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

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

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Concerta: 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: 0-597-84382-1 1. Concerta-Popular works. I. Title.

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

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

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

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

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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CONCERTA ................................................................................................ 3 Overview........................................................................................................................................ 3 Federally Funded Research on Concerta ........................................................................................ 3 The National Library of Medicine: PubMed .................................................................................. 4 CHAPTER 2. NUTRITION AND CONCERTA ...................................................................................... 21 Overview...................................................................................................................................... 21 Finding Nutrition Studies on Concerta....................................................................................... 21 Federal Resources on Nutrition ................................................................................................... 25 Additional Web Resources ........................................................................................................... 26 CHAPTER 3. ALTERNATIVE MEDICINE AND CONCERTA ................................................................ 27 Overview...................................................................................................................................... 27 National Center for Complementary and Alternative Medicine.................................................. 27 Additional Web Resources ........................................................................................................... 27 General References ....................................................................................................................... 28 CHAPTER 4. DISSERTATIONS ON CONCERTA .................................................................................. 29 Overview...................................................................................................................................... 29 Dissertations on Concerta............................................................................................................ 29 Keeping Current .......................................................................................................................... 31 CHAPTER 5. CLINICAL TRIALS AND CONCERTA ............................................................................ 33 Overview...................................................................................................................................... 33 Recent Trials on Concerta............................................................................................................ 33 Keeping Current on Clinical Trials ............................................................................................. 36 CHAPTER 6. PATENTS ON CONCERTA ............................................................................................ 39 Overview...................................................................................................................................... 39 Patents on Concerta ..................................................................................................................... 39 Patent Applications on Concerta ................................................................................................. 48 Keeping Current .......................................................................................................................... 53 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 57 Overview...................................................................................................................................... 57 NIH Guidelines............................................................................................................................ 57 NIH Databases............................................................................................................................. 59 Other Commercial Databases....................................................................................................... 61 APPENDIX B. PATIENT RESOURCES ................................................................................................. 63 Overview...................................................................................................................................... 63 Patient Guideline Sources............................................................................................................ 63 Finding Associations.................................................................................................................... 65 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 67 Overview...................................................................................................................................... 67 Preparation................................................................................................................................... 67 Finding a Local Medical Library.................................................................................................. 67 Medical Libraries in the U.S. and Canada ................................................................................... 67 ONLINE GLOSSARIES.................................................................................................................. 73 Online Dictionary Directories ..................................................................................................... 73 CONCERTA DICTIONARY .......................................................................................................... 75 INDEX .............................................................................................................................................. 101

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

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

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

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

Project Title: TREATMENT OF ADHD IN PEDIATRIC PATIENTS WITH EPILEPSY Principal Investigator & Institution: Gonzalez-Heydrich, Joseph M.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Epilepsy is highly prevalent and associated with increased risk for psychiatric disorders. Patients with chronic recurrent seizures are

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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excluded from most pharmacological trials establishing standard treatments in pediatric psychiatry. Finding safe and effective treatments for psychiatric disorders in pediatric patients with epilepsy is of pressing public health importance. The purpose of this Mentored Patient-Oriented Research Development Award (K23) is for the candidate to become an independent clinical researcher in the psychopharmacologic treatment of psychiatric disorders in children and adolescents facing epilepsy. The proposal focuses on patients with comorbid ADHD and epilepsy. The project will be conducted at Children's Hospital Boston (CHB), which serves a large population of patients with epilepsy. Joseph Biederman, MD, with expertise in clinical trials in pediatric psychopharmacology will serve as the primary mentor. William R. Beardslee, MD, Chairman of Psychiatry at CHB will serve as the sponsor. Blaise Bourgeois, MD, Chairman of the Division of Epilepsy and Clinical Neurophysiology at CHB is the principal epilepsy consultant. Research plan: The aims are: 1) To perform a randomized placcbo controlled crossover trial of extended release methylphenidate (Concerta) in pediatric patients with comorbid ADHD and epilepsy; 2) To establish methods of assuring the safety of children with epilepsy in psychopharmacological clinical trials. Career development plan: The training will emphasize skills necessary for conducting randomized controlled clinical trials in youth with epilepsy comorbid with psychiatric disorders and to explore the neurobiological mechanisms underlying their increased risk for psychopathology. Didactic work in intervention research design, statistics, developmental psychopathology, and assessment methodologies for psychopathology and treatment response will complement supervision by the program consultants. The long-term goals of the candidate are to develop and evaluate treatments for children with comorbid psychiatric disorders and epilepsy as well as to investigate neurobiological correlates of the risk and response to treatment of these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.3 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Concerta, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Concerta” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Concerta (hyperlinks lead to article summaries):

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

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A dose-response study of OROS methylphenidate in children with attentiondeficit/hyperactivity disorder. Author(s): Stein MA, Sarampote CS, Waldman ID, Robb AS, Conlon C, Pearl PL, Black DO, Seymour KE, Newcorn JH. Source: Pediatrics. 2003 November; 112(5): E404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14595084&dopt=Abstract

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A positron emission tomography study of methylphenidate in adults with ADHD: alterations in resting blood flow and predicting treatment response. Author(s): Schweitzer JB, Lee DO, Hanford RB, Tagamets MA, Hoffman JM, Grafton ST, Kilts CD. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 May; 28(5): 967-73. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700698&dopt=Abstract

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A randomized, double-blind, crossover study of methylphenidate and lithium in adults with attention-deficit/hyperactivity disorder: preliminary findings. Author(s): Dorrego MF, Canevaro L, Kuzis G, Sabe L, Starkstein SE. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Summer; 14(3): 289-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154153&dopt=Abstract

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A slow start to the new millennium. Zyvox, Concerta and Mifeprex headline the year. Author(s): Cornell S. Source: Adv Nurse Pract. 2000 December; 8(12): 62-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397912&dopt=Abstract

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ADHD treatment with once-daily OROS methylphenidate: interim 12-month results from a long-term open-label study. Author(s): Wilens T, Pelham W, Stein M, Conners CK, Abikoff H, Atkins M, August G, Greenhill L, McBurnett K, Palumbo D, Swanson J, Wolraich M. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 April; 42(4): 424-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649629&dopt=Abstract

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An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Author(s): Tenenbaum S, Paull JC, Sparrow EP, Dodd DK, Green L. Source: J Atten Disord. 2002 September; 6(2): 49-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142861&dopt=Abstract

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Association of the 480 bp DAT1 allele with methylphenidate response in a sample of Irish children with ADHD. Author(s): Kirley A, Lowe N, Hawi Z, Mullins C, Daly G, Waldman I, McCarron M, O'Donnell D, Fitzgerald M, Gill M. Source: American Journal of Medical Genetics. 2003 August 15; 121B(1): 50-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898575&dopt=Abstract

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Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. Author(s): Kratochvil CJ, Heiligenstein JH, Dittmann R, Spencer TJ, Biederman J, Wernicke J, Newcorn JH, Casat C, Milton D, Michelson D. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 July; 41(7): 776-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108801&dopt=Abstract

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Attempted abuse of concerta. Author(s): Ciccone PE. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 July; 41(7): 756. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108796&dopt=Abstract

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Attention deficit/hyperactivity disorder and methylphenidate. A review of height/weight, cardiovascular, and somatic complaint side effects. Author(s): Rapport MD, Moffitt C. Source: Clinical Psychology Review. 2002 November; 22(8): 1107-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436807&dopt=Abstract

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Bupropion-methylphenidate combination and grand mal seizures. Author(s): Ickowicz A. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 October; 47(8): 790-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420664&dopt=Abstract

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Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Author(s): Volkow ND, Wang GJ, Fowler JS, Molina PE, Logan J, Gatley SJ, Gifford A, Ding YS, Wong C, Pappas NR, Zhu W, Swanson JM. Source: Psychopharmacology. 2003 March; 166(3): 264-70. Epub 2003 February 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589522&dopt=Abstract

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Combined treatment with methylphenidate and citalopram for accelerated response in the elderly: an open trial. Author(s): Lavretsky H, Kim MD, Kumar A, Reynolds CF 3rd. Source: The Journal of Clinical Psychiatry. 2003 December; 64(12): 1410-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14728100&dopt=Abstract

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Comments on effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR food evaluation study. Author(s): Gonzalez MA, Polli JE, Morgan JA. Source: Current Medical Research and Opinion. 2002; 18(7): Vii-X. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487510&dopt=Abstract

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Comparative efficacy of Adderall and methylphenidate in attentiondeficit/hyperactivity disorder: a meta-analysis. Author(s): Faraone SV, Biederman J, Roe C. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 468-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352269&dopt=Abstract

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Comparative efficacy of two once daily methylphenidate formulations (Ritalin LA and Concerta) and placebo in children with attention deficit hyperactivity disorder across the school day. Author(s): Lopez F, Silva R, Pestreich L, Muniz R. Source: Paediatric Drugs. 2003; 5(8): 545-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895137&dopt=Abstract

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Comparing the abuse potential of methylphenidate versus other stimulants: a review of available evidence and relevance to the ADHD patient. Author(s): Kollins SH. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 11: 14-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529325&dopt=Abstract

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Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users. Author(s): Heil SH, Holmes HW, Bickel WK, Higgins ST, Badger GJ, Laws HF, Faries DE. Source: Drug and Alcohol Dependence. 2002 July 1; 67(2): 149-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095664&dopt=Abstract

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Daily methylphenidate use slows the growth of children: a community based study. Author(s): Lisska MC, Rivkees SA. Source: J Pediatr Endocrinol Metab. 2003 June; 16(5): 711-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880120&dopt=Abstract

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Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies. Author(s): Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, Lindemulder E, Wigal S. Source: Archives of General Psychiatry. 2003 February; 60(2): 204-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578439&dopt=Abstract

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Dexmethylphenidate. Author(s): Keating GM, Figgitt DP. Source: Drugs. 2002; 62(13): 1899-904; Discussion 1905-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215063&dopt=Abstract

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Does increasing methylphenidate dose aid symptom control in ADHD? Author(s): Ibay AD, Bascelli LM, Graves RS, Hill J. Source: The Journal of Family Practice. 2003 May; 52(5): 400, 403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737774&dopt=Abstract

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Dopamine transporter gene and response to methylphenidate in attentiondeficit/hyperactivity disorder. Author(s): Roman T, Szobot C, Martins S, Biederman J, Rohde LA, Hutz MH. Source: Pharmacogenetics. 2002 August; 12(6): 497-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172219&dopt=Abstract

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Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: a pilot study. Author(s): Rohde LA, Roman T, Szobot C, Cunha RD, Hutz MH, Biederman J. Source: Synapse (New York, N.Y.). 2003 May; 48(2): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619042&dopt=Abstract

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Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Author(s): Schubiner H, Saules KK, Arfken CL, Johanson CE, Schuster CR, Lockhart N, Edwards A, Donlin J, Pihlgren E. Source: Experimental and Clinical Psychopharmacology. 2002 August; 10(3): 286-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233989&dopt=Abstract

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EEG differences between good and poor responders to methylphenidate in boys with the inattentive type of attention-deficit/hyperactivity disorder. Author(s): Clarke AR, Barry RJ, McCarthy R, Selikowitz M, Croft RJ. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 August; 113(8): 1191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139997&dopt=Abstract

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Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study. Author(s): Auiler JF, Liu K, Lynch JM, Gelotte CK. Source: Current Medical Research and Opinion. 2002; 18(5): 311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240794&dopt=Abstract

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Effects of methylphenidate discontinuation on cerebral blood flow in prepubescent boys with attention deficit hyperactivity disorder. Author(s): Langleben DD, Acton PD, Austin G, Elman I, Krikorian G, Monterosso JR, Portnoy O, Ridlehuber HW, Strauss HW. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 December; 43(12): 1624-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468511&dopt=Abstract

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Effects of methylphenidate on functional magnetic resonance relaxometry of the cerebellar vermis in boys with ADHD. Author(s): Anderson CM, Polcari A, Lowen SB, Renshaw PF, Teicher MH. Source: The American Journal of Psychiatry. 2002 August; 159(8): 1322-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153824&dopt=Abstract

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Effects of methylphenidate on heart rate and blood pressure among inpatients with acquired brain injury. Author(s): Burke DT, Glenn MB, Vesali F, Schneider JC, Burke J, Ahangar B, Goldstein R. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 July; 82(7): 493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819535&dopt=Abstract

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Effects of methylphenidate on the inhibitory postsynaptic potential in rat locus coeruleus neurons. Author(s): Kuwahata T, Ishimatsu M, Kidani Y, Akasu T. Source: Kurume Med J. 2002; 49(4): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652969&dopt=Abstract

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Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder. Author(s): Overtoom CC, Verbaten MN, Kemner C, Kenemans JL, van Engeland H, Buitelaar JK, van der Molen MW, van der Gugten J, Westenberg H, Maes RA, Koelega HS. Source: Behavioural Brain Research. 2003 October 17; 145(1-2): 7-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529800&dopt=Abstract

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Efficacy of a new pattern of delivery of methylphenidate for the treatment of ADHD: effects on activity level in the classroom and on the playground. Author(s): Swanson JM, Gupta S, Williams L, Agler D, Lerner M, Wigal S. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 November; 41(11): 1306-14. Erratum In: J Am Acad Child Adolesc Psychiatry. 2003 February; 42(2): 260. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410072&dopt=Abstract

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Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study. Author(s): Faraone SV, Short EJ, Biederman J, Findling RL, Roe C, Manos MJ. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2002 June; 5(2): 121-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135536&dopt=Abstract

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Efficacy of methylphenidate in patients with cerebral palsy and attention-deficit hyperactivity disorder (ADHD). Author(s): Gross-Tsur V, Shalev RS, Badihi N, Manor O. Source: Journal of Child Neurology. 2002 December; 17(12): 863-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593456&dopt=Abstract

