 Etoposide, 17, 40, 79, 187 Eustachian tube, 170, 187 Evacuation, 180, 187, 189, 198 Excitability, 187, 203, 214 Excitation, 5, 187, 204 Excitatory, 26, 187 Exocrine, 176, 187, 206 Exogenous, 14, 164, 172, 177, 184, 187, 222 Extender, 101, 117, 187 Extracellular, 179, 187, 188, 219, 223 Extraction, 15, 187 Eye Infections, 164, 187 F Facial, 106, 187, 207 Fallopian tube, 150, 187 Family Planning, 145, 187 Fat, 171, 173, 187, 199, 216, 217, 225 Feces, 180, 187, 220 Fermentation, 8, 14, 20, 21, 93, 187 Fertilization in Vitro, 187, 211 Fetal Blood, 176, 187 Fetus, 129, 163, 176, 186, 187, 209, 211, 220, 225, 226 Fibrin, 114, 172, 188, 223 Fibrinogen, 188, 223 Fibroblasts, 36, 188, 196 Fibrosis, 66, 93, 127, 165, 188, 217 Filtration, 5, 188 Fistula, 188, 189 Fixation, 114, 188 Fluorescence, 13, 188
234
Erythromycin
Fluorine, 109, 188 Fold, 12, 14, 20, 173, 188 Follicles, 106, 188 Foramen, 176, 188 Forearm, 172, 188 Fovea, 188 Free Radicals, 182, 188 Fructose, 188, 191 Fungi, 115, 168, 179, 187, 189, 201, 227, 228 Fungicides, Industrial, 168, 189 Fungus, 175, 186, 189 G Gallate, 77, 189 Gallbladder, 163, 171, 176, 182, 189 Gamma-Endorphin, 189 Ganglia, 163, 169, 189, 204, 208 Gas, 166, 174, 188, 189, 193, 203, 204, 216, 221, 227 Gastric Bypass, 65, 189 Gastric Emptying, 4, 20, 26, 52, 54, 58, 60, 61, 66, 70, 80, 94, 116, 127, 130, 131, 189, 190 Gastric Juices, 189, 208 Gastric Mucosa, 189, 208 Gastric Outlet Obstruction, 131, 189 Gastric Resection, 131, 189 Gastrin, 177, 189, 193 Gastroduodenal, 50, 53, 127, 131, 189 Gastroenterology, 21, 50, 53, 54, 56, 61, 80, 94, 116, 126, 127, 130, 189 Gastrointestinal tract, 103, 130, 186, 190, 218, 219 Gastroparesis, 20, 61, 128, 130, 151, 190 Gastrostomy, 185, 190 Gels, 46, 190 Gene Expression, 190, 219, 225 Gene Therapy, 164, 190 Genetic Engineering, 11, 101, 117, 172, 177, 190 Genetic testing, 190, 210 Genetics, 18, 100, 101, 164, 179, 190, 209 Genital, 177, 190, 201, 216, 226 Genitourinary, 190, 225, 226 Genotype, 23, 62, 190, 209 Gestation, 51, 190, 208, 209, 220 Giant Cells, 190, 217 Giardiasis, 190, 201 Gland, 130, 164, 190, 199, 206, 207, 212, 217, 220, 223 Glottis, 190, 193, 209 Glucose, 21, 30, 131, 172, 182, 191, 196, 217 Glucose Intolerance, 182, 191
Glucose tolerance, 21, 191 Glucose Tolerance Test, 191 Glycine, 166, 171, 191, 204, 218 Glycoprotein, 16, 49, 79, 186, 188, 190, 191, 202, 209 Glycoside, 28, 191, 217 Glycosylation, 41, 191 Gonadal, 191, 220 Gonadotropin, 21, 92, 127, 191 Gonorrhea, 29, 175, 191 Gout, 178, 191 Governing Board, 191, 211 Graft, 191, 193 Gram-Negative Bacteria, 31, 96, 118, 191, 225 Gram-positive, 39, 96, 118, 119, 120, 175, 191, 194, 203, 205, 220, 221, 227 Gram-Positive Bacteria, 42, 96, 192, 205 Granule, 192, 216 Granuloma, 129, 192 Growth factors, 114, 192 Guanylate Cyclase, 192, 204 H Habitat, 192, 203, 204 Haemophilus, 36, 45, 78, 175, 192 Hair follicles, 130, 192, 220 Half-Life, 175, 192 Haptens, 165, 192 Heart attack, 87, 192 Helicobacter, 37, 41, 44, 57, 77, 192 Heme, 181, 192 