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Electrophysiological investigation of the effectiveness of methylphenidate in children with and without ADHD. Author(s): Seifert J, Scheuerpflug P, Zillessen KE, Fallgatter A, Warnke A. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 July; 110(7): 821-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811642&dopt=Abstract

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Elevated striatal dopamine transporter in a drug naive patient with Tourette syndrome and attention deficit/ hyperactivity disorder: positive effect of methylphenidate. Author(s): Krause KH, Dresel S, Krause J, Kung HF, Tatsch K, Lochmuller H. Source: Journal of Neurology. 2002 August; 249(8): 1116-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420715&dopt=Abstract

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Extended-release methylphenidate (Ritalin LA). Author(s): Lyseng-Williamson KA, Keating GM. Source: Drugs. 2002; 62(15): 2251-9; Discussion 2260-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381228&dopt=Abstract

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Failed attempts at intranasal abuse of Concerta. Author(s): Jaffe SL. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 January; 41(1): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800205&dopt=Abstract

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Forty years of methylphenidate treatment in Attention-Deficit/ Hyperactivity Disorder. Author(s): Conners CK. Source: J Atten Disord. 2002; 6 Suppl 1: S17-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685516&dopt=Abstract

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Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder. Author(s): Greenhill L, Beyer DH, Finkleson J, Shaffer D, Biederman J, Conners CK, Gillberg C, Huss M, Jensen P, Kennedy JL, Klein R, Rapoport J, Sagvolden T, Spencer T, Swanson JM, Volkow N. Source: J Atten Disord. 2002; 6 Suppl 1: S89-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685523&dopt=Abstract

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High-dose methylphenidate treatment of attention deficit hyperactivity disorder in a preschooler. Author(s): Lipkin PH, Butz AM, Cozen MA. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Spring; 13(1): 103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804131&dopt=Abstract

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Illicit methylphenidate use in an undergraduate student sample: prevalence and risk factors. Author(s): Teter CJ, McCabe SE, Boyd CJ, Guthrie SK. Source: Pharmacotherapy. 2003 May; 23(5): 609-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741435&dopt=Abstract

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Inappropriate prescription of methylphenidate. Author(s): Cooper N. Source: N Z Med J. 2003 October 10; 116(1183): U636. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581947&dopt=Abstract

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Increased urine phenylethylamine after methylphenidate treatment in children with ADHD. Author(s): Kusaga A, Yamashita Y, Koeda T, Hiratani M, Kaneko M, Yamada S, Matsuishi T. Source: Annals of Neurology. 2002 September; 52(3): 372-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205654&dopt=Abstract

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Initiating treatment with modafinil for control of excessive daytime sleepiness in patients switching from methylphenidate: an open-label safety study assessing three strategies. Author(s): Thorpy MJ, Schwartz JR, Kovacevic-Ristanovic R, Hayduk R. Source: Psychopharmacology. 2003 June; 167(4): 380-5. Epub 2003 April 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709775&dopt=Abstract

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Interferon-induced fatigue in patients with melanoma: a pilot study of exercise and methylphenidate. Author(s): Schwartz AL, Thompson JA, Masood N. Source: Oncology Nursing Forum. 2002 August; 29(7): E85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183762&dopt=Abstract

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Isolated orofacial dyskinesia: a methylphenidate-induced movement disorder. Author(s): Senecky Y, Lobel D, Diamond GW, Weitz R, Inbar D. Source: Pediatric Neurology. 2002 September; 27(3): 224-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393134&dopt=Abstract

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Mechanism of action of methylphenidate: insights from PET imaging studies. Author(s): Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. Source: J Atten Disord. 2002; 6 Suppl 1: S31-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685517&dopt=Abstract

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Megadose intranasal methylphenidate (ritalin) abuse in adult attention deficit hyperactivity disorder. Author(s): Coetzee M, Kaminer Y, Morales A. Source: Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse. 2002 September; 23(3): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444349&dopt=Abstract

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Methylphenidate and intracortical excitability: opposite effects in healthy subjects and attention-deficit hyperactivity disorder. Author(s): Moll GH, Heinrich H, Rothenberger A. Source: Acta Psychiatrica Scandinavica. 2003 January; 107(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558545&dopt=Abstract

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Methylphenidate and substance abuse: a review of pharmacology, animal, and clinical studies. Author(s): Huss M, Lehmkuhl U. Source: J Atten Disord. 2002; 6 Suppl 1: S65-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685521&dopt=Abstract

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Methylphenidate and the cytochrome P450 system. Author(s): Baird R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 July; 48(6): 425-6; Author Reply 426. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894619&dopt=Abstract

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Methylphenidate as a possible cause of thrombocytopenia. Author(s): Kuperman AA, Yaniv I, Stahl B, Tamary H. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1146. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841835&dopt=Abstract

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Methylphenidate bioavailability from two extended-release formulations. Author(s): Gonzalez MA, Pentikis HS, Anderl N, Benedict MF, DeCory HH, Dirksen SJ, Hatch SJ. Source: Int J Clin Pharmacol Ther. 2002 April; 40(4): 175-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996212&dopt=Abstract

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Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD). Author(s): Vles JS, Feron FJ, Hendriksen JG, Jolles J, van Kroonenburgh MJ, Weber WE. Source: Neuropediatrics. 2003 April; 34(2): 77-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776228&dopt=Abstract

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Methylphenidate enhances both intracortical inhibition and facilitation in healthy adults. Author(s): Kirschner J, Moll GH, Fietzek UM, Heinrich H, Mall V, Berweck S, Heinen F, Rothenberger A. Source: Pharmacopsychiatry. 2003 March-April; 36(2): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734766&dopt=Abstract

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Methylphenidate facilitates and disinhibits the motor cortex in intact humans. Author(s): Ilic TV, Korchounov A, Ziemann U. Source: Neuroreport. 2003 April 15; 14(5): 773-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692481&dopt=Abstract

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Methylphenidate improves response inhibition in adults with attentiondeficit/hyperactivity disorder. Author(s): Aron AR, Dowson JH, Sahakian BJ, Robbins TW. Source: Biological Psychiatry. 2003 December 15; 54(12): 1465-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675812&dopt=Abstract

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Methylphenidate improves Stroop naming speed, but not response interference, in children with attention deficit hyperactivity disorder. Author(s): Bedard AC, Ickowicz A, Tannock R. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Winter; 12(4): 301-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625990&dopt=Abstract

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Methylphenidate in treatment of adults with Attention-Deficit/Hyperactivity Disorder. Author(s): Biederman J, Spencer T. Source: J Atten Disord. 2002; 6 Suppl 1: S101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685524&dopt=Abstract

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Methylphenidate produces a false-positive urine amphetamine screen. Author(s): Manzi S, Law T, Shannon MW. Source: Pediatric Emergency Care. 2002 October; 18(5): 401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395015&dopt=Abstract

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Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study. Author(s): Gothelf D, Gruber R, Presburger G, Dotan I, Brand-Gothelf A, Burg M, Inbar D, Steinberg T, Frisch A, Apter A, Weizman A. Source: The Journal of Clinical Psychiatry. 2003 October; 64(10): 1163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658963&dopt=Abstract

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Methylphenidate treatment in children with borderline IQ and mental retardation: analysis of three aggregated studies. Author(s): Aman MG, Buican B, Arnold LE. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Spring; 13(1): 29-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804124&dopt=Abstract

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Methylphenidate treats apathy in Parkinson's disease. Author(s): Chatterjee A, Fahn S. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Fall; 14(4): 461-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426416&dopt=Abstract

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Methylphenidate-evoked potentiation of extracellular dopamine in the brain of adolescents with premature birth: correlation with attentional deficit. Author(s): Rosa Neto P, Lou H, Cumming P, Pryds O, Gjedde A. Source: Annals of the New York Academy of Sciences. 2002 June; 965: 434-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105118&dopt=Abstract

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Methylphenidate-induced obsessive-compulsive symptoms in an elderly man. Author(s): Serby M. Source: Cns Spectr. 2003 August; 8(8): 612-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907924&dopt=Abstract

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Methylphenidate-induced plasticity: what should we be looking for? Author(s): Hyman SE. Source: Biological Psychiatry. 2003 December 15; 54(12): 1310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675793&dopt=Abstract

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Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing. Author(s): Rubia K, Noorloos J, Smith A, Gunning B, Sergeant J. Source: Journal of Abnormal Child Psychology. 2003 June; 31(3): 301-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774863&dopt=Abstract

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Neurofeedback treatment for attention-deficit/hyperactivity disorder in children: a comparison with methylphenidate. Author(s): Fuchs T, Birbaumer N, Lutzenberger W, Gruzelier JH, Kaiser J. Source: Applied Psychophysiology and Biofeedback. 2003 March; 28(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737092&dopt=Abstract

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Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Author(s): Pelham WE, Gnagy EM, Burrows-Maclean L, Williams A, Fabiano GA, Morrisey SM, Chronis AM, Forehand GL, Nguyen CA, Hoffman MT, Lock TM, Fielbelkorn K, Coles EK, Panahon CJ, Steiner RL, Meichenbaum DL, Onyango AN, Morse GD. Source: Pediatrics. 2001 June; 107(6): E105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389303&dopt=Abstract

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Oral methylphenidate-alcohol co-abuse. Author(s): Barrett SP, Pihl RO. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 633-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454570&dopt=Abstract

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Paediatric methylphenidate (Ritalin) restrictive conditions of prescription in France. Author(s): Frances C, Hoizey G, Millart H, Trenque T. Source: British Journal of Clinical Pharmacology. 2004 January; 57(1): 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14678352&dopt=Abstract

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Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report. Author(s): Bruera E, Driver L, Barnes EA, Willey J, Shen L, Palmer JL, Escalante C. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 December 1; 21(23): 4439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645434&dopt=Abstract

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Pediatric methylphenidate exposures: 7-year experience of poison centers in the United States. Author(s): Klein-Schwartz W. Source: Clinical Pediatrics. 2003 March; 42(2): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659390&dopt=Abstract

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Pharmacokinetics of methylphenidate after oral administration of two modifiedrelease formulations in healthy adults. Author(s): Markowitz JS, Straughn AB, Patrick KS, DeVane CL, Pestreich L, Lee J, Wang Y, Muniz R. Source: Clinical Pharmacokinetics. 2003; 42(4): 393-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648029&dopt=Abstract

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Poison centers' experience with methylphenidate abuse in pre-teens and adolescents. Author(s): Klein-Schwartz W, McGrath J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 March; 42(3): 288-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595781&dopt=Abstract

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Prevalence of and change in the prescription of methylphenidate in Israel over a 2year period. Author(s): Fogelman Y, Vinker S, Guy N, Kahan E. Source: Cns Drugs. 2003; 17(12): 915-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962530&dopt=Abstract

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Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Author(s): Wolraich ML, Greenhill LL, Pelham W, Swanson J, Wilens T, Palumbo D, Atkins M, McBurnett K, Bukstein O, August G. Source: Pediatrics. 2001 October; 108(4): 883-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11581440&dopt=Abstract

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Rate dependency revisited: understanding the effects of methylphenidate in children with attention deficit hyperactivity disorder. Author(s): Teicher MH, Polcari A, Anderson CM, Andersen SL, Lowen SB, Navalta CP. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Spring; 13(1): 41-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804125&dopt=Abstract

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Reinforcing, subject-rated, and physiological effects of intranasal methylphenidate in humans: a dose-response analysis. Author(s): Stoops WW, Glaser PE, Rush CR. Source: Drug and Alcohol Dependence. 2003 August 20; 71(2): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927656&dopt=Abstract

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Relative lack of cognitive effects of methylphenidate in elderly male volunteers. Author(s): Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ. Source: Psychopharmacology. 2003 August; 168(4): 455-64. Epub 2003 May 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734634&dopt=Abstract

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Reply to comments by Gonzalez et al. on the CONCERTA, Adderall XR Food Evaluation (CAFE) study. Author(s): Auiler JF, Lynch JM, Gelotte CK. Source: Current Medical Research and Opinion. 2003; 19(1): 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661783&dopt=Abstract

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Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial. Author(s): Galanter CA, Carlson GA, Jensen PS, Greenhill LL, Davies M, Li W, Chuang SZ, Elliott GR, Arnold LE, March JS, Hechtman L, Pelham WE, Swanson JM. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Summer; 13(2): 12336. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880507&dopt=Abstract

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Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002. Author(s): Rapoport JL, Inoff-Germain G. Source: J Atten Disord. 2002; 6 Suppl 1: S57-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685519&dopt=Abstract

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Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: results from imaging studies. Author(s): Volkow ND, Fowler JS, Wang GJ, Ding YS, Gatley SJ. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 December; 12(6): 557-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468018&dopt=Abstract

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Seizures associated with venlafaxine, methylphenidate, and zolpidem. Author(s): Tavakoli SA, Gleason OC. Source: Psychosomatics. 2003 May-June; 44(3): 262-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724513&dopt=Abstract

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Serum and brain concentrations of methylphenidate: implications for use and abuse. Author(s): Swanson JM, Volkow ND. Source: Neuroscience and Biobehavioral Reviews. 2003 November; 27(7): 615-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14624806&dopt=Abstract

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Successful treatment of intractable hiccup with methylphenidate in a lung cancer patient. Author(s): Marechal R, Berghmans T, Sculier P. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 February; 11(2): 126-8. Epub 2002 December 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560943&dopt=Abstract

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The acute effect of methylphenidate on cerebral blood flow in boys with attentiondeficit/hyperactivity disorder. Author(s): Szobot CM, Ketzer C, Cunha RD, Parente MA, Langleben DD, Acton PD, Kapczinski F, Rohde LA. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2003 March; 30(3): 423-6. Epub 2003 January 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634972&dopt=Abstract