Hemolytic, 47, 192, 195 Hemorrhage, 192, 221 Hemostasis, 192, 218 Hepatic, 10, 12, 15, 25, 50, 87, 127, 191, 192, 218 Hepatic Encephalopathy, 10, 192 Hepatitis, 10, 127, 192, 208 Hepatocellular, 127, 192, 193 Hepatocellular carcinoma, 127, 193 Hepatocyte, 176, 193 Hepatotoxicity, 80, 193 Hereditary, 129, 191, 193 Heredity, 163, 190, 193 Heterogeneity, 42, 165, 193 Heterotrophic, 189, 193 Hiccup, 176, 193 Histamine, 167, 168, 177, 193, 204, 215 Hormone, 92, 94, 116, 127, 173, 180, 182, 186, 189, 193, 196, 197, 212, 218, 219, 222, 223
Index 235
Host, 11, 14, 21, 23, 97, 101, 112, 115, 117, 126, 170, 193, 226, 227 Hybrid, 9, 26, 177, 193 Hybridomas, 193, 196 Hydration, 131, 193 Hydrogen, 27, 92, 96, 109, 116, 119, 120, 163, 166, 170, 174, 181, 182, 193, 202, 206, 213, 222 Hydrogen Peroxide, 193, 222 Hydrogenation, 171, 193 Hydrolysis, 164, 169, 171, 172, 177, 193, 213, 225 Hydrophilic, 97, 106, 193 Hydroxylysine, 178, 193 Hydroxyproline, 166, 178, 194 Hypertension, 10, 174, 194, 211 Hyperthermia, 127, 194 Hypnotic, 194, 201 Hypoglycemic, 127, 194 Hypoglycemic Agents, 127, 194 Hypotension, 169, 171, 194 Hypothalamic, 92, 98, 106, 194, 219 Hypothalamus, 194, 212, 219 Hypothermia, 127, 194 Hypothyroidism, 129, 194 Hypoxia, 134, 194 Hypoxic, 194, 201 I Id, 74, 81, 152, 158, 160, 194 Idarubicin, 93, 194 Idiopathic, 129, 130, 194, 217 Imidazole, 174, 193, 194, 215 Imipenem, 7, 177, 194 Immune function, 194, 195 Immune response, 168, 192, 194, 195, 221, 226, 227 Immune system, 172, 194, 195, 200, 226, 227 Immunity, 181, 195 Immunodeficiency, 27, 34, 111, 195, 222 Immunodeficiency syndrome, 195, 222 Immunodiffusion, 165, 195 Immunoelectrophoresis, 165, 195 Immunologic, 129, 175, 195 Immunology, 11, 12, 24, 52, 70, 165, 195 Immunosuppressant, 101, 117, 165, 195, 201 Immunosuppressive, 19, 180, 195 Immunosuppressive Agents, 19, 195 Impairment, 88, 170, 176, 187, 195, 200 Impetigo, 35, 42, 195 Impotence, 128, 186, 195
In vivo, 10, 12, 13, 15, 16, 20, 38, 39, 56, 98, 106, 190, 195 Incision, 195, 197 Incubation, 195, 208 Incubation period, 195, 208 Indicative, 125, 195, 207, 226 Induction, 16, 24, 39, 77, 168, 195, 212, 218 Infarction, 171, 180, 195, 201, 210 Infusion, 25, 72, 103, 196, 224 Ingestion, 167, 191, 196, 210, 223 Inhalation, 165, 193, 196, 210 Initiation, 196, 205, 216, 221 Inner ear, 129, 175, 196, 198, 226 Inorganic, 120, 177, 196, 203, 209 Insight, 100, 196 Insomnia, 196, 225 Insulin, 25, 97, 106, 128, 151, 191, 196, 216 Insulin-dependent diabetes mellitus, 196 Interferon, 98, 106, 196 Interferon-alpha, 196 Interindividual, 12, 196 Interleukin-6, 34, 62, 196 Interleukin-8, 43, 196 Interleukins, 195, 197 Internal Medicine, 25, 70, 71, 72, 189, 197 Intervertebral, 114, 197 Intestinal, 10, 12, 15, 16, 17, 20, 24, 51, 94, 116, 174, 176, 180, 185, 191, 192, 197 Intestinal Mucosa, 15, 176, 197 Intestine, 12, 71, 171, 173, 197, 198, 208, 214, 221 Intoxication, 72, 197 Intracellular, 11, 15, 24, 34, 71, 174, 196, 197, 204, 211, 213, 215, 216 Intrahepatic, 10, 197 Intramuscular, 103, 197, 207 Intramuscular injection, 103, 197 Intravenous, 4, 54, 59, 65, 72, 103, 131, 151, 196, 197, 207 Intrinsic, 12, 22, 29, 165, 197 Invasive, 20, 103, 195, 197 Iodine, 134, 197, 201 Ions, 93, 163, 170, 182, 184, 193, 197, 202 Ischemia, 72, 170, 197 Isoflavones, 73, 79, 197 Isoniazid, 127, 197 Isopropyl, 110, 197 Isotretinoin, 130, 197 J Jejunostomy, 185, 197 Jejunum, 189, 197 Joint, 169, 177, 197, 222