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The effect of methylphenidate on three forms of response inhibition in boys with AD/HD. Author(s): Scheres A, Oosterlaan J, Swanson J, Morein-Zamir S, Meiran N, Schut H, Vlasveld L, Sergeant JA. Source: Journal of Abnormal Child Psychology. 2003 February; 31(1): 105-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597703&dopt=Abstract

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The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder. Author(s): Hawk LW Jr, Yartz AR, Pelham WE Jr, Lock TM. Source: Psychopharmacology. 2003 January; 165(2): 118-27. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417963&dopt=Abstract

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The efficacy of 2 different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder. Author(s): Bouffard R, Hechtman L, Minde K, Iaboni-Kassab F. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 September; 48(8): 546-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14574830&dopt=Abstract

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The functioning neuronal transporter for dopamine: kinetic mechanisms and effects of amphetamines, cocaine and methylphenidate. Author(s): Schenk JO. Source: Prog Drug Res. 2002; 59: 111-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458965&dopt=Abstract

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The hazards of legislative restraints on legislative decisions--the case of methylphenidate (ritalin) vs. paracetamol (acamol). Author(s): Apter A. Source: The Israel Journal of Psychiatry and Related Sciences. 2003; 40(3): 162-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14619674&dopt=Abstract

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Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in attention deficit hyperactivity disorder. Author(s): Maayan R, Yoran-Hegesh R, Strous R, Nechmad A, Averbuch E, Weizman A, Spivak B. Source: Neuropsychobiology. 2003; 48(3): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586159&dopt=Abstract

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Treatment effects of methylphenidate on behavioral adjustment in children with mental retardation and ADHD. Author(s): Pearson DA, Santos CW, Roache JD, Casat CD, Loveland KA, Lachar D, Lane DM, Faria LP, Cleveland LA. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 February; 42(2): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544181&dopt=Abstract

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Use of methylphenidate for attention-deficit hyperactivity disorder in patients with epilepsy or electroencephalographic abnormalities. Author(s): Gucuyener K, Erdemoglu AK, Senol S, Serdaroglu A, Soysal S, Kockar AI. Source: Journal of Child Neurology. 2003 February; 18(2): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693777&dopt=Abstract

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Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. Author(s): Volkow ND, Swanson JM. Source: The American Journal of Psychiatry. 2003 November; 160(11): 1909-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594733&dopt=Abstract

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What are the long-term effects of methylphenidate treatment? Author(s): Volkow ND, Insel TR. Source: Biological Psychiatry. 2003 December 15; 54(12): 1307-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675792&dopt=Abstract

21

CHAPTER 2. NUTRITION AND CONCERTA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Concerta.

Finding Nutrition Studies on Concerta 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.4 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 “Concerta” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

5-HT3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat. Author(s): Department of Mental Health and Alcohol Research, Drug Research Unit, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland. [email protected] Source: Kankaanpaa, Aino Meririnne, Esa Seppala, Timo Psychopharmacology-(Berl). 2002 February; 159(4): 341-50 0033-3158

•

A slow start to the new millennium. Zyvox, Concerta and Mifeprex headline the year. Source: Cornell, S Adv-Nurse-Pract. 2000 December; 8(12): 62-4 1096-6293

•

Adverse response to methylphenidate in combination with valproic acid. Author(s): Child Development Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. Source: Gara, L Roberts, W J-Child-Adolesc-Psychopharmacol. 2000 Spring; 10(1): 39-43 1044-5463

•

Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Author(s): Department of Psychiatry, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA. [email protected] Source: Andersen, Susan L Arvanitogiannis, Andreas Pliakas, Andrea M LeBlanc, Celeste Carlezon, William A Jr Nat-Neurosci. 2002 January; 5(1): 13-4 1097-6256

•

An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Author(s): The Attention Deficit Center in St. Louis 63141, MO. Source: Tenenbaum, S Paull, J C Sparrow, E P Dodd, D K Green, L J-Atten-Disord. 2002 September; 6(2): 49-60 1087-0547

•

Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications. Author(s): Department of Neurology, University School of Medicine, Turin, Italy. Source: Cantello, R Aguggia, M Gilli, M Delsedime, M Riccio, A Rainero, I Mutani, R Arch-Neurol. 1988 September; 45(9): 973-6 0003-9942

•

Behavioral pharmacological similarities between methylphenidate and cocaine in cocaine abusers. Author(s): Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, USA. [email protected] Source: Rush, C R Baker, R W Exp-Clin-Psychopharmacol. 2001 February; 9(1): 59-73 1064-1297

•

Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of “high”. Author(s): Brookhaven National Laboratory, Upton, New York, USA. Source: Volkow, N D Wang, G J Fowler, J S Gatley, S J Logan, J Ding, Y S Dewey, S L Hitzemann, R Gifford, A N Pappas, N R J-Pharmacol-Exp-Ther. 1999 January; 288(1): 1420 0022-3565

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Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Author(s): Psychobiology Section, National Institute on Drug Abuse, Division of Intramural Research, Baltimore, MD 21224, USA. [email protected]

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Source: Izenwasser, S Coy, A E Ladenheim, B Loeloff, R J Cadet, J L French, D Eur-JPharmacol. 1999 June 4; 373(2-3): 187-93 0014-2999 •

Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain. Author(s): Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. [email protected] Source: Volkow, N D Fowler, J S Gatley, S J Dewey, S L Wang, G J Logan, J Ding, Y S Franceschi, D Gifford, A Morgan, A Pappas, N King, P Synapse. 1999 January; 31(1): 5966 0887-4476

•

Depletion of catecholamines in the brain of rats differentially affects stimulation of locomotor activity by caffeine, D-amphetamine, and methylphenidate. Author(s): Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322. Source: Finn, I B Iuvone, P M Holtzman, S G Neuropharmacology. 1990 July; 29(7): 62531 0028-3908

•

Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. Author(s): Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. [email protected] Source: Gatley, S J Volkow, N D Gifford, A N Fowler, J S Dewey, S L Ding, Y S Logan, J Psychopharmacology-(Berl). 1999 September 1; 146(1): 93-100 0033-3158

•

Dynamic changes in sensitivity occur during the acute response to cocaine and methylphenidate. Author(s): Psychiatry Department (0603), UCSD School of Medicine, La Jolla 92093, USA. [email protected] Source: Kuczenski, R Segal, D S Psychopharmacology-(Berl). 1999 November; 147(1): 96103 0033-3158

•

Effect of food on the pharmacokinetics of osmotic controlled-release methylphenidate HCl in healthy subjects. Author(s): Department of Clinical Pharmacology, ALZA Corp, 1900 Charleston Road, Mountain View, CA 94039, USA. [email protected] Source: Modi, N B Wang, B Hu, W T Gupta, S K Biopharm-Drug-Dispos. 2000 January; 21(1): 23-31 0142-2782

•

Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Author(s): Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA. [email protected] Source: Levin, E D Conners, C K Silva, D Canu, W March, J Exp-Clin-Psychopharmacol. 2001 February; 9(1): 83-90 1064-1297

•

Effects of food on the pharmacokinetics of methylphenidate. Author(s): PharmaLytics Inc, Saskatoon, SK, Canada. Source: Midha, K K McKay, G Rawson, M J Korchinski, E D Hubbard, J W Pharm-Res. 2001 August; 18(8): 1185-9 0724-8741

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Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? Author(s): Department of Chemistry, Washington State University, Pullman, USA. Source: Wayment, H K Deutsch, H Schweri, M M Schenk, J O J-Neurochem. 1999 March; 72(3): 1266-74 0022-3042

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Effects of repeated methylphenidate treatment in the young rat: sensitization of both locomotor activity and stereotyped sniffing. Author(s): Department of Psychology, California State University, San Bernardino 92407-2397, USA. [email protected] Source: McDougall, S A Collins, R L Karper, P E Watson, J B Crawford, C A Exp-ClinPsychopharmacol. 1999 August; 7(3): 208-18 1064-1297

•

Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Author(s): Departments of Cell Biology and Anatomy, Finch University of Health Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA. Source: Brandon, C L Marinelli, M Baker, L K White, F J Neuropsychopharmacology. 2001 November; 25(5): 651-61 0893-133X

•

Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder. Author(s): Yale University, School of Nursing, New Haven, Connecticut 06510, USA. Source: Hamrin, V Bailey, K J-Child-Adolesc-Psychopharmacol. 2001 Fall; 11(3): 301-9 1044-5463

•

Inhibition of methylphenidate-induced behaviors in rats: differences among neuroleptics. Author(s): Neurobiology Division, Fondax, Puteaux, France. Source: Koek, W Colpaert, F C J-Pharmacol-Exp-Ther. 1993 October; 267(1): 181-91 00223565

•

Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Author(s): Brookhaven National Laboratory, Upton, New York 11973, USA. [email protected] Source: Volkow, N D Wang, G J Fowler, J S Fischman, M Foltin, R Abumrad, N N Gatley, S J Logan, J Wong, C Gifford, A Ding, Y S Hitzemann, R Pappas, N Life-Sci. 1999; 65(1): PL7-12 0024-3205

•

Naloxone augments the hypothalamic-pituitary-adrenal axis response to methylphenidate in normal subjects. Author(s): Affective Disorders Unit, Sunnyside Hospital, Christchurch, New Zealand. Source: Joyce, P R Donald, R A J-Psychiatr-Res. 1987; 21(3): 297-300 0022-3956

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Neuropharmacologic treatment of hemineglect: a case report comparing bromocriptine and methylphenidate. Author(s): Department of Rehabilitation Medicine, Emory University, Atlanta, GA 30322, USA. Source: Hurford, P Stringer, A Y Jann, B Arch-Phys-Med-Rehabil. 1998 March; 79(3): 346-9 0003-9993

•

Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy. Author(s): Department of Pediatrics, Louisiana State University School of Medicine, New Orleans, Louisiana 70112, USA. Source: Rao, J K Julius, J R Breen, T J Blethen, S L Pediatrics. 1998 August; 102(2 Pt 3): 497-500 0031-4005

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•

Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning. Author(s): Department of Psychiatry & Neuroscience Program, Harvard Medical School and Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA. Source: Davids, Eugen Zhang, Kehong Tarazi, Frank I Baldessarini, Ross J Psychopharmacology-(Berl). 2002 February; 160(1): 92-8 0033-3158

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The concurrent use of lithium and methylphenidate in a child. Source: Licamele, W L Goldberg, R L J-Am-Acad-Child-Adolesc-Psychiatry. 1989 September; 28(5): 785-7 0890-8567

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The use of methylphenidate in the treatment of refractory neurocardiogenic syncope. Author(s): Department of Medicine, Medical College of Ohio, Toledo 43699, USA. Source: Grubb, B P Kosinski, D Mouhaffel, A Pothoulakis, A Pacing-Clin-Electrophysiol. 1996 May; 19(5): 836-40 0147-8389

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Treatment for hyperactive children: homeopathy and methylphenidate compared in a family setting. Author(s): Spezialarzt FMH fur Kinder und Jugendliche, FA Homoopathie SVHA, Laupen, Switzerland. [email protected] Source: Frei, H Thurneysen, A Br-Homeopath-J. 2001 October; 90(4): 183-8 0007-0785

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Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer. Source: Bruera, E Brenneis, C Paterson, A H MacDonald, R N J-Pain-Symptom-Manage. 1989 March; 4(1): 3-6 0885-3924

•

Visual event related potentials after methylphenidate and sodium valproate in children with attention deficit hyperactivity disorder. Author(s): Department of Neurology, North Shore University Hospital, Cornell University Medical College, Manhasset, New York 11030. Source: Frank, Y Clin-Electroencephalogr. 1993 January; 24(1): 19-24 0009-9155

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

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

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

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

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A slow start to the new millennium. Zyvox, Concerta and Mifeprex headline the year. Author(s): Cornell S. Source: Adv Nurse Pract. 2000 December; 8(12): 62-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397912&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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to Concerta; 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 Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Attention Deficit-Hyperactivity Disorder Source: Healthnotes, Inc.; www.healthnotes.com

•

Herbs and Supplements Ginseng (Panax) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10029,00.html Methylphenidate Source: Healthnotes, Inc.; www.healthnotes.com Mixed Amphetamines Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. DISSERTATIONS ON CONCERTA Overview In this chapter, we will give you a bibliography on recent dissertations relating to Concerta. 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 “Concerta” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Concerta, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Concerta 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 Concerta. 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: •

Analysis and Pharmacokinetics of Methylphenidate (Ritalin) Studies in Hyperactive Children by Chan, Ying-Pui Mick; PhD from University of Toronto (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK47027

•

Causal Attributions Made by Parents of Children Taking Methylphenidate for Attention-Deficit Hyperactivity Disorder by Jenson, Cary, PhD from Virginia Commonwealth University, 1996, 110 pages http://wwwlib.umi.com/dissertations/fullcit/9627437

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Cognitive and Behavioral Effects of Methylphenidate on Conduct Disordered Boys by Bawden, Harry N; PhD from Carleton University (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29871

•

Dosage Effects of Methylphenidate on the Activity Level of Hyperactive Children by Witt, Peter Arthur, PhD from University of Illinois at Urbana-Champaign, 1971, 111 pages http://wwwlib.umi.com/dissertations/fullcit/7212442

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Effect of Two Levels of Methylphenidate Hydrochloride for Hyperkinetic Children on Measures of Attention and Mother-child Interaction by Bambrick, James R; PhD from University of Windsor (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK41929

•

Effects of Methylphenidate on Information Processing and Reading in a Group of Hyperactive Children by Ballinger, Carolyn Lois Tucker, PhD from University of Washington, 1982, 93 pages http://wwwlib.umi.com/dissertations/fullcit/8218198

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Effects of Methylphenidate on Right Hemisphere Functioning in ADHD by Campbell-Cholvat, Lorraine, PhD from University of Toronto (Canada), 1993, 139 pages http://wwwlib.umi.com/dissertations/fullcit/NN86280

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Methylphenidate Protocol for Use in Broad Practice by Wojtowicz, Alexandra, PhD from Temple University, 1995, 146 pages http://wwwlib.umi.com/dissertations/fullcit/9527547

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Parents' Decision-Making Process in Methylphenidate Administration: Educational Policy Considerations by Slimmer, Lynda Walton, PhD from University of Illinois at Chicago, 1984, 127 pages http://wwwlib.umi.com/dissertations/fullcit/8411339

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The Differential Dose Effects of Methylphenidate on Hyperactive Children and Their Mothers by Lipton, Meryl Esta, PhD from University of Minnesota, 1980, 240 pages http://wwwlib.umi.com/dissertations/fullcit/8025476

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The Effect of Methylphenidate and Amygdalectomy on Active Avoidance Performance in the Rat by Yeudall, Lorne T; AdvDeg from University of Alberta (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06771

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The Effect of Methylphenidate on Self-Concept and Locus of Control of Hyperactive Children by Thompson, Lynda M; PhD from University of Toronto (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK40969

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The Effects of Methylphenidate and Thioridazine upon Attention, Arousal and Activity in Mentally Retarded Youngsters by Tate, Douglas Lloyd; PhD from Carleton University (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK24232

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The Effects of Methylphenidate Dose on Attention and Nonverbal Learning in Children with Attention-Deficit Hyperactivity Disorder (Attention Deficit Hyperactivity Disorder) by O'Toole, Kathleen Mary, PhD from Georgia State University, 1994, 98 pages http://wwwlib.umi.com/dissertations/fullcit/9507429

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The Effects of Methylphenidate during Rest, Exercise, and Recovery upon the Circulorespiratory Responses of Hyperactive Children. by Ballard, Joyce Elaine, PhD from University of Illinois at Urbana-Champaign, 1975, 240 pages http://wwwlib.umi.com/dissertations/fullcit/7514079

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The Effects of Methylphenidate on Avoidance Learning and Risk-taking by Hyperkinetic Children by Freeman, Richard J; PhD from University of Waterloo (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK37852

Dissertations 31

•

The Effects of Methylphenidate on Learning in Hyperactive Children: the Stimulus Equivalence Paradigm by Vyse, Stuart Arthur, PhD from University of Rhode Island, 1987, 130 pages http://wwwlib.umi.com/dissertations/fullcit/8800163

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The Effects of Methylphenidate on Self-regulatory Speech of Children with Attention Deficit Hyperactivity Disorder (Hyperactivity) by Coffey, Laura Denton, PhD from Indiana State University, 1993, 155 pages http://wwwlib.umi.com/dissertations/fullcit/9322597

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The Effects of Methylphenidate on the Attention Span and Learning Performance of Hyperactive Children. by Kozuch, Donna Parko, PhD from The American University, 1977, 85 pages http://wwwlib.umi.com/dissertations/fullcit/7804614

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The Effects of Methylphenidate on the Reading Behaviors of Elementary School Children Diagnosed As Hyperactive by Hynd, Cynthia R., EDD from University of Georgia, 1984, 376 pages http://wwwlib.umi.com/dissertations/fullcit/8421123

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The Effects of Methylphenidate on the Repeated Acquisition Performance of Children with Attention Deficit Disorder by Giuliano, Christopher Paul, PhD from Western Michigan University, 1991, 65 pages http://wwwlib.umi.com/dissertations/fullcit/9201559

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The Utility of Reading to Read with Boys with ADHD during Optimal Versus Nonoptimal Methylphenidate Effect Windows by Kastner, Joseph William, PhD from The University of Southern Mississippi, 1997, 100 pages http://wwwlib.umi.com/dissertations/fullcit/9809151

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Verbal and Porteus Maze Performance of Learning Disabled Children: Effects of Methylphenidate and Input Organization by Freston, Cyrus Wheelock, II, PhD from The University of Texas at Austin, 1971, 133 pages http://wwwlib.umi.com/dissertations/fullcit/7215757

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

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

Recent Trials on Concerta The following is a list of recent trials dedicated to Concerta.5 Further information on a trial is available at the Web site indicated. •

Dextroamphetamine-Amphetamine Compared With Methylphenidate in Treating Children With Depression and Problems With Memory, Attention, and Thinking Caused By Cancer Treatment Condition(s): unspecified childhood solid tumor, protocol specific; Depression; neurotoxicity Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Stimulant drugs such as dextroamphetamineamphetamine and methylphenidate may decrease depression and may help improve memory, attention, and thinking problems caused by central nervous system (CNS) treatment for cancer. PURPOSE: Randomizedphase II trial to compare the effectiveness of dextroamphetamine-amphetamine with that of methylphenidate in treating depression and problems with memory, attention, and thinking in children who have undergone CNS treatment for cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069927

5

These are listed at www.ClinicalTrials.gov.

34

•

Concerta

Methylphenidate to Improve Quality of Life in Patients Undergoing Radiation Therapy for Brain Tumors Condition(s): adult brain tumor; brain metastases; cognitive and functional effects; Depression; Fatigue; Quality of Life Study Status: This study is currently recruiting patients. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Methylphenidate may decrease side effects of radiation therapy. It is not yet known if methylphenidate is effective in improving quality of life in patients with primary or metastatic brain tumors. PURPOSE: Randomizedphase III trial to determine the effectiveness of methylphenidate in improving quality of life in patients who have brain tumors and are undergoing radiation therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031798

•

Methylphenidate in Children and Adolescents with Pervasive Developmental Disorders Condition(s): Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Pervasive Development Disorders Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will evaluate the efficacy and safety of methylphenidate for treating hyperactivity, impulsiveness, and distractibility in 60 children and adolescents with Pervasive Developmental Disorders (PDD). Methylphenidate (Ritalin)is approved by the Food and Drug Administration for the treatment of children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Data supporting its safety and effectiveness in treating ADHD symptoms in PDD are limited. Children and adolescents who do not show a positive response to methylphenidate will be invited to participate in a pilot study of the non-stimulant medication guanfacine (Tenex). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025779

•

Methylphenidate in Treating Patients With Melanoma Condition(s): unspecified adult solid tumor, protocol specific; Fatigue; Quality of Life Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: Methylphenidate may relieve some of the side effects of chemotherapy in patients with melanoma. It is not known whether receiving methylphenidate is more effective than receiving no further therapy in treating patients

Clinical Trials 35

with melanoma. PURPOSE: Randomized phase III trial to determine if methylphenidate is more effective than no further therapy for the relief of fatigue and drowsiness in treating patients with melanoma who have received high-dose interferon alfa for 8-24 weeks. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003266 •

Methylphenidate Raclopride PET test - 11 Condition(s): Cocaine-Related Disorders; Substance-Related Disorders Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); New York MDRU Purpose - Excerpt: PET test-retest Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015301

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Pediatric Traumatic Brain Injury: Methylphenidate Effects on Early Recovery Condition(s): Brain Injuries Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Murray Fellowship Purpose - Excerpt: Traumatic Brain Injury (TBI) is the leading cause of acquired long term disability among children and young adults. Deficits in attention and memory are common and persist for years after moderate or severe TBI. The similarity between these symptoms and those of children with AD/HD, the efficacy of methylphenidate in the treatment of AD/HD, and the efficacy of methylphenidate in improving recovery of animals with brain injuries, support the need to study methylphenidate effects in children with TBI. This investigation of methylphenidate in children with moderate to severe TBI aims to: (1) Assess the acute effects of 2 different dosages of methylphenidate on attention and reaction time when the medication is administered to children early in recovery; (2) Assess the ability of 8 weeks of methylphenidate to improve the rate of recovery of cognitive, memory, and attentional skills in children with TBI; (3) Identify the frequency of common methylphenidate side effects in children with TBI. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035139

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Patents on Concerta By performing a patent search focusing on Concerta, 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

6Adapted

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

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on Concerta: •

7-amino-2-heptenoates and their use in the preparation of methylphenidate Inventor(s): Fox; Martin Edward (Cambridge, GB), Paul; Jane Marie (Cambridge, GB) Assignee(s): Medeva Europe Limited (gb) Patent Number: 6,031,124 Date filed: September 25, 1998 Abstract: The subject invention pertains to compounds of the formula Y.sup.1 Y.sup.2 N--(CH.sub.2).sub.4 --CH.dbd.C(Ph)--X wherein Y.sup.1 and Y.sup.2 are independently H or a removable blocking group, or Y.sup.1 and Y.sup.2 together are a removable divalent blocking group; and X is COOCH.sub.3 or a group convertible thereto. Such a compound may be cyclised, by Michael addition, to give methylphenidate, if necessary after removing blocking group(s) and converting X to COOCH.sub.3. The subject invention also pertains to methods for preparing compounds of the invention. Excerpt(s): This invention relates to the synthesis of methylphenidate by cyclisation of new 7-amino-2-heptenoates. Methylphenidate has utility as a therapeutic agent, e.g. in the treatment of attention-deficient hyperactivity disorder. It was first prepared as a mixture of the erythro and threo racemates. U.S. Pat. No. 2,957,880 discloses its synthesis and also studies upon the two racemic mixtures, which revealed that the therapeutic activity resides in the threo diastereomer. wherein R* is the chiral auxiliary.alpha.methylbenzylamine and R is lower alkyl. This structure is indicated as suitable for cyclisation to 1-(1-phenylethyl)-2-hydroxy-5-piperidinone, en route to antihistaminic agents. Web site: http://www.delphion.com/details?pn=US06031124__

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Chronic, bolus administration of D-threo methylphenidate Inventor(s): Dariani; Maghsoud M. (Fanwood, NJ), Zeitlin; Andrew L. (Millington, NJ), Zeldis; Jerome B. (Princeton, NJ) Assignee(s): Celegene Corporation (warren, Nj) Patent Number: 5,922,736 Date filed: September 29, 1997 Abstract: Chronic bolus administration of D-threo methylphenidate is provided. The administration of the D-threo isomer eliminates adverse side effects associated with the DL racemate, and provides improved effectiveness. The compositions and methods of the invention are useful in treating nervous system disorders including attention deficit disorder, attention deficit hyperactivity disorder, and cognitive decline associated with systemic diseases such as acquired immunodeficiency syndrome. Excerpt(s): The present invention is directed to methods and compositions for treating nervous system disorders such as attention deficit disorder, attention deficit hyperactivity disorder, cognitive decline associated with acquired immunodeficiency syndrome, and similar conditions. The methods involve the administration of a single, bolus dose of a composition comprising D-threo methylphenidate. The compositions are substantially free of L-threo methylphenidate and of erythro forms of

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methylphenidate. Attention Deficit Disorder (ADD), a commonly diagnosed nervous system illness in children, is generally treated with methylphenidate hydrochloride (available commercially as, e.g., Ritalin.RTM.). Symptoms of ADD include distractibility and impulsivity. A related disorder, termed Attention Deficit Hyperactivity Disorder (ADHD), is further characterized by symptoms of hyperactivity, and is also treated with methylphenidate hydrochloride. Methylphenidate drugs have also been used to treat cognitive decline in patients with Acquired Immunodeficiency Syndrome (AIDS) or AIDS related conditions. See, e.g., Brown, G., Intl J. Psych. Med. 25(1): 21-37 (1995); Holmes et al., J. Clin. Psychiatry 50: 5-8 (1989). Clinically, the threo pair of enanitiomers of methylphenidate hydrochloride is generally administered for the treatment of ADD and ADHD. The hydrochloride salt is commonly referred to simply as "methylphenidate". Unless indicated otherwise, the term "methylphenidate" is used broadly herein to include methylphenidate and pharmaceutically acceptable salts thereof, including methylphenldate hydrochloride. Web site: http://www.delphion.com/details?pn=US05922736__ •

Compositions and methods for treatment of attention deficit disorder and attention deficit/hyperactivity disorder with methylphenidate Inventor(s): Dixon; Terese A. (Miami, FL), Mantelle; Juan (Miami, FL) Assignee(s): Noven Pharmaceuticals, Nc. (miami, Fl) Patent Number: 6,210,705 Date filed: September 30, 1998 Abstract: The invention relates to a method of treating Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) and compositions for topical application of methylphenidate comprising methylphenidate in a flexible, finite system wherein the methylphenidate is present in an amount sufficient to achieve substantially zero order kinetics for delivery to the skin or mucosa of a patient in need thereof over a period of time at least 10 hours. Excerpt(s): The present invention relates to compositions and methods of treatment of Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) by means of topical application of methylphenidate in a pharmaceutically acceptable adhesive carrier, in an amount sufficient to achieve substantially zero-order kinetics over a period of at least 10 hours. Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) (severally and collectively hereinafter referred to as "AD") are developmental disorders of self-control. They consist of problems with attention span, impulse control and activity level. These problems are reflected in impairment of a person's will or capacity to control his or her own behavior relative to the passage of time and to keep future goals and consequences in mind. Traditionally, methylphenidate has been used as the drug of choice for the treatment of AD in both children and adults for several reasons. Methylphenidate, described in U.S. Pat. No. 2,957,880, is a central nervous system stimulant. Though not an amphetamine, methylphenidate functions in a similar way in the brain. The current commercially available dosage form (Ritalin.RTM. tablets) and available strengths of the tablets fall short of providing effective treatment for a significant portion of the patient's waking hours. Methylphenidate has a short duration of action of from about 2 to 4 hours. A controlled release tablet of methylphenidate is commercially available, but is available only in one strength. This product, which was designed to eliminate the need for multiple administration of a tablet during the school day for children and reduce dosing