236
Erythromycin
K Kanamycin, 13, 197 Kb, 32, 144, 198 Keratin, 178, 198, 217 Keratinocytes, 196, 198 Keto, 101, 105, 117, 198 Kidney Disease, 88, 89, 128, 144, 151, 198 L Labile, 178, 198 Labyrinth, 177, 196, 198, 206, 217, 227 Labyrinthitis, 129, 198 Lactation, 198, 212 Lag, 4, 198 Large Intestine, 182, 197, 198, 215, 219 Laxative, 165, 198 Lethal, 170, 198 Lethargy, 194, 198 Leukemia, 40, 79, 183, 185, 190, 198 Leukocytes, 173, 175, 196, 197, 198, 202 Levodopa, 183, 198 Levofloxacin, 33, 42, 46, 198 Library Services, 158, 198 Life cycle, 189, 199 Ligaments, 114, 180, 199 Ligands, 27, 94, 116, 199 Lincomycin, 177, 199 Lipid, 122, 196, 198, 199, 201 Lipophilic, 97, 106, 199 Lipopolysaccharide, 191, 199 Lipoprotein, 191, 199 Liver cancer, 127, 199 Liver Neoplasms, 199, 227 Localization, 12, 199 Localized, 103, 163, 182, 188, 196, 199, 206, 210, 225 Loop, 129, 189, 199, 206 Lovastatin, 199, 218 Lutein Cells, 199, 212 Lymph, 175, 185, 199, 217 Lymph node, 175, 199, 217 Lymphatic, 185, 196, 199, 217, 219, 220 Lymphatic system, 199, 217, 219, 220 Lymphocyte, 168, 200 Lymphoid, 180, 200, 224 Lysine, 93, 193, 200, 225 Lytic, 27, 200 M Macrolides, 13, 21, 22, 34, 35, 39, 41, 62, 82, 95, 97, 98, 99, 104, 108, 109, 112, 200 Malignancy, 129, 200 Malignant, 164, 168, 199, 200, 203 Mammary, 200, 222
Mandible, 166, 176, 200, 216 Manometry, 131, 151, 200 Mastoiditis, 62, 200 Mediate, 9, 49, 183, 200, 215 Mediator, 25, 176, 183, 200, 218 MEDLINE, 145, 200 Membrane, 16, 122, 166, 175, 176, 178, 179, 187, 191, 200, 202, 205, 206, 211, 214, 224 Meninges, 175, 184, 200 Meningitis, 129, 200 Menstrual Cycle, 21, 200, 212 Menstruation, 181, 200 Mental, iv, 4, 89, 144, 146, 176, 182, 194, 200, 214 Mental Disorders, 89, 200, 214 Mental Health, iv, 4, 89, 144, 146, 200, 214 Mental Processes, 182, 200, 214 Metabolic disorder, 129, 191, 201 Metabolite, 6, 9, 15, 39, 44, 172, 182, 199, 201, 212 Methimazole, 64, 174, 201 Methionine, 182, 201, 212, 222 Methotrexate, 127, 201 Methyltransferase, 41, 201 Metoclopramide, 127, 128, 131, 136, 151, 201 Metronidazole, 4, 16, 30, 39, 63, 126, 129, 201 MI, 15, 41, 103, 105, 161, 201 Microbe, 201, 224 Microbiological, 23, 201 Microorganism, 178, 201, 207, 227 Micro-organism, 182, 201, 209 Microscopy, 49, 201, 205 Microtubules, 201, 206 Midazolam, 10, 12, 15, 16, 201 Mineralization, 174, 201 Miocamycin, 64, 201 Miscarriage, 150, 201 Miscible, 100, 202 Mitosis, 169, 202, 219 Mitotic, 187, 202, 222, 227 Mitoxantrone, 17, 202 Modeling, 62, 202 Modification, 4, 6, 9, 27, 166, 190, 202 Molecular Structure, 202, 225 Monitor, 202, 205 Monocytes, 196, 198, 202 Mononuclear, 192, 202 Morphine, 202, 203, 205 Morphological, 8, 184, 189, 202 Morphology, 51, 169, 202
Index 237
Motilin, 23, 70, 71, 94, 116, 131, 202 Motility, 20, 35, 60, 65, 67, 70, 71, 127, 130, 133, 136, 202, 218 Motion Sickness, 202, 203 Motor Activity, 57, 202 Mucociliary, 61, 66, 202, 218 Mucolytic, 94, 163, 202 Mucosa, 15, 189, 202, 212 Mucus, 150, 202 Multicenter study, 63, 203 Multidrug resistance, 16, 79, 203, 209 Mupirocin, 35, 42, 203 Musculature, 131, 203 Mutagen, 171, 203 Mutagenic, 8, 165, 203 Mycobacterium, 34, 78, 170, 203, 225 Myocardium, 201, 203 Myotonia, 203, 214 N Narcosis, 203 Narcotic, 128, 202, 203 Nasogastric, 131, 185, 203 Nausea, 21, 94, 116, 130, 151, 168, 190, 203, 205 NCI, 1, 88, 143, 203 Need, 3, 8, 95, 109, 115, 126, 135, 153, 164, 203, 223 Neomycin, 22, 27, 51, 83, 203 Neonatal, 15, 18, 19, 30, 36, 134, 150, 203 Neoplasm, 203, 225 Nephropathy, 198, 203 Nerve, 164, 167, 176, 190, 200, 203, 204, 206, 207, 220, 224 Nervous System, 127, 175, 200, 203, 204, 208 Neuroleptic, 168, 204, 205 Neuromuscular, 131, 163, 204, 211 Neurons, 187, 189, 198, 204 Neuropathy, 72, 128, 204, 208 Neurotransmitter, 163, 164, 166, 173, 183, 191, 193, 204, 219, 221 Neutrophil, 35, 59, 72, 97, 112, 204 Niacin, 127, 204, 225 Niche, 11, 204 Nifedipine, 12, 204 Nitric Oxide, 61, 204 Nitrogen, 96, 105, 109, 110, 114, 119, 165, 166, 180, 188, 204, 225 Nizatidine, 51, 204 Nosocomial, 24, 204 Novobiocin, 122, 204 Nuclear, 28, 61, 72, 179, 204
Nuclei, 179, 190, 202, 205, 213, 217 Nucleic acid, 204, 205 Nucleolus, 205, 216 Nucleus, 169, 176, 180, 181, 182, 202, 205, 213, 221 O Ofloxacin, 40, 42, 70, 79, 150, 205 Oleandomycin, 29, 37, 47, 98, 106, 205 Oncology, 24, 127, 205 Ondansetron, 4, 205 Opacity, 182, 205 Ophthalmic, 36, 138, 205 Ophthalmology, 188, 205 Opiate, 127, 202, 205 Opioid Peptides, 185, 205 Opium, 202, 205 Organ Culture, 205, 223 Organelles, 181, 202, 205 Ori region, 205, 215 Orofacial, 126, 205 Oropharynx, 205, 225 Ossicles, 206 Osteoclasts, 173, 206 Osteomyelitis, 126, 206 Otosclerosis, 129, 206 Outpatient, 131, 206 Ovulation, 92, 206 Ovum, 180, 181, 190, 199, 206, 212, 228 Oxacillin, 177, 206 Oxazolidinones, 7, 206 Oxidation, 25, 163, 172, 181, 201, 206 Oxidative metabolism, 23, 164, 165, 206 P Pachymeningitis, 200, 206 Paclitaxel, 17, 24, 206 Palladium, 102, 108, 206 Palliative, 206, 223 Pancreas, 163, 176, 182, 189, 196, 206, 219, 225 Pancreatic, 176, 185, 206 Pancreatic cancer, 185, 206 Pancreatic Juice, 176, 206 Pancreaticoduodenectomy, 60, 206 Papain, 98, 106, 207 Paranasal Sinuses, 207, 218 Parasite, 72, 207, 225 Parasitic, 11, 180, 207, 216, 225 Parathyroid, 98, 106, 207, 223 Parathyroid Glands, 207 Parathyroid hormone, 98, 106, 207 Parenteral, 98, 106, 136, 207 Parotid, 207, 217
238
Erythromycin