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to either once or twice a day, falls short of providing effective treatment for a significant portion of the patient's waking hours. Web site: http://www.delphion.com/details?pn=US06210705__ •

Controlled/modified release oral methylphenidate formulations Inventor(s): Darke; Andrew (Ontario, CA), Goldenheim; Paul D. (Wilton, CT), Krishnamurthy; Thinnayam N. (Ontario, CA), Oshlack; Benjamin (New York, NY), Sackler; Richard S. (Greenwich, CT) Assignee(s): Euro-celtique, S.a. (luxembourg, Lu) Patent Number: 6,673,367 Date filed: December 16, 1999 Abstract: The invention is directed to oral modified/controlled release methylphenidate formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release methylphenidate formulations, and the duration of effect falls rapidly at the end of the dosing interval so as not to affect the appetite of the patient at dinner nor the patient's sleep thereafter. Excerpt(s): Sustained release dosage forms are central in the search for improved therapy, both through improved patient compliance and decreased incidences of adverse drug reactions. It is the intent of all sustained release formulations to provide a longer period of pharmacologic action after administration than is ordinarily obtained after administration of immediate-release dosage forms. Sustained release compositions may be used to delay absorption of a medicament until it has reached certain portions of the alimentary tract, and maintain a desired concentration of said medicament in the blood stream for a longer duration than would occur if conventional rapid release dosage forms are administered. Such longer periods of response provide for many therapeutic benefits that are not achieved with corresponding short acting, immediate release preparations. Thus, therapy may be continued without interrupting the sleep of the patient, which is of special importance, for example, when treating a patient for moderate to severe pain (e.g., a post-surgery patient, a cancer patient, etc.), or for those patients who experience migraine headaches on awakening, as well as for the debilitated patient for whom sleep is essential. A further general advantage of longer acting drug preparations is improved patient compliance resulting from the avoidance of missed doses through patient forgetfulness. Unless conventional rapid acting drug therapy is carefully administered at frequent intervals to maintain effective steady state blood levels of the drug, peaks and valleys in the blood level of the active drug occurs because of the rapid absorption, systemic excretion of the compound and through metabolic inactivation, thereby producing special problems in maintenance therapy of the patient. In view of this, it is considered a goal of many skilled in the art that a controlled release dosage form will ideally provide therapeutic concentration of the drug in blood that is maintained throughout the dosing interval with a reduction in the peak/trough concentration ratio. Central to the development process are the many variables that influence the in vivo release and subsequent absorption of the active ingredients from the gastrointestinal tract. It is known in the pharmaceutical art to prepare compositions which provide for sustained release of pharmacologically active substances contained in the compositions after oral administration to humans and animals. Sustained release formulations known in the art include specially coated pellets, coated tablets and capsules, and ion exchange resins, wherein the slow release of

Patents 43

the active medicament is brought about through selective breakdown of the coating of the preparation or through compounding with a special matrix to affect the release of a drug. Some sustained release formulations provide for related sequential release of a single dose of an active compound at predetermined periods after administration. Web site: http://www.delphion.com/details?pn=US06673367__ •

Method of treating attention deficit disorders with d-threo methylphenidate Inventor(s): Dariani; Maghsoud M. (Fanwood, NJ), Stirling; David I. (Branchburg, NJ), Zeitlin; Andrew L. (Millington, NJ) Assignee(s): Celgene Corporation (warren, Nj) Patent Number: 5,908,850 Date filed: April 2, 1997 Abstract: Methods for treating Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder, AIDS Dementia Complex and cognitive decline in HIV-AIDS while minimizing drug hypersensitivity, toxicity, side effects, euphoric effect, and drug abuse potential by administration of d-threo-methylphenidate or pharmaceutically acceptable salts thereof. Excerpt(s): The present invention relates to methods of treating certain Central Nervous System disorders such as Attention Deficit Disorder (ADD), Attention Deficit Hyperactivity Disorder (ADHD), HIV/AIDS cognitive decline, and AIDS Dementia Complex with decreased side effects, reduced euphoric effect, and reduced drug abuse potential. Attention Deficit Disorder (ADD) is the most commonly diagnosed illness in children. Patrick et al., J. Pharmacol. & Exp. Therap., 241:152-158 (1987). Symptoms of ADD include distractibility and impulsivity. A related disorder, termed Attention Deficit Hyperactivity Disorder (ADHD), is further characterized by increased symptoms of hyperactivity in patients. Racemic methylphenidate (e.g., Ritalin.RTM.) is a mild Central Nervous System stimulant with pharmacological activity qualitatively similar to amphetamines, and has been the drug of choice for symptomatic treatment of ADD in children. Greenhill, L., Child & Adol. Psych. Clin. N.A., Vol. 4, Number 1:123-165 (1995). Current administration of racemic methylphenidate, however, results in notable side effects such as anorexia, weight loss, insomnia, dizziness and dysphoria. Additionally, racemic methylphenidate which is a Schedule II controlled substance, produces a euphoric effect when administered intravenously or through inhalation, and thus carries a high potential for substance abuse in patients. At least 70% of HIV-infected individuals who have developed Acquired Immunodeficiency Syndrome (AIDS) eventually manifest cognitive defects, and many display signs and symptoms of dementia. See Navia et al., Annals of Neurology, 19:517-524 (1986). Complaints of forgetfulness, loss of concentration, fatigue, depression, loss of attentiveness, mood swings, personality change, and thought disturbance are common in patients with Human Immunodeficiency Virus (HIV) disease. Douzenis et al., Proc. 7th Int'l. Conf. AIDS, 1, MB, 2135:215 (1991); Holmes et al., J. Clin. Psychiatry, 50:5-8 (1989). Racemic methylphenidate has been used to treat cognitive decline in AIDS/ARC patients. Brown, G., Intl. J. Psych. Med. 25(1): 21-37 (1995). As described above, racemic methylphenidate which is a Schedule II controlled substance, produces a euphoric effect when administered intravenously or through inhalation, and thus carries a high potential for drug abuse in AIDS patients. Web site: http://www.delphion.com/details?pn=US05908850__

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Method of treating depression using 1-threo-methylphenidate Inventor(s): Kumar; Vijai (Morris Plains, NJ), Midha; Kamal K. (Hamilton, BM), Teicher; Martin (Waltham, MA) Assignee(s): Pharmaquest Limited (hamilton, Bm) Patent Number: 6,395,752 Date filed: August 11, 2000 Abstract: A method of treating dysphoria or depression is disclosed in a patient which comprises the step of administering orally or non-orally to said patient, a therapeutically effective amount of 1-threo-methylphenidate or a pharmaceutically acceptable acid addition salt thereof. Excerpt(s): This invention relates to a method of treating depression in a patient by oral or non-oral administration of 2S,2'S-methyl 2-phenyl-2-(2'-piperidyl) acetate, commonly known as 1-threo-methylphenidate, hereinafter referred to as 1-MPH and to pharmaceutical compositions containing 1-MPH designed to deliver 1-MPH to the central nervous system. More particularly the method of treatment is designed to provide relief to a depressed patient who is awaiting the onset of the antidepressive action of an antidepressant such as a selective serotonin re-uptake inhibitor, or any other class of antidepressant that requires administration over 2 to 6 weeks to demonstrate therapeutic effect. Orally administered racemic d1-threo-methylphenidate (d1-MPH) is widely used in the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in children and adults and also in the treatment of depression in patients suffering from cancer or AIDS, compulsive shopping disorder, narcolepsy, and hypersomnia. It is known that the therapeutic effect of d1-MPH in the treatment of ADHD in children is attributable to d-MPH (Srinivas et al, Clin. Pharmacol. Therap. 52, 561 to 568, 1992). Until recently, however, little was known about the potential pharmacological and/or therapeutic roles of 1-MPH because concentrations of 1-MPH in plasma and brain are very low due to extensive enantioselective first pass metabolism of 1-MPH after oral administration of d1-MPH (Srinivas et al, Pharm. Res. 10, 14 to 21, 1993). After intravenous administration of d1-MPH, however, both enantiomers of threomethylphenidate are taken up into the brain although their patterns of distribution are different (Ding et al, Psychopharmacology 131, 71 to 78, 1997). The use of oral stimulants such as dextroamphetamine or d1-MPH in the treatment of severe depressive disorders in the elderly or terminally ill depressed patients has been the subject of many studies over the years. After reviewing 85 publications on the subject, Satel and Nelson (J. Clin. Psychiat. 50, 241 to 249, 1989) were critical of the fact that many of the studies reported were methodologically unsophisticated and/or uncontrolled. They concluded that while stimulants are no more effective than a placebo in the treatment of primary depression, stimulants may be of value in the treatment of refractory patients and medically ill patients. Similarly, Chiarello and Cole (Arch. Gen. Psychiat. 44, 276 to 285, 1997) reviewed 81 publications and concluded that many of the older studies are inadequate although there was some evidence to support the use of psychostimulants in selected clinical instances. Emptage and Smith (Annals of Pharmacotherapy, 30, 151 to 157, 1996) reviewed 43 studies published from 1986 to 1995 and concluded that oral--MPH appears to be a safe and effective treatment for depressed, medically ill, elderly patients to provoke a rapid onset of antidepressant activity. Recently Wallace and co-workers (Am. J. Psychiat. 152, 929 to 931, 1995) conducted what they termed the first placebocontrolled double blind trial to demonstrate the efficacy of oral d1-MPH in older, medically ill depressed patients. The benefit of oral d1-MPH was statistically and clinically significant despite the small number of patients in the study (n=16).

Patents 45

Depressive symptoms decreased markedly in 7 subjects (Hamilton depression scale decreased by >55%), moderately in a further 3 subjects (Hamilton depression scale decreased by 30 to 55%), minimally in 3 subjects (Hamilton depression scale decreased by <30%) and three patients were dropped from the study. Web site: http://www.delphion.com/details?pn=US06395752__ •

Methylphenidate modified release formulations Inventor(s): Bettman; Marie J. (Clayton, OH), Hensley; Dan L. (Huber Heights, OH), Percel; Phillip J. (Troy, OH), Venkatesh; Gopi M. (Dayton, OH), Vishnupad; Krishna S. (Dayton, OH) Assignee(s): Eurand America, Inc. (vandalia, Oh) Patent Number: 6,344,215 Date filed: October 27, 2000 Abstract: A pharmaceutical MR (modified release) multiparticulate dosage form such as a capsule (once-a-day MR Capsule) of Methylphenidate indicated for the treatment of children with attention deficit hyperactivity disorder (ADHD), capable of delivering a portion of the dose for rapid onset of action and the remainder of the dose in a controlled manner for about 12 hours, is composed of a multitude of multicoated particles made of two populations of drug layered beads, IR (immediate release) and ER (extended release) Beads. The IR beads preferably are made by layering an aqueous solution comprising a drug and a binder on to non-pareil sugar spheres and then applying a seal coat to the drug coated cores. The ER Beads are made by applying an extended release coating of a water insoluble dissolution rate controlling polymer such as ethylcellulose to IR Beads. The MR Capsules are manufactured by filling IR and ER Beads in a proper ratio; the dose and the ratio required for an efficacious, cost effective and patient compliant treatment of children with ADHD were determined from extensive clinical investigations and in vitro- in vivo correlations performed as per FDA Guidelines, Guidance for Industry: Extended Release Oral Dosage Forms. Excerpt(s): Methylphenidate Hydrochloride, a scheduled II controlled substance, is currently marketed as a mild central nervous system (CNS) stimulant and the drug of choice for treatment of ADD and ADHA in children. The drug is well absorbed throughout the gastrointestinal tract. However, it has an extremely short half-life, which necessitates a multi-dose treatment regimen for conventional (immediate release) dosage forms such as currently available 5, 10, and 20 mg tablets. Due to high C.sub.max, oral administration of 10 and 20 mg Ritalin.RTM. is reported to result in notable side effects such as anorexia, weight loss, dizziness, etc. Furthermore, it requires the hyperactive children to be dosed in school thus causing hardship to school authorities as well as parents. The drawback of methylphenidate is that it also produces a euphoric effect when administered intravenously or through inhalation, thus presenting a high potential for substance abuse. Sustained release formulations for oncea-day dosing, such as 20 mg Ritalin SR.RTM. tablets currently available from Novartis and Geneva (generic version), were developed with the objective of providing efficacy for 8 hours, thereby improving compliance and reducing the incidence of diversion. However, there are reports which strongly suggest that the sustained release formulations exhibit a slower onset of action/efficacy compared to the immediate release dosage forms (W.E. Pelham et al., "Sustained Release And Standard Methylphenidate Effects On Cognitive And Social Behavior In Children With Attention Deficit Disorder," Pediatrics, Vol. 80, pp 491-501 (1987)). Recently, OROS.RTM.