Paroxysmal, 207, 208, 228 Parturition, 207, 212 Pathogen, 111, 195, 207 Pathologic, 127, 169, 180, 207, 213, 216 Pathologic Processes, 169, 207 Pathologies, 127, 207 Pathophysiology, 25, 26, 131, 207 Patient Education, 150, 156, 158, 161, 207 Pediatric Dentistry, 128, 207 Pelvic, 150, 207 Pelvic inflammatory disease, 150, 207 Pelvis, 163, 173, 207, 226 Penicillin, 3, 33, 35, 38, 39, 40, 43, 44, 56, 58, 59, 62, 83, 126, 134, 166, 167, 208 Penicillin Resistance, 38, 58, 208 Penis, 150, 179, 208, 209 Pepsin, 177, 208 Pepsin A, 177, 208 Peptic, 130, 189, 208 Peptic Ulcer, 130, 189, 208 Peptide, 9, 24, 27, 94, 116, 166, 173, 176, 177, 185, 189, 198, 205, 208, 212, 213, 219, 223 Peptide Chain Elongation, 177, 208 Perfusion, 194, 208 Perhexiline, 127, 208 Pericoronitis, 126, 208 Perinatal, 18, 19, 29, 208 Perioral, 130, 208 Peripheral blood, 166, 196, 208 Peripheral Nervous System, 185, 204, 208, 219, 221 Peristalsis, 183, 208 Pernicious, 11, 208 Peroxide, 65, 171, 208 Pertussis, 32, 33, 38, 39, 47, 51, 58, 66, 134, 208, 228 P-Glycoprotein, 10, 209 Phallic, 188, 209 Pharmacogenetics, 24, 209 Pharmacokinetic, 15, 17, 24, 41, 62, 119, 209 Pharmacologic, 16, 23, 131, 167, 192, 209, 224, 226 Pharyngitis, 61, 82, 209, 217 Phenotype, 7, 23, 33, 40, 47, 59, 64, 209 Phenyl, 96, 209 Pheromone, 24, 209 Phosphates, 209 Phosphoric Acids, 110, 209 Phosphorus, 127, 174, 207, 209 Phosphorylated, 25, 178, 209
Physiologic, 165, 183, 192, 200, 209, 212, 215, 216 Physiology, 25, 51, 71, 131, 174, 189, 209 Pigmentation, 8, 209 Pigments, 33, 209 Placebos, 30, 209 Placenta, 129, 187, 209, 212, 225 Plants, 165, 173, 174, 181, 191, 202, 209, 210, 217, 224 Plaque, 176, 210 Plasma, 34, 42, 80, 94, 111, 114, 116, 171, 173, 175, 187, 188, 191, 192, 210 Plasmid, 8, 13, 24, 41, 70, 72, 73, 79, 210, 226 Platelet Aggregation, 166, 167, 204, 210 Platelets, 171, 204, 210 Platinum, 177, 199, 206, 210 Pneumonia, 43, 48, 49, 63, 150, 180, 210 Podophyllotoxin, 187, 210 Point Mutation, 31, 45, 210 Poisoning, 186, 197, 203, 210 Polyarteritis Nodosa, 129, 210 Polyarthritis, 93, 210 Polymerase, 71, 169, 210 Polymerase Chain Reaction, 71, 210 Polymorphic, 122, 211 Polymyxin, 122, 211 Portal Hypertension, 10, 211 Portal Vein, 211 Portosystemic Shunt, 10, 211 Posterior, 167, 206, 211 Postoperative, 50, 64, 211 Postprandial, 21, 26, 130, 211 Post-translational, 14, 211 Potassium, 211, 214 Potentiate, 7, 211 Practice Guidelines, 130, 146, 211 Preclinical, 17, 23, 211 Precursor, 7, 14, 20, 23, 180, 183, 184, 185, 189, 198, 211, 212, 225 Pregnancy Outcome, 29, 211 Prenatal, 30, 184, 211 Preoperative, 51, 211 Presbycusis, 129, 211 Prevalence, 29, 35, 38, 42, 57, 59, 63, 64, 211 Primary Biliary Cirrhosis, 134, 212 Primary endpoint, 30, 212 Probe, 16, 23, 26, 212 Prodrug, 212 Progeny, 179, 212 Progesterone, 21, 212, 220
Index 239
Progressive, 177, 183, 186, 192, 211, 212, 225 Prokinetic Drugs, 127, 136, 212 Prolactin, 98, 106, 183, 212 Proline, 178, 194, 212 Promoter, 212, 227 Promyelocytic leukemia, 212, 225 Pro-Opiomelanocortin, 189, 205, 212 Prophylaxis, 36, 61, 126, 128, 134, 169, 212, 216, 226 Prostaglandin, 212 Protease, 27, 213 Protective Agents, 174, 213 Protein S, 5, 25, 27, 35, 61, 78, 169, 172, 177, 186, 203, 213, 216, 221, 223 Proteolytic, 166, 178, 185, 188, 207, 213 Protocol, 11, 13, 17, 20, 209, 213 Protons, 193, 213, 215 Proto-Oncogene Proteins, 206, 213 Proto-Oncogene Proteins c-mos, 206, 213 Protozoa, 98, 99, 118, 179, 201, 213 Proximal, 65, 183, 189, 213 Psoriasis, 213, 216, 225 Psychiatric, 88, 200, 213 Psychiatry, 26, 188, 213, 221 Psychic, 200, 214 Psychology, 182, 214 Puberty, 106, 214 Public Health, 21, 66, 146, 171, 214 Public Policy, 145, 214 Pulmonary, 172, 180, 214, 216, 226 Pulmonary Artery, 172, 214, 226 Pulse, 5, 25, 202, 214 Purifying, 113, 214 Purulent, 214, 226 Pustular, 163, 195, 214 Pyloric Sphincter, 21, 214 Pyloric Stenosis, 55, 65, 67, 82, 134, 214 Pylorus, 60, 131, 183, 214 Pyogenic, 206, 214 Q Quinidine, 83, 98, 106, 127, 177, 214 Quinine, 127, 177, 214 R Race, 114, 183, 214 Racemic, 183, 214 Radiation, 188, 194, 201, 215, 228 Radioactive, 14, 22, 192, 193, 205, 215 Radioisotope, 151, 215 Randomized, 16, 18, 19, 25, 30, 42, 46, 48, 51, 53, 54, 56, 59, 61, 63, 65, 184, 215 Ranitidine, 127, 215
Reaction Time, 108, 215 Reactive Oxygen Species, 47, 215 Reagent, 93, 215 Receptor, 23, 24, 94, 116, 127, 128, 164, 168, 173, 183, 204, 205, 215, 218 Receptors, Serotonin, 215, 218 Recombinant, 11, 20, 97, 98, 101, 107, 112, 117, 215, 226 Recombination, 17, 179, 190, 215 Rectal, 103, 215 Rectum, 169, 173, 178, 182, 189, 198, 215 Red blood cells, 192, 215, 217, 219 Reductase, 27, 199, 201, 215, 218 Refer, 1, 5, 173, 178, 188, 189, 199, 204, 215, 224 Reflux, 23, 50, 215 Refraction, 215, 219 Regimen, 87, 111, 150, 184, 215 Reliability, 5, 18, 215 Replication Origin, 70, 215 Replicon, 24, 216 Reproduction Techniques, 211, 216 Resection, 131, 216 Resorption, 25, 206, 216 Respiratory System, 202, 216 Retinoids, 127, 216 Retrospective, 78, 216 Rheology, 66, 216 Rheumatism, 216 Rheumatoid, 93, 216 Rhinovirus, 54, 216 Ribonuclease, 12, 98, 106, 216 Ribose, 164, 216 Ribosome, 5, 7, 22, 27, 216, 224 Rickettsiae, 11, 216 Ristocetin, 216, 226 Rod, 170, 192, 216 Rosiglitazone, 24, 216 Roxithromycin, 32, 33, 35, 38, 39, 43, 44, 70, 79, 94, 95, 97, 112, 216 Rubella, 129, 216 Ruminants, 103, 217 S Salicylate, 217 Salicylic, 217 Salicylic Acids, 217 Salivary, 181, 182, 206, 217 Salivary glands, 181, 182, 217 Saponins, 217, 220 Sarcoidosis, 129, 217 Scalpel, 130, 217 Scarlet Fever, 62, 217
240
Erythromycin
Screening, 8, 16, 17, 99, 177, 217 Sebaceous, 106, 130, 217 Sebaceous gland, 106, 130, 217 Sebum, 130, 163, 178, 217 Secretion, 25, 35, 92, 163, 177, 193, 194, 196, 197, 198, 202, 204, 215, 217 Secretory, 131, 217 Sedative, 201, 217 Segregation, 215, 217 Selective estrogen receptor modulator, 217, 222 Semicircular canal, 196, 217 Semisynthetic, 44, 166, 174, 175, 177, 187, 194, 216, 217 Senile, 211, 218 Sepsis, 15, 218 Septic, 39, 169, 218 Sequence Analysis, 8, 218 Sequencing, 210, 218 Serine, 176, 213, 218, 225 Serotonin, 4, 168, 173, 204, 205, 215, 218, 225 Serum, 25, 29, 134, 166, 167, 178, 191, 218 Sex Characteristics, 214, 218, 222 Shock, 218, 225 Side effect, 106, 111, 126, 129, 130, 137, 164, 169, 