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(methylphenidate HCl) has been approved by FDA. It is a new osmotic controlled release once-a-day oral dosage form with a drug overcoat, that is designed to deliver a portion of the dose for rapid onset of action and deliver the remainder of the dose in a controlled manner for about 10 hours. The manufacturing cost of this complicated dosage form is expected to be very high and hence resulting in a high cost of treatment. Hence, there is a dire need to develop modified release dosage forms with moderate cost of goods and having not only a rapid onset of action but also with a significantly longer duration of action. U.S. Pat. No. 5,908,850 assigned to Celgene Corporation discloses a method for treating children with the above disability to be treated using a sustained release dosage form containing d-threo-methylphenidate or pharmaceutically acceptable salts thereof thus minimizing hyperactivity and side effects. However, it does not address how it avoids dosing in school, thereby minimizing potential drug abuse. Web site: http://www.delphion.com/details?pn=US06344215__ •

Pharmaceutical dosage form for pulsatile delivery of d-threo-methylphenidate and a second CNS stimulant Inventor(s): Midha; Kamal K. (Hamilton, BM), Teicher; Martin H. (Waltham, MA) Assignee(s): Pharmaquest Ltd. (hamilton, Bm) Patent Number: 6,217,904 Date filed: April 6, 2000 Abstract: Novel pharmaceutical dosage forms provide for pulsatile delivery of d-threomethylphenidate and a second CNS stimulant, i.e., release encapsulated drug in spaced apart "pulses." The second CNS stimulant may be an analeptic agent or a psychostimulant, with analeptic agents preferred. The dosage forms may comprise capsules housing compressed tablets or drug-containing beads or particles, or may comprise a tablet with the first, second and optionally third dosage units each representing an integral and discrete segment thereof. Methods of treatment using the pharmaceutical dosage forms are provided as well. Excerpt(s): The present invention relates generally to drug delivery, and more specifically relates to novel pharmaceutical dosage forms that provide pulsatile delivery of d-threo-methylphenidate in combination with a second CNS stimulant. The invention additionally relates to methods for administering methylphenidate using the novel dosage forms. Pharmaceutical dosage forms are known which provide a variety of drug release profiles, including immediate release, sustained release, and delayed release. That is, it may be desirable, for a particular drug, to prevent drug release after drug administration until a certain amount of time has passed (so-called "timed release"), to provide substantially continuous release over a predetermined time period (so-called "sustained release") or to provide release immediately following drug administration (i.e., "immediate release"). For some types of drugs, it is preferred to release the drug in "pulses," wherein a single dosage form provides for an initial dose of drug followed by a release-free interval, after which a second dose of drug is released, followed by one or more additional release-free intervals and drug release "pulses." Pulsatile drug delivery is useful, for example, with active agents that have short half-lives and must be administered two or three times daily, with active agents that are extensively metabolized presystemically, and with active agents which lose the desired therapeutic effect when constant blood levels are maintained. These types of agents have pharmacokinetic-pharmacodynamic relationships that are best described by a clockwise "hysteresis loop." A drug dosage form that provides a pulsatile drug release profile is

Patents 47

also useful for minimizing the abuse potential of certain types of drugs, i.e., drugs for which tolerance, addiction and deliberate overdose can be problematic. Because a precise and effective pulsatile drug delivery system is difficult to formulate and manufacture, there are few such dosage forms that have been commercialized. There are, however, several patents and literature references pertaining to pulsatile drug delivery. See, for example, U.S. Pat. No. 5,413,777 to Sheth et al., directed to a pulsatile once-a-day delivery system for the administration of minocycline; U.S. Pat. No. 5,260,068 to Chen, directed to a multiparticulate pulsatile drug delivery system; U.S. Pat. No. 4,777,049 to Magruder et al., directed to an osmotic delivery system for constant release of a drug with intermittent release "pulses"; U.S. Pat. No. 5,391,381 to Wong et al., directed to a drug dispenser for delivering individual drug-containing units in a "pulsatile" manner; PCT Publication No. WO 98/32424, pertaining to pulsatile delivery of diltiazem hydrochloride; U.S. Pat. Nos. 5,472,708 and 5,260,069 to Chen; Ishino et al. (1992) "Design and Preparation of Pulsatile Release Tablet as a New Oral Drug Delivery System," Chem. Pharm. Bull. 40(11):3036-3041; Cohen et al. (1994), "Pulsatile Release from Microencapsulated Liposomes," J. Liposome Res. 349-360; and Gazzaniga et al. (1994), "Chronotopic Drug Delivery Systems for Pulsatile and/or Site-Specific Release," 21.sup.st. Proc. Int. Symp. Controlled Release Bioact. Mater., pp. 744-745. Web site: http://www.delphion.com/details?pn=US06217904__ •

Process for preparing the d-threo isomer of methylphenidate hydrochloride Inventor(s): Har; Denis (Harrison, NJ), Prashad; Mahavir (Montville, NJ) Assignee(s): Novartris AG (basel, Ch) Patent Number: 6,100,401 Date filed: April 20, 1998 Abstract: A process for preparing the d-threo isomer of methylphenidate hydrochloride comprising resolving the racemic mixture of threo methylphenidate hydrochloride with dibenzoyl-D-tartaric acid to obtain a dibenzoyl-D-tartrate salt enriched with the d-threo isomer of methylphenidate in a first step, basifying the tartrate salt to obtain the free base form of the d-threo isomer of methylphenidate in a second step, converting the free base to the hydrochloride salt form of the d-threo isomer of methylphenidate in high optical purity in a third step, and recrystallizing the hydrochloride salt form to obtain the desired d-threo isomer in a higher optical purity. Excerpt(s): The present invention relates to the area of resolution processes and, more particularly, relates to an improved process for preparing the d-threo isomer of methylphenidate hydrochloride employing dibenzoyl-D-tartaric acid as the resolving agent. Methylphenidate was first prepared as a mixture of the erythro and threo racemates. Subsequent studies of the two racemic mixtures revealed that the therapeutic activity resides in the threo diastereomer. Racemic threo methylphenidate hydrochloride is a mild nervous system stimulant which is marketed for the treatment of children with Attention Deficit Hyperactivity Disorder (ADHD). Further studies of the threo diastereomer revealed that the preferred therapeutic activity resides in the dthreo (or 2R,2'R enantiomer. More particularly, it has been found that the d-threo enantiomer is between five and thirty-eight times more active then the corresponding lthreo enantiomer. In addition, it has been shown that there are significant metabilic differences between the two enantiomers. Web site: http://www.delphion.com/details?pn=US06100401__

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Resolution of threo-methylphenidate Inventor(s): Zavareh; Hooshang Shahriari (Cambridge, GB) Assignee(s): Medeva Europe Limited (gb) Patent Number: 6,121,453 Date filed: September 8, 1998 Abstract: A process for preparing substantially single enantiomer d-threomethylphenidate, proceeds by means of a classical salt resolution using (-)menthoxyacetic acid. Excerpt(s): This invention relates to the resolution of threo methylphenidate via crystallisation of diastereomeric salts. Methylphenidate was first prepared as a mixture of the erythro and threo racemates. U.S. Pat. No. 2,957,880 discloses studies upon the two racemic mixtures, which revealed that the therapeutic activity resides in the threo diastereomer. The resolution of threo methylphenidate can be achieved using the expensive resolving agent 1,1'-binaphthyl-2,2'-diylhydrogen phosphate, a process first reported by Patrick et al (The Journal of Pharmacology and Experimental Therapeutics, 241:152-158 (1987)), and subsequently used by other workers in the field (e.g. Aoyama et al, Journal of Chromatography, 494:420 (1989)). This is perceived to be a more efficient procedure than the method disclosed in U.S. Pat. No. 2,957,880, wherein the corresponding amide of erythro methylphenidate (i.e. R--CONR.sub.2 rather than R-CON.sub.2 Me) is resolved with tartaric acid prior to amide hydrolysis and equilibration at the benzylic centre, followed by esterification of the resultant threo-acid. Web site: http://www.delphion.com/details?pn=US06121453__

Patent Applications on Concerta As of December 2000, U.S. patent applications are open to public viewing.7 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 Concerta: •

Composition comprising methylphenidate and another drug Inventor(s): Pope, Nicholas Robert; (Cambridge, GB), Richards, Andrew John McGlashan; (Cambridge, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030049205 Date filed: October 21, 2002 Abstract: A process of treating a subject that is undergoing methylphenidate therapy and concomitant therapy with another drug undergoes or interferes with P.sub.450 metabolism, wherein the methylphenidate is d-threo-methylphenidate. Excerpt(s): This invention relates to a new composition comprising methylphenidate and another drug, and also to new ways or using known drugs including d-threo-

7

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

Patents 49

methylphenidate (abbreviated herein as dtmp). Methylphenidate is a known drug (although it is a controlled substance). It is used primarily to treat hyperactive children. Methylphenidate is a chiral molecule. The properties of the enantiomers have been investigated to some extent, although the drug is still administered as the racemate. It is generally thought that dtmp is the active material, and that its antipode (ltmp) is metabolized more rapidly. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and method for treatment of attention deficit disorder and attention deficit/hyperactivity disorder with methylphenidate Inventor(s): Dixon, Terese A.; (Miami, FL), Mantelle, Juan; (Miami, FL) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20020102291 Date filed: December 21, 2001 Abstract: The invention relates to a method of treating Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) and compositions for topical application of methylphenidate comprising methylphenidate in a flexible, finite system wherein said composition comprises about 10 to 30 wt % methylphenidate, about 30 to 50 wt % acrylic adhesive, and about 30 to 50 wt % silicone adhesive and wherein said methylphenidate is delivered to a subject in need thereof such that the plasma concentration of methylphenidate increases over a period of about 6-16 hours, and more preferably over a period of about 6-12 hours followed by a steady decrease in plasma concentration of methylphenidate. Excerpt(s): This application is a continuation in part of U.S. patent application Ser. No. 09/618,626, filed Jul. 18, 2000, which is a Divisional Application of U.S. patent application Ser. No. 09/163,351, filed Sep. 30, 1998, now U.S. Pat. No. 6,210,705, which claims the benefit of U.S. provisional Application Ser. No. 60/069,510, filed Dec. 15, 1997, now abandoned. These applications are hereby incorporated by reference in their entirety. The present invention relates to compositions and methods for the treatment of Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) by means of topical application of methylphenidate. Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) (severally and collectively hereinafter referred to as "AD") are developmental disorders of self-control. They consist of problems with attention span, impulse control, and activity level. These problems are reflected in impairment of a person's will or capacity to control his or her own behavior relative to the passage of time and to keep future goals and consequences in mind. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Manufacture of single isomer methylphenidate Inventor(s): Langston, Marianne; (Cambridge, GB), Zavareh, Hooshang Shahriari; (Cambridge, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20020032335 Date filed: August 10, 2001 Abstract: The present invention pertains to a process for obtaining a single enantiomer, d or l, of threo-methylphenidate, comprising resolution of a mixture of the enantiomers; racemisation of the unwanted enantiomer, to give a mixture of all four stereoisomers; and separation of the erythro stereoisomers, to leave the same mixture of enantiomers for resolution. Excerpt(s): This invention relates to an economic process for the manufacture of a single isomer of methylphenidate. Methylphenidate is a therapeutic agent that is widely used in the treatment of attention-deficit hyperactivity disorder. It is a controlled substance. Methylphenidate was first prepared as a mixture of the erythro [R*S*] and threo [R*R*] racemates U.S. Pat. No. 2,957,880 discloses studies upon the two racemic mixtures, which revealed that the therapeutic activity resides in the threo diastereoisomer. It is now considered that it is the d-threo [or (R,R)] enantiomer that has the preferred therapeutic activity. Uses of this enantiomer are disclosed in PCT/GB96/01688 PCT/GB96/01689 and PCT/GB96/01690, the contents of which are incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Method for preventing abuse of methylphenidate Inventor(s): Midha, Kamal K.; (Hamilton, BM) Correspondence: Reed & Eberle Llp; 800 Menlo Avenue, Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20030170181 Date filed: December 16, 2002 Abstract: A method is provided for treating a patient with a methylphenidate-responsive condition that is at a risk of abusing or becoming addicted to methylphenidate. The patient is first evaluated for an elevated risk of drug abuse or addiction through psychological evaluations and then treated with a methylphenidate product that includes an emesis-inducing agent that is inert when ingested orally and only produces emesis when snorted or taken intravenously or a topical analgesic that is inert when ingested orally and only produces irritation when snorted or taken intravenously. The method includes delivering the methylphenidate in a pulsatile delivery system such that the emesis-inducing agent or the topical analgesic is included in one of the pulsatile dosages. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/992,353, filed Nov. 13, 2001, which is a continuation of U.S. patent application Ser. No. 09/544,732, filed Apr. 6, 2000, and issued as U.S. Pat. No. 6,340,476 on Jan. 22, 2002, which claimed priority under 35 U.S.C.sctn.119(e)(1) to U.S. Provisional Patent Application Serial No. 60/127,984, filed Apr. 6, 1999. The disclosures of the

Patents 51

aforementioned patent applications are incorporated by reference herein. The present invention relates generally to the fields of drug delivery, pharmacology, and medicine. More specifically, the invention relates to a method of reducing the likelihood of abuse of methylphenidate by administering a methylphenidate product that is formulated to prevent abuse of the drug. The methylphenidate product may be administered to the patient via a pulsatile drug release system. The drug as used in therapy is a racemic mixture of the d- and l-threo enantiomers, which have been acknowledged as more active than the erythro pair. The racemic d,l-threo methylphenidate (hereinafter referred to as "methylphenidate," "d,l-MPH," or "MPH") is a short-acting stimulant with a duration of action of one to four hours and a pharmacokinetic elimination half-life of two to three hours. Maximum drug concentration after oral administration occurs at about two hours, at which time, the methylphenidate has been absorbed from the gastrointestinal tract and has passed into the systemic circulation including the brain. It is believed that once in the brain, methylphenidate influences neurotransmitters by inhibiting the uptake of dopamine in the striatum. Kimko, H. C., et al., "Pharmacokinetics and Clinical Effectiveness of Methylphenidate," Clinical Pharmacokinetics 37(b):457-470 (December, 1999). The therapeutic dosage for methylphenidate is typically very low with tablets being dispensed in 5 mg, 10 mg, and 20 mg dosages, concentrations often referred to as "microdoses." Side effects of the drug in its therapeutic dosages include anorexia, weight loss, insomnia, dizziness, and dysphoria. See, e.g., U.S. Pat. No. 6,410,746 to Davies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate Inventor(s): Faleck, Herbert; (West Orange, NJ), Khetani, Vikram; (Jersey City, NJ), Zeldis, Jerome B.; (Princeton, NJ) Correspondence: Woodcock Washburn Kurtz; Mackiewicz & Norris Llp; One Liberty Place - 46th Floor; Philadelphia; PA; 19103; US Patent Application Number: 20020022640 Date filed: July 12, 2001 Excerpt(s): This application is a continuation in part of U.S. Ser. No. 09/318,151, filed May 25, 1999, which is a continuation in part of U.S. Ser. No. 08/583,317 filed Jan. 5, 1996, now U.S. Pat. No. 5,773,756, and a continuation in part of U.S. Ser. No. 08/827,230, filed Apr. 2, 1997, now U.S. Pat. No. 5,908,850, which is continuation of U.S. Ser. No. 08/567,131, filed Dec. 4, 1995. The contents of each of the foregoing applications are incorporated herein by reference in their entirety. In one aspect, the present invention is directed to methods for treating fatigue, neurobehavioral slowing and other cognitive disorders and defects due to cancers and treatments associated with cancers, and similar conditions. In a further aspect, the present invention is directed to methods for treating disorders related to menopause, including executive function defects. The methods involve the administration of a composition comprising D-threo methylphenidate that is substantially free of L-threo methylphenidate and of erythro forms of methylphenidate. Advanced cancer typically produces severe pain in patients. This pain is often controlled by the administration of large doses of analgesics, including opioid analgesics. However, the pain relief is often accompanied by undesirable sideeffects such as unacceptable sedation and/or a decrease in cognitive function. These side effects have a significant negative impact on the quality of life of the patient. In addition,