172, 180, 218, 224 Signs and Symptoms, 210, 218 Silanes, 121, 218 Silicon, 218 Simvastatin, 134, 218 Sinusitis, 61, 150, 218 Skeletal, 214, 218 Skull, 219, 222 Sludge, 127, 219 Small intestine, 35, 176, 183, 184, 189, 190, 193, 197, 203, 214, 219, 225 Smooth muscle, 49, 94, 116, 165, 167, 171, 173, 174, 193, 202, 219, 221 Sneezing, 208, 219 Sodium, 127, 191, 214, 219 Solid tumor, 183, 219 Solvent, 19, 100, 110, 120, 171, 186, 219 Somatostatin, 98, 106, 131, 219 Somatotropin, 98, 106, 219 Spasmodic, 173, 209, 219 Specialist, 152, 219 Specificity, 9, 165, 219 Spectrophotometry, 100, 219 Spectrum, 5, 6, 35, 96, 126, 194, 201, 216, 219 Sperm, 176, 219
Spermatogenesis, 92, 219 Spinal cord, 175, 176, 184, 185, 200, 204, 206, 208, 220 Spiramycin, 34, 78, 220 Spirochete, 220, 222 Spleen, 181, 199, 217, 220 Spontaneous Abortion, 211, 220 Sputum, 66, 220 Staphylococcus, 7, 33, 35, 41, 44, 59, 64, 178, 195, 220 Staphylococcus aureus, 7, 33, 35, 41, 44, 59, 64, 195, 220 Statistically significant, 111, 220 Stem Cells, 186, 220 Stenosis, 134, 220, 221 Sterile, 114, 169, 207, 220 Sterility, 150, 181, 220 Steroid, 18, 122, 171, 217, 218, 220 Stillbirth, 30, 150, 211, 220 Stimulant, 193, 220, 222 Stimulus, 187, 196, 198, 215, 220, 223 Stomach, 4, 50, 94, 103, 116, 127, 128, 130, 131, 151, 163, 170, 176, 182, 186, 189, 190, 191, 193, 203, 208, 214, 215, 217, 219, 220 Stool, 178, 198, 220 Strand, 210, 221 Streptococcal, 37, 55, 61, 199, 221 Streptococci, 4, 31, 34, 36, 42, 47, 55, 56, 59, 63, 134, 195, 203, 217, 221 Streptomycin, 72, 221 Stress, 129, 203, 221 Stricture, 220, 221 Stroke, 89, 144, 221 Structure-Activity Relationship, 21, 221 Stupor, 198, 203, 221 Styptic, 221, 228 Subacute, 196, 218, 221 Subclinical, 196, 221 Subcutaneous, 25, 103, 175, 207, 221 Subspecies, 219, 221 Substance P, 186, 201, 205, 216, 217, 221 Substrate, 9, 10, 12, 13, 15, 17, 20, 26, 174, 221 Substrate Specificity, 9, 13, 221 Suction, 188, 221 Sulfadiazine, 52, 222 Sulfotransferases, 10, 222 Sulfur, 130, 201, 222 Superoxide, 40, 98, 106, 222 Superoxide Dismutase, 98, 106, 222 Symphysis, 176, 222
Index 241
Symptomatic, 61, 127, 222 Synergistic, 8, 212, 222 Syphilis, 129, 222 Systemic, 15, 16, 39, 78, 80, 98, 103, 106, 107, 127, 131, 134, 138, 172, 196, 217, 222, 226 Systolic, 194, 222 T Tachycardia, 170, 222, 224 Tachypnea, 170, 222 Tacrine, 127, 222 Talcum, 114, 222 Talcum powder, 114, 222 Tamoxifen, 127, 217, 222 Taxanes, 17, 222 Teichoic Acids, 192, 222 Temporal, 129, 200, 222 Teratogenic, 165, 197, 222, 225 Testosterone, 215, 222 Tetany, 207, 222 Tetracycline, 7, 22, 24, 38, 39, 42, 43, 47, 56, 62, 64, 65, 72, 114, 126, 129, 183, 223 Tetravalent, 218, 223 Theophylline, 73, 223 Therapeutics, 4, 23, 27, 46, 49, 50, 61, 63, 139, 223 Thermal, 182, 210, 223 Thorax, 163, 223 Threshold, 187, 194, 223 Thrombin, 188, 210, 223 Thrombosis, 87, 171, 213, 221, 223 Thyroid, 98, 106, 127, 173, 194, 197, 201, 207, 223 Thyroid Gland, 207, 223 Thyroid Hormones, 201, 223 Thyrotropin, 194, 223 Tissue Culture, 44, 223 Tolerance, 45, 104, 191, 223 Tone, 171, 223 Tonsillitis, 61, 217, 223 Tonsils, 223, 224 Tooth Preparation, 164, 224 Topical, 35, 42, 46, 47, 70, 71, 103, 106, 130, 138, 170, 176, 186, 193, 197, 207, 224, 225 Torsades de Pointes, 63, 64, 224 Toxic, iv, 23, 127, 165, 171, 177, 179, 181, 195, 204, 210, 224, 226 Toxicity, 8, 23, 44, 49, 163, 174, 183, 194, 204, 216, 224, 227 Toxicology, 17, 65, 78, 125, 146, 224 Toxin, 21, 223, 224 Toxoplasmosis, 129, 170, 222, 224
Trace element, 188, 218, 224 Trachea, 173, 223, 224 Transcriptase, 111, 224 Transfection, 172, 190, 224 Transferases, 191, 224 Transfusion, 187, 224 Translation, 166, 186, 203, 224 Translational, 7, 224 Translocation, 177, 186, 224 Transmitter, 163, 183, 200, 224 Trauma, 54, 103, 129, 225, 228 Tretinoin, 46, 71, 225 Triazolam, 12, 225 Trichomoniasis, 201, 225 Tricyclic, 109, 118, 128, 225 Troglitazone, 127, 225 Trypsin, 98, 106, 177, 185, 225, 228 Tryptophan, 178, 218, 225 Tuberculostatic, 197, 225 Tumour, 62, 225 Tunica, 202, 225 Tylosin, 9, 21, 72, 225 U Ulcer, 175, 183, 208, 225 Umbilical Cord, 176, 225 Unconscious, 167, 194, 225 Urea, 169, 225 Ureaplasma, 37, 56, 64, 225 Ureaplasma urealyticum, 37, 56, 64, 225 Urethra, 150, 208, 225, 226 Urinary, 171, 175, 177, 190, 225, 226 Urinary Retention, 171, 226 Urinary tract, 175, 226 Urine, 150, 172, 183, 225, 226 Urogenital, 190, 191, 225, 226 Uterus, 163, 173, 175, 180, 181, 185, 200, 212, 226 V Vaccination, 107, 226 Vaccine, 213, 226 Vagina, 29, 175, 182, 200, 226 Vaginal, 16, 29, 150, 226 Vaginitis, 129, 226 Vancomycin, 45, 98, 106, 107, 129, 226 Varices, 10, 226 Vascular, 127, 165, 166, 174, 185, 195, 196, 204, 209, 223, 226 Vascular Resistance, 166, 226 Vasculitis, 210, 226 Vasodilator, 166, 173, 183, 193, 204, 208, 226 Vector, 11, 13, 226
242
Erythromycin
Vein, 197, 205, 207, 211, 225, 226 Venereal, 222, 226 Venoms, 181, 226 Venous, 171, 213, 226 Ventricle, 194, 214, 222, 226 Ventricular, 166, 224, 226 Ventricular fibrillation, 224, 226 Venules, 172, 226 Verapamil, 49, 134, 227 Vertebrae, 197, 220, 227 Vestibule, 177, 196, 217, 227 Veterinary Medicine, 70, 97, 112, 145, 227 Vibrio, 33, 176, 227 Vibrio cholerae, 33, 176, 227 Vinblastine, 73, 78, 81, 227 Vinca Alkaloids, 227 Vincristine, 93, 227 Vinorelbine, 17, 24, 93, 227 Vinyl Chloride, 127, 227 Viral, 6, 27, 163, 169, 190, 227 Virginiamycin, 21, 227 Virulence, 11, 13, 24, 79, 224, 227 Virus, 27, 34, 111, 129, 169, 190, 196, 205, 210, 215, 217, 227
Virus Diseases, 169, 227 Viscosity, 105, 163, 216, 227 Vitro, 8, 11, 12, 15, 17, 20, 33, 34, 36, 37, 38, 39, 40, 51, 52, 58, 70, 71, 72, 73, 77, 97, 112, 184, 190, 195, 210, 216, 223, 227 Vivo, 13, 15, 16, 34, 73, 227 Voriconazole, 60, 227 W Watchful waiting, 61, 227 White blood cell, 168, 198, 199, 200, 202, 204, 227 Whooping Cough, 209, 228 Windpipe, 223, 228 Wound Healing, 203, 228 Wound Infection, 126, 228 X X-ray, 30, 100, 110, 188, 203, 205, 228 Y Yeasts, 189, 209, 228 Z Zinc Acetate, 73, 228 Zygote, 179, 228 Zymogen, 176, 228
Index 243
244
Erythromycin