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cancer patients often display one or more of a decrease in cognitive function, fatigue, and neurobehavioral slowing that is unrelated to the administration of analgesics, but may be related to the underlying cancer, the treatment of the cancer, or both. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical dosage form for pulsatile delivery of methylphenidate Inventor(s): Chungi, Shubha; (Sharon, MA), Iorio, Theodore L.; (Millis, MA), Midha, Kamal K.; (Hamilton, CA) Correspondence: Reed & Associates; 800 Menlo Avenue; Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20020058061 Date filed: November 13, 2001 Abstract: Novel pharmaceutical dosage forms provide for pulsatile delivery of methylphenidate, i.e., release encapsulated drug in spaced apart "pulses." The dosage forms are comprised of first, second and optionally third dosage units, with each dosage unit having a different drug release profile. The dosage forms may comprise capsules housing compressed tablets or drug-containing beads or particles, or may comprise a single tablet with the first, second and optionally third dosage units each representing an integral and discrete segment thereof. Methods of treatment using the pharmaceutical dosage forms are provided as well. Excerpt(s): This application claims priority to U.S. Provisional Patent Application Ser. No. 60/127,984, filed Apr. 6, 1999. The present invention relates generally to drug delivery, and more specifically relates to novel pharmaceutical dosage forms that provide pulsatile delivery of methylphenidate. The invention additionally relates to methods for administering methylphenidate using the novel dosage forms. Pharmaceutical dosage forms are known which provide a variety of drug release profiles, including immediate release, sustained release, and delayed release. That is, it may be desirable, for a particular drug, to prevent drug release after drug administration until a certain amount of time has passed (so-called "timed release"), to provide substantially continuous release over a predetermined time period (so-called "sustained release") or to provide release immediately following drug administration (i.e., "immediate release"). For some types of drugs, it is preferred to release the drug in "pulses," wherein a single dosage form provides for an initial dose of drug followed by a release-free interval, after which a second dose of drug is released, followed by one or more additional release-free intervals and drug release "pulses." Pulsatile drug delivery is useful, for example, with active agents that have short half-lives and must be administered two or three times daily, with active agents that are extensively metabolized presystemically, and with active agents which lose the desired therapeutic effect when constant blood levels are maintained. These types of agents have pharmacokinetic-pharmacodynamic relationships that are best described by a clockwise "hysteresis loop." A drug dosage form that provides a pulsatile drug release profile is also useful for minimizing the abuse potential of certain types of drugs, i.e., drugs for which tolerance, addiction and deliberate overdose can be problematic. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Pulse dosage formulations of methylphenidate and method to prepare same Inventor(s): Krsek, George; (Tucson, AZ) Correspondence: Dale F. Regelman; Hayes, Soloway, Hennessey,; Grossman, & Hage, P.C.; 130 W. Cushing Street; Tucson; AZ; 85701; US Patent Application Number: 20030129229 Date filed: January 3, 2002 Abstract: Dosage forms comprising pulse release formulations for oral administration of a Methylphenidate drug are provided. The dosage forms provide a substantially immediate dose of methylphenidate upon ingestion, followed by one or more additional doses at predetermined times. By providing such a drug release profile, the dosage forms eliminate the need for a patient to carry an additional dose for ingestion during the day. The dosage forms and methods provided are useful in administering Methylphenidate and pharmaceutically acceptable salts thereof, which generally require one or more doses throughout the day. Excerpt(s): Applicant's invention relates to improved dosing of medications. In particular, the present invention relates to improved dosing of a medication whereby two or more effective pulse dosages may be provided by administration of a pulse release formulation. Effective administration of the second pulse dosage is time-delayed following oral ingestion of Applicant's pulse release formulation. Applicant's dosage forms and methods are particularly suitable for the administration of methylphenidate hydrochloride, and especially for the administration of a single isomer, d-threomethylphenidate hydrochloride ("DTMP"). Applicant's method of administration of a pulse release formulation which contains a first pulse release dosage in combination with a second pulse release dosage provides for reduced abuse potential, improved convenience of administration, and better patient compliance, especially when methylphenidate is used to treat certain central nervous system disorders. Attention Deficit Disorder (ADD), a commonly diagnosed nervous system illness in children, is often treated with methylphenidate hydrochloride. Methylphenidate is sold in commerce under the name Ritalin.RTM. Ritalin is a registered trademark owned by Novartis Corporation. 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 Concerta, 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 “Concerta” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on Concerta. You can also use this procedure to view pending patent applications concerning Concerta. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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APPENDICES

57

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 Institute8: •

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/

8

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.9 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:10 •

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

9

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

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•

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

•

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

The NLM Gateway11 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.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Concerta” (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 17 0 981 0 0 998

HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 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.15 Simply search by “Concerta” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

11

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

12

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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15

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

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

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Coffee Break: Tutorials for Biologists16 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.17 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.18 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/.

16 Adapted 17

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. 18 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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

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•

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Other guides Attention Deficit Disorder with Hyperactivity http://www.nlm.nih.gov/medlineplus/attentiondeficitdisorderwithhyperactivity.t ml Child Mental Health http://www.nlm.nih.gov/medlineplus/childmentalhealth.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.html Tourette Syndrome http://www.nlm.nih.gov/medlineplus/tourettesyndrome.html Tuberous Sclerosis http://www.nlm.nih.gov/medlineplus/tuberoussclerosis.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Concerta. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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/

Patient Resources

•

65

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

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

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.19

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

19

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)20: •

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/

20

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

Finding Medical Libraries

69

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

75

CONCERTA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [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] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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

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substances. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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]

Dictionary

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Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Aqueous: Having to do with water. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH]

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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] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]

Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been

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observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing

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acetylcholine or a related compound. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] 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] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy,

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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] Concomitant: Accompanying; accessory; joined with another. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [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] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline

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is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [NIH]

Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized formulation is dispensed; an instrument for atomizing. [NIH] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] 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]

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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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [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] Drug Hypersensitivity: Immunologically mediated adverse reactions to medicinal substances used legally or illegally. [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] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]

Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoria: Disquiet; restlessness; malaise. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain

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microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [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] 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] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

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

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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] Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanfacine: A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [NIH] Haematemesis: The vomiting of blood. [EU] 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] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the

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prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [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]

Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH]

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

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique

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is used in water purification, in research, and in industry. [NIH] Ion Exchange Resins: High molecular weight, insoluble polymers which contain functional groups that are capable of undergoing exchange reactions (ion exchange) with either cations or anions. [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] 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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [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] 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.

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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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mazindol: Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [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] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH]

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Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [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] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

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] 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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of

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a single species of immunoglobulin molecules. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motility: The ability to move spontaneously. [EU] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH]

Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [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] 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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]

Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

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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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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

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molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [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] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [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] Phenyl: Ingredient used in cold and flu remedies. [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]

Pilot study: The initial study examining a new method or treatment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]

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Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] 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] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]

Psychotomimetic: Psychosis miming. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH]

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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]

Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]

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Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritalin: Drug used to treat hyperactive children. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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] 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] Small intestine: The part of the digestive tract that is located between the stomach and the

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large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] 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] 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] Steady state: Dynamic equilibrium. [EU] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between

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the termination of the esophagus and the beginning of the duodenum. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [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] 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] 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] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [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

Dictionary

99

synthesis. [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] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] 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] Topical: On the surface of the body. [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] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] 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] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin

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damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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] 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] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] 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] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

101

INDEX A Acquired Immunodeficiency Syndrome, 40, 43, 75 Acyl, 75, 84 Adaptation, 75, 93 Adenosine, 75, 79 Adjustment, 19, 75 Adjuvant, 25, 75 Adrenal Medulla, 75, 79, 84, 92 Adrenergic, 75, 83, 84, 98 Adverse Effect, 75, 96 Affinity, 75, 82, 97 Agonist, 75, 78, 83, 92 Alertness, 76, 78 Algorithms, 11, 76 Alimentary, 42, 76, 87 Alkaloid, 76, 78, 80, 91, 92 Allergen, 76, 96 Alpha Particles, 76, 95 Alternative medicine, 76 Amenorrhea, 76, 78 Amino acid, 76, 82, 94, 96, 99 Amphetamine, 14, 23, 33, 41, 76, 82, 89 Analeptic, 46, 76 Analgesic, 22, 50, 76, 91 Anaphylatoxins, 76, 80 Anatomical, 76, 79, 86 Anesthetics, 76, 84 Anions, 77, 88 Anorexia, 43, 45, 51, 77 Antagonism, 77, 79, 82 Antibiotic, 77, 90, 98 Antibody, 75, 77, 80, 86, 87, 89, 90, 95, 96 Anticonvulsant, 77, 100 Antidepressant, 44, 77, 80, 100 Antigen, 75, 77, 80, 86, 87, 89, 96 Antigen-Antibody Complex, 77, 80 Antihypertensive, 77, 85 Apathy, 14, 77 Aqueous, 45, 77, 88 Arteries, 77, 78, 81, 90 Artery, 77, 81, 82, 95 B Base, 47, 77, 88 Bioavailability, 13, 77 Biochemical, 77, 96 Biological response modifier, 77, 87 Bipolar Disorder, 24, 77

Bladder, 77, 81, 100 Blood Platelets, 78, 96, 99 Blood pressure, 9, 77, 78, 97 Blood vessel, 78, 79, 89, 97, 98, 99, 100 Body Fluids, 78, 97 Bolus, 40, 78 Bolus infusion, 78 Bone Marrow, 78, 86, 88, 97 Bowel, 78, 82 Bowel Movement, 78, 82 Brachytherapy, 78, 87, 95 Brain Injuries, 35, 78 Brain metastases, 34, 78 Brain Stem, 78, 79 Branch, 71, 78, 89, 92, 94, 97 Breakdown, 43, 78, 82 Bromocriptine, 24, 78 Bronchi, 78, 84 C Caffeine, 23, 76, 78 Calcium, 79, 80, 82 Capsules, 42, 45, 46, 52, 79, 83 Cardiac, 78, 79, 84, 91 Cardiovascular, 6, 76, 79, 96 Case report, 24, 79, 80 Catecholamine, 79, 83 Cations, 79, 88 Cell, 24, 75, 76, 79, 80, 82, 83, 84, 86, 87, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 Central Nervous System, 33, 41, 43, 44, 45, 53, 76, 78, 79, 80, 82, 85, 88, 90, 91, 93, 96 Cerebellar, 9, 79 Cerebellum, 78, 79, 85 Cerebral, 8, 9, 10, 18, 78, 79, 84, 85, 94, 98 Cerebral hemispheres, 78, 79 Cerebral Palsy, 10, 79 Cerebrum, 79 Chemotactic Factors, 79, 80 Chemotherapy, 34, 79 Chin, 79, 90 Cholinergic, 79, 92 Chronic, 3, 22, 23, 40, 78, 80, 87 Citalopram, 7, 80 Clinical study, 80, 81 Clinical trial, 3, 4, 33, 36, 59, 80, 83, 94, 95 Coca, 80 Cocaine, 8, 19, 22, 23, 24, 35, 80, 89 Collapse, 78, 80

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Complement, 4, 76, 80, 81, 96 Complementary and alternative medicine, 27, 28, 80 Complementary medicine, 27, 81 Compliance, 42, 45, 81 Computational Biology, 59, 81 Concomitant, 48, 81 Conjugated, 81 Consciousness, 76, 81, 82, 98 Constipation, 81, 85 Contraindications, ii, 81 Controlled clinical trial, 4, 81 Coronary, 81, 90 Coronary Thrombosis, 81, 90 Cortical, 81, 91, 96 Cyclic, 79, 81, 96 Cytochrome, 13, 81 D Dehydroepiandrosterone, 19, 81 Dementia, 43, 75, 81, 82 Dendrites, 82, 92 Depressive Disorder, 44, 82, 88 Desipramine, 9, 82 Dextroamphetamine, 33, 44, 76, 82, 90 Diagnostic procedure, 39, 82 Diaphragm, 82, 86 Diastolic, 82, 85 Diastolic blood pressure, 82, 85 Diffuse Axonal Injury, 78, 82 Digestion, 76, 78, 82, 88, 97 Digestive system, 36, 82 Diltiazem, 47, 82 Direct, iii, 82, 83, 95, 98 Discrete, 46, 52, 82 Dispenser, 47, 82 Diuresis, 78, 82 Dizziness, 43, 45, 51, 82 Dopa, 9, 82, 88 Dopamine, 6, 8, 10, 13, 14, 18, 19, 22, 23, 24, 51, 76, 78, 80, 82, 83, 88, 89, 90, 92 Dosage Forms, 42, 45, 46, 52, 53, 83 Double-blind, 5, 8, 83 Drug Hypersensitivity, 43, 83 Drug Tolerance, 83, 99 Duke, 23, 83 Dyskinesia, 12, 80, 83 Dysphoria, 43, 44, 51, 83 Dysphoric, 82, 83 E Effector, 80, 83 Effector cell, 83 Efficacy, 7, 10, 19, 34, 35, 44, 45, 83

Electrolyte, 83, 97 Emaciation, 75, 83 Emesis, 50, 83 Encapsulated, 46, 52, 83 Endogenous, 83 Endotoxins, 80, 83 Environmental Health, 58, 60, 84 Enzymatic, 76, 79, 80, 84 Epinephrine, 6, 75, 83, 84, 92, 99 Ergot, 78, 84 Erythrocytes, 78, 84, 96 Esophagus, 82, 84, 98 Esterification, 48, 84 Ethanol, 80, 84 Excitability, 12, 84, 91 External-beam radiation, 84, 95 Extracellular, 14, 84, 97 Extrapyramidal, 83, 84 F Family Planning, 59, 84 Fatigue, 12, 16, 34, 35, 43, 51, 84, 93 Fixation, 84, 96 Forearm, 78, 85 Fourth Ventricle, 85, 88 Frontal Lobe, 85, 91 G Gallbladder, 82, 85 Gamma Rays, 85, 95 Ganglia, 85, 91 Gastric, 83, 85 Gastrin, 85, 86 Gastrointestinal, 42, 45, 51, 84, 85, 96 Gastrointestinal tract, 42, 45, 51, 84, 85, 96 Gene, 8, 85, 93 Glottis, 85, 86 Governing Board, 85, 94 Growth, 7, 24, 77, 85, 87, 89, 91, 93, 96, 99 Guanfacine, 34, 85 H Haematemesis, 83, 85 Half-Life, 45, 51, 85 Headache, 78, 85 Heme, 81, 85 Hemiparesis, 78, 86 Hemorrhage, 85, 86, 98 Hemostasis, 86, 96 Heredity, 85, 86 Hiccup, 18, 86 Homologous, 86, 96, 98 Hormone, 24, 84, 85, 86, 94, 96 Hydrogen, 77, 86, 90, 92, 94 Hydrolysis, 48, 86, 94

Index

Hypersensitivity, 76, 86, 96 Hypothalamic, 24, 86 Hypothalamus, 86 I Id, 26, 27, 64, 70, 72, 86 Immune response, 75, 77, 86, 96, 100 Immune system, 83, 86, 89, 91, 100 Immunity, 75, 86 Immunization, 86, 96 Immunodeficiency, 41, 43, 75, 86 Immunology, 75, 86 Impairment, 41, 49, 83, 86, 90 Implant radiation, 87, 95 In vitro, 45, 87 In vivo, 24, 42, 45, 87 Infarction, 81, 87, 90 Infection, 75, 77, 79, 86, 87, 88, 89, 92, 98 Infertility, 78, 87 Ingestion, 53, 87 Inhalation, 43, 45, 86, 87 Inotropic, 83, 87 Inpatients, 9, 87 Insomnia, 43, 51, 87 Interferon, 12, 35, 87 Interferon-alpha, 87 Intermittent, 47, 87 Internal radiation, 87, 95 Intestines, 85, 87 Intracellular, 79, 87, 95, 96 Intravenous, 22, 23, 44, 87 Ion Channels, 87, 98 Ion Exchange, 42, 87, 88 Ion Exchange Resins, 42, 88 Ions, 77, 83, 86, 87, 88, 97 K Kb, 58, 88 Kinetic, 19, 88 L Labile, 80, 88 Large Intestine, 82, 87, 88, 95, 97 Lens, 88, 96 Levodopa, 82, 88 Library Services, 70, 88 Lithium, 5, 25, 88 Liver, 82, 85, 88, 90 Localized, 78, 83, 85, 87, 88, 90, 93 Locomotion, 88, 93 Locomotor, 22, 23, 24, 88 Locus Coeruleus, 9, 88 Loop, 46, 52, 88 Lymphatic, 87, 88, 97 Lymphatic system, 88, 97

103

Lymphocyte, 75, 77, 89 Lymphocyte Count, 75, 89 M Maintenance therapy, 42, 89 Malaise, 83, 89 Malignant, 75, 89, 91, 95 Mania, 89 Manic, 17, 77, 88, 89 Manifest, 43, 89 Mazindol, 22, 89 Mediate, 83, 89 Mediator, 82, 89, 96 Medicament, 42, 89 MEDLINE, 59, 89 Meiosis, 89, 98 Melanin, 88, 89, 99 Melanocytes, 89 Melanoma, 12, 34, 89, 99 Membrane, 80, 82, 84, 87, 89, 91, 92, 97 Memory, 33, 35, 77, 81, 89 Meninges, 79, 89 Menopause, 51, 89 Menstruation, 76, 89 Mental, iv, 3, 14, 19, 22, 34, 37, 58, 60, 64, 79, 81, 84, 89, 90, 94 Mental Disorders, 37, 90, 94 Mental Health, iv, 3, 22, 34, 37, 58, 60, 64, 90, 94 Mental Retardation, 14, 19, 90 Mesencephalic, 88, 90 Meta-Analysis, 7, 90 Metastasis, 90, 91 Metastatic, 34, 90 MI, 73, 90 Microbe, 90, 99 Minocycline, 47, 90 Modification, 76, 90, 95 Molecular, 18, 59, 61, 81, 88, 90, 94, 95, 99 Molecule, 49, 77, 80, 83, 86, 90, 92, 95 Monoamine, 76, 82, 90 Monoamine Oxidase, 76, 82, 90 Monoclonal, 90, 95 Morphine, 91 Motility, 91, 96 Motor Cortex, 13, 91 Mucosa, 41, 91, 94 Myocardium, 90, 91 N Naive, 10, 91 Narcolepsy, 44, 82, 90, 91 Narcosis, 91 Narcotic, 25, 91

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Nausea, 83, 91 NCI, 1, 33, 34, 36, 57, 91 Need, 35, 41, 46, 49, 53, 65, 91, 99 Neonatal, 25, 91 Neoplasms, 75, 91, 95 Nerve, 75, 79, 82, 88, 89, 90, 91, 93, 97, 99 Nervous System, 40, 43, 47, 53, 76, 79, 89, 91, 92, 98 Neural, 10, 82, 90, 91, 97 Neurobehavioral Manifestations, 78, 82, 91 Neurologic, 78, 91 Neuronal, 19, 80, 91 Neurons, 9, 80, 82, 85, 88, 91, 92, 98 Neurotoxicity, 33, 92 Neurotransmitter, 75, 76, 83, 87, 92, 96, 98 Neutrons, 76, 92, 95 Nicotine, 23, 92 Norepinephrine, 75, 82, 83, 92 Nucleus, 81, 85, 88, 89, 92, 94 O Ointments, 83, 92 Ophthalmologic, 83, 92 Opportunistic Infections, 75, 92 Orofacial, 12, 92 Osmosis, 92 Osmotic, 23, 46, 47, 92 Overdose, 47, 52, 92 Oxidation, 81, 92 P Pancreas, 82, 93 Patient Compliance, 42, 53, 93 Pemoline, 24, 93 Pharmaceutical Solutions, 83, 93 Pharmacokinetic, 46, 51, 52, 93 Pharmacologic, 42, 85, 93, 99 Phenyl, 44, 93 Physiologic, 75, 82, 85, 89, 93, 95 Pilot study, 8, 12, 34, 93 Plants, 76, 80, 92, 93, 99 Plasma, 6, 19, 44, 49, 86, 93 Plasticity, 15, 93 Platinum, 88, 93 Pneumonia, 81, 93 Polymers, 88, 93, 94 Postsynaptic, 9, 93, 98 Post-traumatic, 78, 93 Potentiates, 82, 93 Potentiation, 14, 93 Practice Guidelines, 60, 94 Precursor, 82, 83, 84, 88, 92, 94, 99 Prevalence, 11, 16, 94

Progressive, 82, 83, 85, 94 Prolactin, 78, 94 Prophase, 94, 98 Proteins, 76, 77, 80, 90, 93, 94, 95, 96 Proteolytic, 80, 94 Protocol, 30, 33, 34, 94 Protons, 76, 86, 94, 95 Psychiatric, 3, 90, 94 Psychiatry, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 19, 20, 22, 23, 25, 41, 43, 84, 94, 98 Psychic, 90, 94, 96 Psychomotor, 7, 94 Psychopathology, 4, 94 Psychopharmacology, 4, 6, 7, 8, 11, 12, 14, 15, 17, 19, 22, 23, 25, 44, 94 Psychotomimetic, 76, 82, 94 Public Health, 4, 22, 60, 94 Public Policy, 59, 95 Pulmonary, 78, 95, 100 Pulmonary Artery, 78, 95, 100 Pulse, 53, 95 Q Quality of Life, 34, 51, 95 R Race, 40, 43, 44, 47, 48, 50, 51, 82, 95 Racemic, 40, 43, 44, 47, 48, 50, 51, 82, 95 Radiation, 34, 84, 85, 87, 95, 99, 100 Radiation therapy, 34, 84, 87, 95 Radioactive, 85, 86, 87, 95 Radiolabeled, 95 Radiotherapy, 78, 95 Randomized, 4, 5, 6, 16, 35, 83, 95 Reaction Time, 35, 95 Receptor, 13, 22, 75, 77, 83, 95, 96 Receptors, Serotonin, 95, 96 Rectum, 78, 82, 88, 95 Recurrence, 77, 95 Refer, 1, 80, 82, 84, 88, 91, 92, 95, 99 Refractory, 25, 44, 95 Regimen, 45, 83, 93, 95 Remission, 77, 89, 95, 96 Research Design, 4, 96 Resolving, 47, 48, 96 Risk factor, 11, 96 Ritalin, 7, 10, 12, 15, 19, 29, 34, 41, 43, 45, 53, 96 S Salivary, 82, 96 Salivary glands, 82, 96 Screening, 80, 96 Second Messenger Systems, 96 Secretion, 78, 96

Index

Seizures, 3, 6, 18, 96 Semisynthetic, 78, 90, 96 Sensitization, 24, 96 Serotonin, 44, 80, 82, 90, 92, 95, 96, 99 Serum, 18, 76, 80, 96 Side effect, 6, 34, 35, 40, 43, 45, 51, 75, 80, 89, 96, 99 Signs and Symptoms, 43, 96 Small intestine, 86, 87, 96 Smooth muscle, 76, 78, 91, 97 Social Environment, 95, 97 Sodium, 25, 97, 100 Sodium Channels, 97, 100 Solid tumor, 33, 34, 97 Solvent, 84, 92, 93, 97 Soma, 97 Somatic, 6, 89, 97 Spasm, 86, 90, 97 Spatial disorientation, 82, 97 Specialist, 65, 97 Species, 84, 89, 91, 95, 97, 100 Spinal cord, 78, 79, 89, 91, 97 Staphylococcus, 90, 97 Steady state, 42, 97 Steroids, 81, 97 Stimulant, 33, 34, 41, 43, 45, 46, 47, 51, 76, 78, 82, 90, 93, 97 Stimulus, 31, 83, 87, 95, 97, 99 Stomach, 82, 84, 85, 86, 87, 91, 96, 97 Striatum, 51, 98 Stroke, 37, 58, 98 Stupor, 91, 98 Subclinical, 87, 96, 98 Sympathomimetic, 76, 82, 83, 84, 92, 98 Symptomatic, 43, 98 Symptomatic treatment, 43, 98 Synapse, 8, 23, 75, 82, 98, 99 Synapsis, 98 Synaptic, 23, 92, 98 Synaptic Transmission, 92, 98 Syncope, 25, 98 Systemic, 40, 42, 51, 78, 84, 87, 95, 98 Systemic disease, 40, 98 Systolic, 85, 98

105

T Tardive, 80, 98 Teratogenic, 82, 98 Tetracycline, 90, 98 Threshold, 84, 99 Thrombocytopenia, 13, 99 Thrombosis, 98, 99 Tissue, 77, 78, 79, 83, 85, 86, 89, 91, 92, 96, 97, 99 Tolerance, 47, 52, 99 Tomography, 5, 99 Tone, 85, 99 Topical, 41, 49, 50, 84, 99 Toxic, iv, 86, 89, 92, 99 Toxicity, 43, 99 Toxicology, 60, 99 Toxin, 99 Transmitter, 83, 87, 89, 92, 99 Trauma, 78, 85, 99 Tricyclic, 80, 82, 89, 99 Tryptophan, 96, 99 Tunica, 91, 99 Tyrosine, 83, 99 U Ultraviolet radiation, 83, 99 Unconscious, 76, 86, 100 Urethra, 100 Urine, 11, 14, 77, 82, 100 V Vaccine, 75, 94, 100 Valproic Acid, 22, 100 Vascular, 85, 87, 100 Vasoconstriction, 84, 100 Vasodilator, 83, 100 Vein, 87, 100 Venlafaxine, 18, 100 Ventricle, 86, 95, 98, 100 Veterinary Medicine, 59, 100 Virulence, 99, 100 Virus, 43, 75, 87, 100 Vitro, 100 Vivo, 100 X X-ray, 85, 95, 100

106

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Index

107

108

Concerta

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

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